Online wizard for categorising human research projects

Please note: The categoriser can currently not be used for the categorisation of research projects that investigate in vitro diagnostics (IVD). In the meantime, please refer to the infographic and to the case studies until the categoriser is updated.

HRA applicability

Does the research project come under the scope of application of the Human Research Act?
Explanation
The scope of the Human Research Act covers all research concerning human diseases and concerning the structure and function of the human body and involving persons, deceased persons, embryos and foetuses, biological material or health-related data. The Act does not apply to research on embryos in vitro or research with anonymised biological material or anonymously collected or anonymised health-related data. Research refers to the method-driven search for generalisable knowledge. Research concerning diseases means research on the causes, prevention, diagnosis, treatment and epidemiology of impairments of physical and mental health in human beings. Research concerning the structure and function of the human body means basic research, in particular on human anatomy, physiology and genetics, and non-disease-related research concerning interventions and impacts on the human body.
Case studies (8)
Answer

No

Title of study

A large Swiss cohort of patients with inflammatory bowel disease shifts from oral to intravenous iron supplementation therapy over time

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Background

In 2007, leading international experts in the field of inflammatory bowel disease recommended intravenous iron supplements over oral iron supplements because they were more effective and easier to tolerate.

Methods

The Helsana insurance database provided data from adults (aged 18 or older) living in Switzerland, who suffered from Crohn's disease. Helsana is a Swiss health insurance company that covers 18% of the Swiss population (1.2 million individuals). Helsana anonymised data (stripping names, date of birth and address). Data were automatically generated at Helsana quarters, and required no additional manipulation. We analysed the data to determine what percentage of patients with inflammatory bowel disease were prescribed iron therapy, and described the dynamics of intravenous versus oral iron prescription.

Because

This project was based on a study protocol that defines the exact procedures to be used. It included a relatively large number of persons and was not based on individual cases ("method-driven search for generalizable knowledge", defined as research by HRA). The goal was to determine what percentage of patients with inflammatory bowel disease was prescribed iron therapy, and to describe the dynamics of intravenous versus oral iron prescription. The Helsana insurance database provided data from adults who lived in Switzerland and suffered from Crohn's disease ("health-related personal data"). Helsana’s database was automatically generated, and required no additional manipulation. Data were anonymized by an independent institution (Helsana), not involved in the project and separated in time and space. The anonymised database did not include personal identifiers (insurance number, name, date of birth or address). This "research that involves anonymised health-related data" fell outside the scope of HRA.

Answer

Yes

Title of study

Physical activity and energy expenditure across occupational categories

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Background

Physical activity is defined as bodily movements produced by skeletal muscles that result in energy expenditure. This study measured the amount of physical activity, based energy expenditure and other performance criteria that people use during a normal working day. The study focused on differences between occupational categories. The results of this study were used to develope a campaign to prevent sedentary behaviour.

Methods

300 healthy adults (aged 18-65 years), employed full-time in Canton Basel in Switzerland, were enrolled in the study. Participants were stratified by occupational category according to the ISCO-88, and were then grouped into 3 classes (low, middle and high occupational activity). Data on duration of average daily activity, total and active energy expenditure, and daily step counts were collected over 7 consecutive days, using a Sense Wear Mini bracelet (no CE-marking). Participants were asked to wear the Sense Wear Mini bracelet during working hours. The primary outcome was difference in average daily active energy expenditure during working time between the occupational categories.

Because

This project was based on a study protocol that defines the exact procedures to be used. It included a relatively large number of persons and was not based on individual cases ("method-driven search for generalizable knowledge", defined as research by HRA). 300 healthy adults ("persons") employed full-time employed Canton Basel, Switzerland, were asked to register their energy expenditure during working time by wearing a Sense Wear Mini bracelet (no CE-marking). The investigator measured the difference in average daily active energy expenditure during working hours for the different occupational categories, defined according to ISCO-88 ("research concerning the structure and function of the human body").

Answer

No

Title of study

What do physicians think of somatoform disorders?

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Background

Somatoform disorders are characterised by physical symptoms that are not fully explained by a general medical condition. Somatoform disorders are common, but many healthcare workers are confused by the diagnostic terminology and are reluctant to use these diagnostic labels.

Methods

Child psychiatrists, forensic psychiatrists, gastroenterologists, and other physicians from different practice settings were identified through professional societies, like the Academy of Psychosomatic Medicine, American Psychiatric Association, and the American College of Physicians. They were invited to respond to an anonymous Internet survey. By eliciting the views of physicians who see patients with somatoform disorders, we explored their confusion about diagnostic terminology and their reluctance to use these diagnostic labels.

Because

This project was based on a study protocol, in which the exact procedures used to generate generalizable data (method-driven search for generalizable knowledge) were defined. Researchers used a web-based survey to anonymously collect (“anonymously collected data”) data from physicians. The survey contained questions that elicited physicians’ views on disorders that may include physical symptoms not fully explained by a general medical condition. The aim of the study was to explore confusion about diagnostic terminology, and physicians’ reluctance to use these diagnostic labels.

Answer

No

Title of study

Status epilepticus: a possible association with human metapneumovirus infection

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Background

Human metapneumovirus is a relatively new addition to the many viruses that cause respiratory illness in infants and children. Data on the association of human metapneumovirus with neurologic complications is limited.

Methods

In this report, we described two toddlers with human metapneumovirus infection who presented in status epilepticus and went on to develop respiratory failure. Data was collected from the routine hospital health record.

Because

This project was not based on a study protocol, and did not define the exact procedures used to identify and describe the cases. Instead it described two cases identified during routine clinical practice. Thus, it was not "method-driven search for generalizable knowledge". It is not classified as research by the HRA.

Answer

Yes

Title of study

Balance in young female ballet students suffering from chronic knee pain: The effect of physiotherapy with and without a mirror.

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Background

In literature there is general consensus that using a mirror improves proprioception. During rehabilitation, a mirror is very useful for improving stability. In some sports, such as dancing, mirrors are widely used in training. This study evaluated the effectiveness of physiotherapy with mirror on balance in young dancers.

Methods

This study included young dancers (aged 19-25) suffering from chronic knee pain. They were randomly assigned to receive physiotherapy, one to one, with a mirror (mirror- group) or without a mirror (non-mirror group). Their balance was evaluated by BESS (Balance Error Scoring System), which consists of three stances (double limb, single limb, and tandem) on two surfaces (firm and foam). Errors were assessed at each stance and summed to create the two subtotal scores (firm and foam surface) and the final total score (BESS). The BESS was measured at recruitment (T0) and again after 6 months of dance lessons (T1). Primary outcome was difference in total BESS between the groups.

Because

This project was based on a study protocol that defined the exact procedures to be used. It included a relatively large number of persons and was not based on individual cases ("method-driven search for generalizable knowledge", defined as research by HRA). Female dancers ("persons"), between 19-25 years old, suffering from chronic knee pain, were randomly assigned to take ballet lessons with or without a mirror. This study investigated the effect of using a mirror on the dancers’ balance ("research concerning function of the human body").

Answer

Yes

Title of study

Randomized controlled trial in adults with headache recurrence after emergency department discharge, comparing the efficacy of oral sumatriptan to naproxen

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Background

Migraine and other acute primary headaches are treated with a variety of parenteral medications in the emergency department. It is not clear which medication is best to prescribe to primary headache patients when they are discharged. This study compared the efficacy of oral sumatriptan to naproxen for treatment of post-ED recurrent primary headache.

Methods

Adults aged 18 years or older who suffered from headache recurrence after discharge from an emergency department were randomized to either naproxen (Trade®) 500 mg or sumatriptan (Sumatriptan Spirig HC®) 100 mg. This was an open trial: patients and physicians knew who was given which medication. Both products were provided in the original package. The packages had trial-specific labels and were handed out by a hospital pharmacist. Patients were followed-up by telephone 48 hours after emergency department discharge. The primary outcome was change in pain intensity, measured during a two-hour period after ingestion. The change in the group that received 500 mg naproxen (Trade®) was compared to the change in the group that received 100 mg sumatriptan (Sumatriptan Spirig HC®). This difference was measured on a validated 11-point (0–10) verbal Numerical Rating Scale (NRS).

Because

This project was based on a study protocol which defined the exact procedures to be used. The study is designed to answer a disease related research question. It includes a relatively large number of persons and is not based on individual cases ("method-driven search for generalizable knowledge"); thus, it is classified as research according to HRA). Adults (“persons”) who suffered from headache ("research concerning human diseases") after discharge from an emergency department were treated with either 500 mg naproxen (Trade®) or 100 mg sumatriptan (Sumatriptan Spirig HC®).

Project type

Is the research project a project involving living persons?
Explanation
This refers to any research in which a person is directly involved in a research project over a certain period of time (e.g. classical clinical trials), as well as to any research for which biological material is sampled or health-related data are collected for research purposes. On the one hand, this includes projects in which, following the sampling and collection process, the material or personal data are used for answering a scientific question in a correspondingly "specific" research project. Examples include observational studies or research projects with "Phase IV" medicinal products. On the other hand, it also includes projects in which the biological material is sampled or personal data are collected with a view to subsequent, as yet unknown individual research projects. If the research projects are not yet known or described in detail, the phrase "for research purposes" is employed. The material / data are usually stored in a biobank / database or registry, with a view to further use at a later date (as defined in articles 32 and 33 HFG) in connection with a research project yet to be determined.
Case studies (3)
Answer

No

Title of study

Optimal positioning for emergent needle thoracotomy: a cadaver-based study.

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Background

Needle thoracotomy is an emergent procedure designed to relieve tension pneumothorax. The procedure often fails because the needle does not penetrate into the thoracic cavity. Advanced Trauma Life Support guidelines recommend placement in the second intercostal space, midclavicular line, using a 5-cm needle. This study was evaluated placement in the fifth intercostal space, midaxillary line, where tube thoracotomy is routinely performed.

Methods

Twenty unpreserved adult cadavers were evaluated. A standard 14-gauge 5-cm needle was placed in both the fifth intercostal space at the midaxillary line and the traditional second intercostal space at the midclavicular line, in both the right and left chest walls. The needles were secured and thoracotomy was then performed to assess penetration into the pleural cavity. The rate of successful needle placement between fifth intercostal space at the midaxillary line, and the traditional second intercostal space at the midclavicular line on the right and left sites, was compared.

Because

Unpreserved adult cadavers ("deceased persons") were used in this research project.

Answer

Yes

Title of study

Randomized controlled trial in adults with headache recurrence after emergency department discharge, comparing the efficacy of oral sumatriptan to naproxen

Show study
Background

Migraine and other acute primary headaches are treated with a variety of parenteral medications in the emergency department. It is not clear which medication is best to prescribe to primary headache patients when they are discharged. This study compared the efficacy of oral sumatriptan to naproxen for treatment of post-ED recurrent primary headache.

Methods

Adults aged 18 years or older who suffered from headache recurrence after discharge from an emergency department were randomized to either naproxen (Trade®) 500 mg or sumatriptan (Sumatriptan Spirig HC®) 100 mg. This was an open trial: patients and physicians knew who was given which medication. Both products were provided in the original package. The packages had trial-specific labels and were handed out by a hospital pharmacist. Patients were followed-up by telephone 48 hours after emergency department discharge. The primary outcome was change in pain intensity, measured during a two-hour period after ingestion. The change in the group that received 500 mg naproxen (Trade®) was compared to the change in the group that received 100 mg sumatriptan (Sumatriptan Spirig HC®). This difference was measured on a validated 11-point (0–10) verbal Numerical Rating Scale (NRS).

Because

Adults ("persons") who suffered from headache after discharge from an emergency department were included in this research project.

Answer

No

Title of study

The role of satiety mechanisms in genetic risk of obesity (follow-up study).

Show study
Background

Obesity is highly heritable, and researchers are identifying the specific genes involved. Discovering the mechanisms through which obesity-related genes influence weight will help pinpoint novel targets for intervention. This study tested the hypothesis that satiety responsiveness is an intermediate behavioural phenotype associated with genetic predisposition to obesity in children.

Methods

We used genetic data that was collected previously in a population-based twin birth cohort, with twins born in 1996 (National Twins Cohort). In the original cohort study children made up the cohort; one child was randomly selected from each twin pair. Buccal swabs were used to extract DNA. Genome-wide genotyping was done with SNP array, using standard experimental protocols. Children were assigned a unique ID number and the data did not include their names or addresses. We created a polygenic risk score (PRS) comprising 28 common obesity-related single-nucleotide polymorphisms that had been identified in a meta-analysis of obesity-related genome-wide association studies. The primary outcome was the association between the PRS, adiposity, and satiety responsiveness.

Because

We analysed existing genetic data from children, which we collected during a population-based twin birth cohort ("genetic data").

Is the research project a clinical trial?
Explanation
A clinical trial refers to a research project with persons that is designed to investigate the effects of a health-related intervention. To investigate the effects, the principal investigator exposes individuals who have been selected specifically for the trial to the intervention to be investigated in accordance with a protocol that has been approved by the regulatory authorities, and then measures its effects on health or on the structure and function of the human body. Health-related interventions specifically include the administration or use of therapeutic products or other therapeutic measures with the aim of investigating their effects in the prevention, diagnosis, treatment, palliation or rehabilitation of diseases. A clinical trial with a medical device is a systematic investigation of the device involving one or more persons and designed to evaluate the safety or performance of the device. Research projects in which the intervention to be investigated is not used according to a protocol that has been drawn up prospectively, i.e. particularly 'observational studies', are not clinical trials.
Case studies (10)
Answer

Yes

Title of study

Multi-modal effects of thyroid hormone replacement for untreated older adults with subclinical hypothyroidism: a randomised placebo-controlled trial

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Background

Subclinical hypothyroidism is a common condition (81,8%) among older men and women. Thyroid hormone affects many physiological systems, including the vascular tree, heart, skeletal muscle, and brain. Thyroxin is substituted to overcome thyroid hormone deficiency, and may offer multisystem benefits to older people with subclinical hypothyroidism. This multicentre randomised placebo controlled trial aimed to assess the effects of thyroxin replacement in older adults who have persistent subclinical hypothyroidism.

Methods

Men aged ≥65 years, who suffered from subclinical hypothyroidism, were randomized to either a thyroxin (Eltroxin-LF®) starting dose of 50 μg daily p.o. (reduced to 25 μg daily in subjects <50 kg body weight, or if known coronary heart disease) or a matching placebo p.o. Eltroxin-LF®. (The manufacturer of Eltroxin-LF® provided placebo tablets that looked identical.) Subjects were reviewed face-to-face by study nurses at recruitment, study baseline, 6-8 weeks after baseline, after each dose change, 12 months, and annually thereafter. Study nurses made interim telephone contact at 6, 18, 30, and 42 months; possible cardiovascular and serious adverse events were recorded. The primary outcome included fatal and non-fatal cardiovascular events (fatal and non-fatal acute myocardial infarction and stroke; amputations for peripheral vascular disease; revascularisations for atherosclerotic vascular disease, including for acute coronary syndrome; heart failure hospitalisations).

Because

The investigator randomly allocated ("prospectively assigned") men ("persons") who suffered from subclinical hypothyroidism to receive either thyroxin (Eltroxin-LF®) or placebo ("health-related intervention (therapeutic measure)"). The purpose of the study was to compare the number of fatal and non-fatal cardiovascular events ("to investigate its effect on health").

Answer

Yes

Title of study

Randomized controlled trial in adults with headache recurrence after emergency department discharge, comparing the efficacy of oral sumatriptan to naproxen

Show study
Background

Migraine and other acute primary headaches are treated with a variety of parenteral medications in the emergency department. It is not clear which medication is best to prescribe to primary headache patients when they are discharged. This study compared the efficacy of oral sumatriptan to naproxen for treatment of post-ED recurrent primary headache.

Methods

Adults aged 18 years or older who suffered from headache recurrence after discharge from an emergency department were randomized to either naproxen (Trade®) 500 mg or sumatriptan (Sumatriptan Spirig HC®) 100 mg. This was an open trial: patients and physicians knew who was given which medication. Both products were provided in the original package. The packages had trial-specific labels and were handed out by a hospital pharmacist. Patients were followed-up by telephone 48 hours after emergency department discharge. The primary outcome was change in pain intensity, measured during a two-hour period after ingestion. The change in the group that received 500 mg naproxen (Trade®) was compared to the change in the group that received 100 mg sumatriptan (Sumatriptan Spirig HC®). This difference was measured on a validated 11-point (0–10) verbal Numerical Rating Scale (NRS).

Because

In this research project, the investigator randomly assigned ("prospectively assigned") adults ("persons") who suffered from headache after discharge from an emergency department to receive either 500 mg naproxen (Trade®) or 100 mg sumatriptan (Sumatriptan Spirig HC®) ("health related intervention (therapeutic measure)"). The project assessed between-group difference in change in in pain intensity over the 2-hour period after they took the drugs ("to investigate its effect on health").

Answer

No

Title of study

Elderly patients with venous thromboembolism (SWITCO65+): a longitudinal study of the Swiss Cohort

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Background

Venous thromboembolism is common and significantly increases morbidity, mortality, and costs of care. Although most patients with venous thromboembolism are ≥65 years, there is little data on medical outcomes in older patients. We conducted a prospective multicentre cohort study of in- and outpatients ≥65 years, who have acute venous thromboembolism. All five Swiss university and four high-volume non-university hospitals participate in the study. Their goal is to determine the clinical and biological factors and processes of care that drive short- and long-term medical outcomes, health-related quality of life, and use of medical resources in elderly patients with acute venous thromboembolism.

Methods

Elderly patients (≥65 years) with venous thromboembolism were enrolled in the cohort. We followed-up participants from October, 2012, to December, 2013. Follow-up included a telephone interview, two surveillance face-to-face evaluations during the first year, semi-annual contacts, and periodic review of patients' hospital charts. We collected blood samples from all participants at baseline and at 12 months follow-up and established a biobank. We extracted serum, plasma RNA and DNA from the blood. Blood samples were assayed with a standard haematology panel. They were processed and vialed within 1 h of collection and transported in batches to a central laboratory where they were stored at -80°C. The same laboratory analysed all the samples we collected. The primary medical outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism during the follow-up period, defined as new or recurrent pulmonary embolism or deep vein thrombosis (proximal and/or distal).

Because

Researchers used telephone interviews, clinical exams and face-to-face visits to follow up adults ("persons") who suffered from venous thromboembolism. Researchers established a biobank with the blood samples they collected from all participants at enrolment and at 12 months. The study determined the recurrence of symptomatic, objectively confirmed venous thromboembolism during the follow-up period, defined as new or recurrent pulmonary embolism or deep vein thrombosis (proximal and/or distal). This project involved no health-related interventions (according to OClin).

Answer

Yes

Title of study

Balance in young female ballet students suffering from chronic knee pain: The effect of physiotherapy with and without a mirror.

Show study
Background

In literature there is general consensus that using a mirror improves proprioception. During rehabilitation, a mirror is very useful for improving stability. In some sports, such as dancing, mirrors are widely used in training. This study evaluated the effectiveness of physiotherapy with mirror on balance in young dancers.

Methods

This study included young dancers (aged 19-25) suffering from chronic knee pain. They were randomly assigned to receive physiotherapy, one to one, with a mirror (mirror- group) or without a mirror (non-mirror group). Their balance was evaluated by BESS (Balance Error Scoring System), which consists of three stances (double limb, single limb, and tandem) on two surfaces (firm and foam). Errors were assessed at each stance and summed to create the two subtotal scores (firm and foam surface) and the final total score (BESS). The BESS was measured at recruitment (T0) and again after 6 months of dance lessons (T1). Primary outcome was difference in total BESS between the groups.

Because

The investigator randomly assigned ("prospectively assigned") female dancers suffering from chronic knee pain to receive physiotherapy either with or without a mirror. The study assessed between-groups difference via the Balance Error Scoring System ("to investigate its effect on health"). The purpose was to increase our understanding of the use of mirrors during rehabilitation, as a tool to improve stability ("therapeutic measure").

Answer

Yes

Title of study

Effect of and intervention designed to increase physical activity, reduce sedentary behaviour, and increase children’s consumption of fruit and vegetables: Active for Life School Year-based cluster randomised controlled trial.

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Background

This study investigated the effectiveness of a school-based intervention to increase physical activity, reduce sedentary behaviour, and increase children’s consumption of fruit and vegetables.

Methods

Participants were children in school year 4 (age 8-9 years) at recruitment and baseline assessment, and in year 5 during the intervention and follow-up assessments. Schools were randomly allocated to receive either the Active for Life intervention or standard teaching. The Active for Life intervention provided teacher training, lessons, and child-parent interactive homework plans, the materials required for lessons and homework, and written materials for school newsletters and parents. Schools in the control group received standard teaching. Pre-specified primary outcomes were accelerometer assessed minutes of moderate to vigorous physical activity per day, accelerometer assessed minutes of sedentary behaviour per day, and reported daily consumption of servings of fruit and vegetables.

Because

The investigator randomly assigned ("prospectively assigned") primary schools to receive either standard teaching or the Active for Life intervention to increase physical activity, reduce sedentary behaviour, and increase children’s consumption of fruit and vegetables. The study assessed the between-group difference in minutes of moderate to vigorous physical activity per day, minutes of sedentary behaviour per day, and reported daily consumption of servings of fruit and vegetables ("to investigate its effect on health").

Answer

Yes

Title of study

Prospective Evaluation of Etravirine for HIV-infected Patients in Need of Lipid-lowering Drugs

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Background

Dyslipidaemia, characterized by raised triglyceride and low-density lipoprotein cholesterol and reduced high-density lipoprotein cholesterol levels, is common in HIV-infected individuals. Dyslipidaemia has been associated with HIV infection and antiretroviral therapy. This study evaluated the frequency with which the replacement of Lopinavir/Ritonavir, Atazanavir/Nitonavir, Darunavir/Ritonavir or Efavirenz by Etravirin (Intelence®) in dyslipidemic patients with suppressed viremia made it unnecessary to administer statins.

Methods

The study included HIV-infected patients, aged 18-70 years, on statin treatment for at least 3 months, and on a stable (> 3 months) antiretroviral therapy treatment that included at least one of the following drugs: Lopinavir/Ritonavir, Atazanavir/Nitonavir, Darunavir/Ritonavir or Efavirenz. Statin treatment of dyslipidemic HIV patients on antiretroviral drugs was interrupted during 4 weeks. At week 4, patients who qualified for a lipid lowering drug (calculated LDL-C≥ 3mmol/L) replaced lopinavir/ritonavir, atazanavir/ritonavir, darunavir/ritonavir or efavirenz with Etravirine (Intelence®), 400 mg/day, once daily. The primary outcome was the proportion of patients that no longer qualified for statin treatment at 12 weeks (after 8 weeks of Etravirine treatment).

Because

The investigator asked HIV infected adults on statin treatment for at least 3 months, and on a stable antiretroviral therapy treatment, to interrupt their statin treatment for 4 weeks. At week 4, patients who qualified for a lipid lowering drug replaced their antiretroviral treatment with Etravirine (Intelence®), 400 mg/day, once daily ("prospectively assigned"). The study assessed the proportion of patients who no longer qualified for statin treatment after 8 weeks of Etravirine (Intelence®) treatment ("to investigate its effects on health or on the structure and function of the human body").

Answer

Yes

Title of study

Emergency ultrasound-assisted examination of skin and soft tissue infections in the paediatric emergency department.

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Background

This study evaluated the test characteristics of clinical examinations of paediatric patients, supplemented with bedside emergency ultrasound, and compared them to clinical examination alone, to identify skin and soft tissue infections that require drainage. The ultrasound device bears a CE mark, but is not used as intended. Since the bedside emergency ultrasound was added to clinical practice and the investigation of the clinical performance of adding bedside ultrasound was the goal of the study, the study qualifies as a clinical trial (and not as an observational study according to HRO chapter 2). - The study is conducted by an academic sponsor, who does not intend to use the data generated in the study to establish or demonstrate the conformity of the device for the new purpose investigated in the study.

Methods

This was a prospective study of clinical examinations, supplemented with bedside emergency ultrasound, as a diagnostic test to evaluate patients 2 months to 19 years old. These patients were evaluated for skin and soft tissue infections in a paediatric emergency department. Each patient was clinically examined by the responsible physician (standard) and by an independent radiologist, who performed a bedside emergency ultrasound (result not communicated to the responsible physician). The reference standard that determined if a lesion required drainage was defined as "pus expressed at the time of the emergency department visit or within 2 days by follow-up assessment". The primary outcome was the degree of agreement between clinical exam alone, and clinical exam supplemented with ultrasound, on the number of lesions that required drainage within 2 weeks after clinical examination. No other study-related procedures were performed except for the ultrasound.

Because

The performance of an ultrasound device (“medical device”) was systematically tested in children ("persons") aged 2 months to 19 years, who suffered from skin and soft tissue lesions. The goal was to examine how consistent two examination techniques were in diagnosing lesions that require drainage.

Object of study

Is the research project a project with existing biological material or genetic data?
Explanation
These are research projects in which genetic data or biological material are used at a later date. This therefore involves samples / personal data which were sampled / collected previously, e.g. in connection with a treatment or another research project.
Case studies (1)
Answer

Yes

Title of study

The role of satiety mechanisms in genetic risk of obesity (follow-up study).

Show study
Background

Obesity is highly heritable, and researchers are identifying the specific genes involved. Discovering the mechanisms through which obesity-related genes influence weight will help pinpoint novel targets for intervention. This study tested the hypothesis that satiety responsiveness is an intermediate behavioural phenotype associated with genetic predisposition to obesity in children.

Methods

We used genetic data that was collected previously in a population-based twin birth cohort, with twins born in 1996 (National Twins Cohort). In the original cohort study children made up the cohort; one child was randomly selected from each twin pair. Buccal swabs were used to extract DNA. Genome-wide genotyping was done with SNP array, using standard experimental protocols. Children were assigned a unique ID number and the data did not include their names or addresses. We created a polygenic risk score (PRS) comprising 28 common obesity-related single-nucleotide polymorphisms that had been identified in a meta-analysis of obesity-related genome-wide association studies. The primary outcome was the association between the PRS, adiposity, and satiety responsiveness.

Because

We analysed existing genetic data from children, which we collected during a population-based twin birth cohort ("genetic data").

Is the research project a project with existing encoded biological material or genetic data?
Explanation
These are research projects in which genetic data or biological material linked to a specific person via a code are used at a later date. This therefore involves samples / personal data which were sampled / collected previously, e.g. in connection with a treatment or another research project.
Case studies (1)
Answer

Yes

Title of study

The role of satiety mechanisms in genetic risk of obesity (follow-up study).

Show study
Background

Obesity is highly heritable, and researchers are identifying the specific genes involved. Discovering the mechanisms through which obesity-related genes influence weight will help pinpoint novel targets for intervention. This study tested the hypothesis that satiety responsiveness is an intermediate behavioural phenotype associated with genetic predisposition to obesity in children.

Methods

We used genetic data that was collected previously in a population-based twin birth cohort, with twins born in 1996 (National Twins Cohort). In the original cohort study children made up the cohort; one child was randomly selected from each twin pair. Buccal swabs were used to extract DNA. Genome-wide genotyping was done with SNP array, using standard experimental protocols. Children were assigned a unique ID number and the data did not include their names or addresses. We created a polygenic risk score (PRS) comprising 28 common obesity-related single-nucleotide polymorphisms that had been identified in a meta-analysis of obesity-related genome-wide association studies. The primary outcome was the association between the PRS, adiposity, and satiety responsiveness.

Because

We analysed existing genetic data from children, which we collected during a population-based twin birth cohort ("genetic data"). Children were assigned a unique ID number ("existing encoded genetic data") and the data did not include their names or addresses.

Is the research project a project with existing non-coded biological material or genetic data?
Explanation
These are research projects in which genetic personal data or biological material linked to a specific person via unambiguous information are used at a later date. This therefore involves samples / personal data which were sampled / collected previously, e.g. in connection with a treatment or another research project.
Is the research project a project with existing non-genetic health-related data?
Explanation
These are research projects in which non-genetic data are used at a later date. This therefore involves personal data which were collected previously, e.g. in connection with a treatment or another research project.
Case studies (1)
Answer

Yes

Title of study

The prevalence and impact of depression in self-referred clients attending an employee assistance program: a cross-sectional study

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Background

This study determined the prevalence and characteristics of employed adults with depression, who attended an external employee assistance program.

Methods

We obtained data from 9,105 of 10,794 employees suffering from depression who self-referred to an external employee assistance program. The data manager of the assistance program, who was not involved in our project, prepared and provided us with the data. Employees attending the assistance program were coded using a unique identifying number. Data included employees’ age (but not exact date of birth) and language region. Outcome measures included the self-rated nine-item Patient Health Questionnaire (PHQ-9), filled out routinely prior the first counselling visit as part of the assistance program.

Because

Researchers analysed existing data from employed adults who suffered from a first episode of depression and who self-referred to an external employee assistance program. The assistance program collected the data for purposes other than our research project (it was routinely collected in the standard assistance program ["existing health-related data"]).

Is the research project a project with existing encoded, non-genetic data?
Explanation
These are research projects in which non-genetic data linked to a specific person via a code are used at a later date. This therefore involves personal data which were collected previously, e.g. in connection with a treatment or another research project.
Case studies (1)
Answer

Yes

Title of study

The prevalence and impact of depression in self-referred clients attending an employee assistance program: a cross-sectional study

Show study
Background

This study determined the prevalence and characteristics of employed adults with depression, who attended an external employee assistance program.

Methods

We obtained data from 9,105 of 10,794 employees suffering from depression who self-referred to an external employee assistance program. The data manager of the assistance program, who was not involved in our project, prepared and provided us with the data. Employees attending the assistance program were coded using a unique identifying number. Data included employees’ age (but not exact date of birth) and language region. Outcome measures included the self-rated nine-item Patient Health Questionnaire (PHQ-9), filled out routinely prior the first counselling visit as part of the assistance program.

Because

Researchers analysed existing data from employed adults who suffered from a first episode of depression and who self-referred to an external employee assistance program ("existing health-related data"). Participants’ names or other identifying information were not included in the data. Participants were coded with a unique identifying number ("encoded non-genetic data"). The key that linked a subject’s unique identifying number with their personal data was held by the data manager of the assistance program, who was not involved in the research project.

Is the research project a project with existing non-coded, non-genetic data?
Explanation
These are research projects in which non-genetic data linked to a specific person via unambiguous information are used at a later date. This therefore involves personal data which were collected previously, e.g. in connection with a treatment or another research project.
Is the research project a project on deceased people?
Explanation
These are research projects with persons who have been declared dead in accordance with the Transplantation Act and who died less than 70 years ago. It should be noted that research with parts of deceased persons is not considered to be research with biological material within the meaning of article 3 e HFG, but also as research involving deceased persons.
Case studies (1)
Answer

Yes

Title of study

Optimal positioning for emergent needle thoracotomy: a cadaver-based study.

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Background

Needle thoracotomy is an emergent procedure designed to relieve tension pneumothorax. The procedure often fails because the needle does not penetrate into the thoracic cavity. Advanced Trauma Life Support guidelines recommend placement in the second intercostal space, midclavicular line, using a 5-cm needle. This study was evaluated placement in the fifth intercostal space, midaxillary line, where tube thoracotomy is routinely performed.

Methods

Twenty unpreserved adult cadavers were evaluated. A standard 14-gauge 5-cm needle was placed in both the fifth intercostal space at the midaxillary line and the traditional second intercostal space at the midclavicular line, in both the right and left chest walls. The needles were secured and thoracotomy was then performed to assess penetration into the pleural cavity. The rate of successful needle placement between fifth intercostal space at the midaxillary line, and the traditional second intercostal space at the midclavicular line on the right and left sites, was compared.

Because

Unpreserved adult cadavers ("deceased persons") were used in this research project.

Is the research project a project on embryos and fetuses from pregnancy terminations and spontaneous abortions, including stillbirths?
Explanation
These are research projects involving embryos and foetuses from terminations of pregnancy and spontaneous abortions, including stillbirths. A spontaneous abortion is the premature termination of the pregnancy by spontaneous loss of the embryo or foetus weighing less than 500 grams. A stillbirth refers to the death of a child which, after separation from the womb, shows no signs of life and whose weight exceeds this limit. If a child dies immediately after birth – regardless of its weight or age – it counts as a deceased person, and the research on this child is subject to Chapter 5 of HFG.

Observation study: risks for participants

Does the research project involve measures that involve minimal risks and stress for the participating persons?
Explanation
A measure for the sampling of biological material or for collecting health-related personal data with minimal risks and burdens refers to any act on persons which, in all likelihood, is associated with no, or at most mild and transient, physical or psychological effects (including unpleasant social consequences, e.g. a stigmatising effect) for the participating person. This includes, for example, interviews and observations, the collection of peripheral venous or capillary blood samples, small punch biopsies of the skin, the collection or delivery of bodily substances without invasive measures (particularly saliva, urine and stool samples) or smears. It also includes MRI scans without contrast media, ultrasound scans or electrograms. Finally, it also includes investigations with medical devices with conformity marks without contrast media or with authorised medicinal products capable of emitting ionising radiation, provided the effective dose is less than 5 mSv per research project and individual concerned. The risks and burdens should be assessed as objectively as possible, taking account of the specific condition and degree of vulnerability of the participating person, and on the basis of the latest scientific findings.
Case studies (3)
Answer

Yes

Title of study

Rituximab-induced pulmonary function changes: a prospective cohort study

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Background

This study investigated whether rituximab, a drug commonly prescribed to patients with rheumatoid arthritis or inflammatory myositis, was associated with subclinical interstitial lung disease. We measured surrogate markers (by spirometry) of interstitial lung disease before, during and after treatment with rituximab, in patients with rheumatoid arthritis or inflammatory myositis for whom a de novo rituximab treatment was indicated.

Methods

Subjects aged ≥18 years with established diagnosis of rheumatoid arthritis or inflammatory myositis, for whom a de novo rituximab treatment was indicated, were evaluated by spirometry for surrogate markers of interstitial lung disease (forced vital capacity and diffusing capacity of the lung for carbon monoxide). We measured surrogate markers (by spirometry) immediately before initiation of rituximab therapy and 2, 4, 8 weeks and 6 months after initiation of rituximab therapy. We defined a reduction in forced vital capacity of ≥10% or a fall of ≥15% in diffusing capacity of the lung for carbon monoxide as indicative for subclinical interstitial lung disease. The primary outcome was the rate of interstitial lung disease 6 months after treatment with rituximab.

Because

Spirometry is a common test that measures body function. It is non-invasive test; patients blow into a tube. Spirometry poses minimal risk to patients.

Does the research project involve measures that involve more than minimal risks and stress for the participating persons?
Explanation
A measure for the sampling of biological material or for collecting health-related personal data with minimal risks and burdens is any act on persons which, in all likelihood, is associated with no, or at most mild and transient, physical or psychological effects (including unpleasant social consequences, e.g. a stigmatising effect) for the participating person. This includes, for example, interviews and observations, the collection of peripheral venous or capillary blood samples, small punch biopsies of the skin, the collection or delivery of bodily substances without invasive measures (particularly saliva, urine and stool samples) or smears, MRI scans without contrast media, ultrasound scans or electrograms, investigations with medical devices with conformity marks without contrast media or with authorised medicinal products capable of emitting ionising radiation, provided the effective dose is less than 5 mSv per research project and individual concerned. The risks and burdens should be assessed as objectively as possible, taking account of the specific condition and degree of vulnerability of the participating person, and on the basis of the latest scientific findings. If the measures go beyond this level or if, for example, the vulnerability of the participating persons leads to greater risks or burdens, they are considered to be measures associated with more than minimal risks and burdens to the participating person.
Case studies (1)
Answer

Yes

Title of study

Prevalence of cam and pincer-type deformities revealed by hip MRI in asymptomatic young Swiss females: a cross-sectional study

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Background

Femoroacetabular impingement may cause early osteoarthritis (OA) in the non-dysplastic hip. This study determined the prevalence of both femoral and acetabular types of impingement in young females.

Methods

We conducted a population-based cross-sectional study of asymptomatic young females. All participants completed a set of questionnaires and had their hips clinically examined. A random sample of women was subsequently invited for contrast enhanced magnetic resonance images (MRI) of the hip (contrast media injected intra-articularly). MRIs were read to detect cam-type deformities, increased acetabular depths, labral lesions, and impingement pits. We estimated the prevalence of cam-type deformities and increased acetabular depth, and the relationships between deformities and signs of joint damage.

Because

Healthy women completed a questionnaire and had their hips clinically examined. We used magnetic resonance images (MRI) of the hip and contrast agent to determine the prevalence of cam-type deformities in a random sample of participants. Magnetic resonance image and contrast agent are invasive procedures and are more than minimally risky and burdensome for participants.

Typ of intervention

Does the trial involve investigating medicinal products (including combinations according to Art. 2 Para. 1 Letters f and g Medical Device Ordinance (MedDO) from the July 1, 2020)?
Explanation
A medicinal product is a product of chemical or biological origin that is intended to have, or is presented as having, a medicinal effect on the human body, in particular the identification, prevention or treatment of diseases, injuries and handicaps; medicinal products also include blood and blood products. Combinations according to Art. 2 para. 1 let. f and g MedDO are the following products: - Let. f: inseparable combinations of a product intended for dispensing a medicinal product and a medicinal product intended exclusively for use in this combination and which are not reusable; - subparagraph g: Combinations which, when placed on the market or put into service, contain, in addition to the product, as an integral part, a medicinal product which has a principal function.
Case studies (4)
Answer

No

Title of study

Optimal duration of dual antiplatelet therapy after coronary stent implantation

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Background

Patients receiving a coronary stent during a percutaneous corornary intervention need to take dual antiplatelet therapy after the procedure. The aim of the antiplatelet therapy is to prevent patients from stent-related blood clots and other major adverse cardiovascular events following the implantation. Dual antiplatelet therapy consists of regular intake of oral aspirin and a second anti clotting drug. The aim of the study was to evaulate the optimal duration of such a dual antiplatelet therapy.

Methods

Patients undergoing stent placement for the treatment of coronary artery lesions were randomized to receive a prescription for clopidogrel for 12 months or 24 months. In addition, all patients received a prescription for aspirin life-long. Patients were responsible to obtain the prescribed treatment with the prescription at their local pharmacy. Randomized prescriptions specified the International Nonproprietary Name (INN) and therefore left the descision on which specific preparation (proprietary medicinal product) to be handed to the patient at the discretion of the pharmacist. Patients were assessed every 6 months. Patients in the 12-month arm were reminded to stop treatment of clopidogrel at the 12-month visit and patients in the 24-month arm at the 24-month visit. Patients were followed-up for 5 years. The trial had two primary outcomes: 1) the composite of all-cause death and major cardiovasular events at 24-month follow-up; 2) major bleeding events at 24-month follow-up.

Because

Although the effects of different length of clopidogrel treatment are investigated ("medicinal products") in this clinical trial the allocation actually randomized prescriptions. Drugs were not provided by investigators. The choice of the specific preparation (proprietary medicinal product) was left at the discretion of the pharmacist and not documented. Therefore, the trial took a pragmatic, real-world approach and had no direct control on the actual preparation used.

Answer

Yes

Title of study

Randomized trial of behavioural activation and antidepressant medication in the treatment of adolescents with major depression: a randomized trial

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Background

Those diagnosed with depression are overwhelmed by sadness that lasts for at least two weeks. Other symptoms include changes in appetite or sleep patterns, lack of energy or motivation, and even thoughts of suicide. Those diagnosed with depressions often need medication, therapy, or a combination of the two to relieve their symptoms and regain their normal function. This study sought to determine if behavioural activation therapy (a psychological intervention) was as effective as antidepressant medication (fluoxetine) for adolescents diagnosed with depression.

Methods

This study randomly allocated adolescents between 12-16 years old, who met criteria for Major Depressive Disorder, to receive behavioural activation therapy or fluoxetine (Fluoxetin-Mepha®) over the course of 18 weeks. Those randomized to fluoxetine visited their psychiatrist regularly but did not receive psychotherapy. Those who received behavioural activation therapy received between 18-20 one-hour sessions of individual therapy that focused on increasing enjoying and rewarding behaviours. The primary outcome was the difference in mean change of depressive symptoms as measured with the Children's Depression Rating Scale - Revised (CDRS-R).

Because

The effects of behavioural therapy and fluoxetine (Fluoxetin-Mepha®) were investigated (Fluoxetin-Mepha® is a "medicinal product") in this randomised-controlled trial.

Answer

Yes

Title of study

Randomized controlled trial in adults with headache recurrence after emergency department discharge, comparing the efficacy of oral sumatriptan to naproxen

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Background

Migraine and other acute primary headaches are treated with a variety of parenteral medications in the emergency department. It is not clear which medication is best to prescribe to primary headache patients when they are discharged. This study compared the efficacy of oral sumatriptan to naproxen for treatment of post-ED recurrent primary headache.

Methods

Adults aged 18 years or older who suffered from headache recurrence after discharge from an emergency department were randomized to either naproxen (Trade®) 500 mg or sumatriptan (Sumatriptan Spirig HC®) 100 mg. This was an open trial: patients and physicians knew who was given which medication. Both products were provided in the original package. The packages had trial-specific labels and were handed out by a hospital pharmacist. Patients were followed-up by telephone 48 hours after emergency department discharge. The primary outcome was change in pain intensity, measured during a two-hour period after ingestion. The change in the group that received 500 mg naproxen (Trade®) was compared to the change in the group that received 100 mg sumatriptan (Sumatriptan Spirig HC®). This difference was measured on a validated 11-point (0–10) verbal Numerical Rating Scale (NRS).

Because

This clinical trial investigated the effects of naproxen (Trade®) 500 mg and sumatriptan (Sumatriptan Spirig HC®) 100 mg. (Both are "medicinal products").

Is the study investigating a product according to Art. 2a para. 2 Therapeutic Products Act (TPA) (Status from May 26, 2021)?
Explanation
A product according to Art. 2a para. 2 TPA is a product that contains or consists of devitalized human tissue or cells or their derivatives and is not a therapeutic product (i.e. is not a medicinal product according to Art. 4 para. 1 let. a and is not a medical device according to Art. 4 para. 1 let. b TPA), but has a function as a therapeutic product.
Does the trial involve investigating a medical device (in vitro diagnostics excluded) or any other device as defined in Article 1 of the Medical Devices Ordinance of July 1, 2020?
Explanation
A medical device is a product, including instruments, apparatus, devices, in-vitro diagnostics, software, implants, reagents, materials and other articles or substances, that is intended to have, or is presented as having, a medical use, and whose principal effect is not obtained with a medicinal product. In vitro diagnostics are currently still treated separately and do not yet fall under clinical trials with medical devices but under the ClinO. Products according to Article 1 paragraph 1 of the Medical Devices Ordinance (e.g. those without a medical purpose such as purely cosmetic contact lenses) are treated as medical devices.
Case studies (2)
Answer

Yes

Title of study

Percutaneous coronary revascularization: a randomized comparison of a sirolimus-eluting stent with biodegradable polymer and an everolimus-eluting stent with a durable polymer

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Background

Drug-eluting coronary artery stents that release therapeutic agents locally, in a controlled fashion, have improved the safety and efficacy of percutaneous coronary interventions. This study compares the safety and efficacy of a sirolimus-eluting stent with a biodegradable polymer with that of an everolimus-eluting stent with a durable polymer. This is a prospective multicentre randomized controlled non-inferiority trial in patients who underwent percutaneous coronary intervention during routine clinical practice.

Methods

Subjects aged ≥18 years, who have a symptomatic coronary artery disease (including chronic stable angina, silent ischemia, and acute coronary syndromes including NSTE-ACS and STE-ACS), are randomized for treatment either with the CE-marked Orsiro® stent system (sirolimus-eluting stent with a biodegradable polymer) or a CE-marked Xience PRIME® stent system (everolimus-eluting stent with a durable polymer). Primary endpoints are target lesion failure (defined as the composite of cardiac death, as well as target vessel myocardial infarction, and clinically driven target-lesion revascularization). No off-label use and no additional invasive or burdensome procedures in addition to those performed under the normal conditions of use of the two devices are described in the study protocol.

Because

The effects of the Orsiro® stent system and the Xience PRIME® stent system were investigated (both "medical devices") in this clinical trial.

Answer

Yes

Title of study

Emergency ultrasound-assisted examination of skin and soft tissue infections in the paediatric emergency department.

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Background

This study evaluated the test characteristics of clinical examinations of paediatric patients, supplemented with bedside emergency ultrasound, and compared them to clinical examination alone, to identify skin and soft tissue infections that require drainage. The ultrasound device bears a CE mark, but is not used as intended. Since the bedside emergency ultrasound was added to clinical practice and the investigation of the clinical performance of adding bedside ultrasound was the goal of the study, the study qualifies as a clinical trial (and not as an observational study according to HRO chapter 2). - The study is conducted by an academic sponsor, who does not intend to use the data generated in the study to establish or demonstrate the conformity of the device for the new purpose investigated in the study.

Methods

This was a prospective study of clinical examinations, supplemented with bedside emergency ultrasound, as a diagnostic test to evaluate patients 2 months to 19 years old. These patients were evaluated for skin and soft tissue infections in a paediatric emergency department. Each patient was clinically examined by the responsible physician (standard) and by an independent radiologist, who performed a bedside emergency ultrasound (result not communicated to the responsible physician). The reference standard that determined if a lesion required drainage was defined as "pus expressed at the time of the emergency department visit or within 2 days by follow-up assessment". The primary outcome was the degree of agreement between clinical exam alone, and clinical exam supplemented with ultrasound, on the number of lesions that required drainage within 2 weeks after clinical examination. No other study-related procedures were performed except for the ultrasound.

Because

The performance of an ultrasound device (“medical device”) was systematically tested in children ("persons").

Does the trial investigate an intervention that is neither a therapeutic product nor a transplant product, nor a product according to Art. 2a para. 2 Therapeutic Products Act (TPA) (Status from May 26, 2021), nor a transplant?
Explanation
This refers to interventions which are investigated in connection with clinical trials and which are assigned to the participants prospectively on the basis of a protocol. However, the intervention should not be considered to be a therapeutic product as defined in the Therapeutic Products Act, a product according to Art. 2a para. 2 TPA, a transplant product or a transplantation. This therefore refers to trials which investigate medical or other types of health-related methods or procedures, for example those used in surgery, physiotherapy, occupational therapy or other areas such as psychiatry and psychotherapy. This includes, on the one hand, all manual activities or procedures, even if carried out with instruments, although these instruments are not themselves the subject of the research (e.g. nursing measures, surgical or massage techniques). On the other hand, they include linguistic interventions, e.g. instructions or guides, or certain natural or artificial environmental conditions to which a person is specifically exposed. The context in which an intervention is used in the clinical trial determines its status. Thus, an everyday activity (e.g. sunbathing) can become a clinical intervention through its method-driven application in the research (for example in depression).
Case studies (4)
Answer

Yes

Title of study

Optimal duration of dual antiplatelet therapy after coronary stent implantation

Show study
Background

Patients receiving a coronary stent during a percutaneous corornary intervention need to take dual antiplatelet therapy after the procedure. The aim of the antiplatelet therapy is to prevent patients from stent-related blood clots and other major adverse cardiovascular events following the implantation. Dual antiplatelet therapy consists of regular intake of oral aspirin and a second anti clotting drug. The aim of the study was to evaulate the optimal duration of such a dual antiplatelet therapy.

Methods

Patients undergoing stent placement for the treatment of coronary artery lesions were randomized to receive a prescription for clopidogrel for 12 months or 24 months. In addition, all patients received a prescription for aspirin life-long. Patients were responsible to obtain the prescribed treatment with the prescription at their local pharmacy. Randomized prescriptions specified the International Nonproprietary Name (INN) and therefore left the descision on which specific preparation (proprietary medicinal product) to be handed to the patient at the discretion of the pharmacist. Patients were assessed every 6 months. Patients in the 12-month arm were reminded to stop treatment of clopidogrel at the 12-month visit and patients in the 24-month arm at the 24-month visit. Patients were followed-up for 5 years. The trial had two primary outcomes: 1) the composite of all-cause death and major cardiovasular events at 24-month follow-up; 2) major bleeding events at 24-month follow-up.

Because

Although the effects of different length of clopidogrel treatment are investigated ("medicinal products") in this clinical trial the allocation actually randomized prescriptions. Drugs were not provided by investigators. The choice of the specific preparation (proprietary medicinal product) was left at the discretion of the pharmacist and not documented. Therefore, the trial took a pragmatic, real-world approach and had no direct control on the actual preparation used.

Answer

Yes

Title of study

Randomized trial of behavioural activation and antidepressant medication in the treatment of adolescents with major depression: a randomized trial

Show study
Background

Those diagnosed with depression are overwhelmed by sadness that lasts for at least two weeks. Other symptoms include changes in appetite or sleep patterns, lack of energy or motivation, and even thoughts of suicide. Those diagnosed with depressions often need medication, therapy, or a combination of the two to relieve their symptoms and regain their normal function. This study sought to determine if behavioural activation therapy (a psychological intervention) was as effective as antidepressant medication (fluoxetine) for adolescents diagnosed with depression.

Methods

This study randomly allocated adolescents between 12-16 years old, who met criteria for Major Depressive Disorder, to receive behavioural activation therapy or fluoxetine (Fluoxetin-Mepha®) over the course of 18 weeks. Those randomized to fluoxetine visited their psychiatrist regularly but did not receive psychotherapy. Those who received behavioural activation therapy received between 18-20 one-hour sessions of individual therapy that focused on increasing enjoying and rewarding behaviours. The primary outcome was the difference in mean change of depressive symptoms as measured with the Children's Depression Rating Scale - Revised (CDRS-R).

Because

The effects of behavioural therapy and fluoxetine (Fluoxetin-Mepha®) were investigated (Fluoxetin-Mepha® is a "medicinal product") in this randomised-controlled trial. Behavioural therapy (psychotherapy) is not a medicinal product/device, a transplant or transplant product, a gene therapy, or a pathogenic organism.

Answer

Yes

Title of study

Effect of and intervention designed to increase physical activity, reduce sedentary behaviour, and increase children’s consumption of fruit and vegetables: Active for Life School Year-based cluster randomised controlled trial.

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Background

This study investigated the effectiveness of a school-based intervention to increase physical activity, reduce sedentary behaviour, and increase children’s consumption of fruit and vegetables.

Methods

Participants were children in school year 4 (age 8-9 years) at recruitment and baseline assessment, and in year 5 during the intervention and follow-up assessments. Schools were randomly allocated to receive either the Active for Life intervention or standard teaching. The Active for Life intervention provided teacher training, lessons, and child-parent interactive homework plans, the materials required for lessons and homework, and written materials for school newsletters and parents. Schools in the control group received standard teaching. Pre-specified primary outcomes were accelerometer assessed minutes of moderate to vigorous physical activity per day, accelerometer assessed minutes of sedentary behaviour per day, and reported daily consumption of servings of fruit and vegetables.

Because

The study asked if the Active for Life intervention increased physical activity, reduced sedentary behaviour, and increased children’s fruit and vegetable more than standard teaching did. A teaching intervention is not a medicinal product or device, a transplant or transplant product, a gene therapy, or a pathogenic organism.

Does the trial investigate a transplant product?
Explanation
Transplant products are products obtained from human or animal organs, tissues or cells that can be standardised, or whose production processes can be standardised. On the basis of the definitions of terms and the distinctions that are currently being discussed in the EU, Swissmedic (in consultation with the FOPH) interprets this description as follows: "A transplant product (TxP) is a product that is used in, or administered to, human beings and that consists of, or contains, autologous, allogeneic or xenogeneic vital organs, tissues or cells produced by means of standardised processes. These organs, tissues or cells concerned have usually undergone substantial manipulation so as to influence their original biological characteristics, physiological functions or structural properties (according to the definition in Annex 1 to the proposal of 23 May 2007 for an EU regulation on advanced therapy medicinal products). Transplant products are products obtained from human or animal organs, tissues or cells that can be standardised, or whose production processes can be standardised. On the basis of the definitions of terms and the distinctions that are currently being discussed in the EU, Swissmedic (in consultation with the FOPH) interprets this description as follows: "A transplant product (TxP) is a product that is used in, or administered to, human beings and that consists of, or contains, autologous, allogeneic or xenogeneic vital organs, tissues or cells produced by means of standardised processes. These organs, tissues or cells concerned have usually undergone substantial manipulation so as to influence their original biological characteristics, physiological functions or structural properties (according to the definition in Annex 1 to the proposal of 23 May 2007 for an EU regulation on advanced therapy medicinal products).
Does the trial investigate gene therapy or a pathogenic organism?
Explanation
Clinical trials of gene therapy refer to those trials in which the introduction of genetic material into somatic human cells (in- and ex-vivo) for therapeutic purposes is investigated in respect of its effects. This also includes those clinical trials in which genetically modified organisms, particularly replication-competent viruses, are investigated as medicinal products, in accordance with the Release Ordinance (FrSV). Biologically active genetic material refers to DNA and RNA sequences that are incapable of replicating independently (e.g. plasmids), but can be transmitted, have a pathogenic effect, or are infectious or generally capable of causing a targeted or foreseeable effect in an organism, such as protein expression, immune response or inhibition of cell division. These may be genetically modified. In FrSV, biologically active genetic material is equated with microorganisms. Ultimately, it therefore refers to those clinical trials which investigate the effects of pathogenic organisms as medicinal products for the prevention or treatment of diseases. According to FrSV, pathogenic organisms are organisms that can cause diseases in human beings, domesticated animals and plants, in wild flora or fauna or other organisms. Clinical trials of gene therapy refer to those trials in which the introduction of genetic material into somatic human cells (in- and ex-vivo) for therapeutic purposes is investigated in respect of its effects. This also includes those clinical trials in which genetically modified organisms, particularly replication-competent viruses, are investigated as medicinal products, in accordance with the Release Ordinance (FrSV). Biologically active genetic material refers to DNA and RNA sequences that are incapable of replicating independently (e.g. plasmids), but can be transmitted, have a pathogenic effect, or are infectious or generally capable of causing a targeted or foreseeable effect in an organism, such as protein expression, immune response or inhibition of cell division. These may be genetically modified. In FrSV, biologically active genetic material is equated with microorganisms. Ultimately, it therefore refers to those clinical trials which investigate the effects of pathogenic organisms as medicinal products for the prevention or treatment of diseases. According to FrSV, pathogenic organisms are organisms that can cause diseases in human beings, domesticated animals and plants, in wild flora or fauna or other organisms.

Medicinal product: status of market authorization

Is the IMP authorised in Switzerland?
Explanation
A medicinal product is considered to be authorised if it has been authorised by the Swiss Agency for Therapeutic Products (Swissmedic) for placing on the market in Switzerland (distribution and dispensing). Authorised medicinal products can be viewed on the Swissmedic website (http://www.swissmedicinfo.ch/).A medicinal product is considered to be authorised if it has been authorised by the Swiss Agency for Therapeutic Products (Swissmedic) for placing on the market in Switzerland (distribution and dispensing). Authorised medicinal products can be viewed on the Swissmedic website (http://www.swissmedicinfo.ch/).
Case studies (3)
Answer

Yes

Title of study

Symptomatic therapy for uncomplicated lower urinary tract infections in an ambulatory setting: a randomized, double-blind trial

Show study
Background

Most urinary tract infections are uncomplicated. The disease is benign and self-limited, and the primary goal of treatment is symptom relief rather than cure. The study was designed to determine if initial symptomatic treatment, followed by optional delayed antibiotic treatment, was non-inferior to immediate antibiotic treatment, followed by optional delayed antibiotic treatment, in resolving symptoms.

Methods

Women 18-70 years old, who had acute uncomplicated urinary tract infections, were randomly allocated to receive symptomatic treatment (diclofenac [Olfen®] 75 mg twice daily, followed by optional, delayed antibiotic treatment with a single dose of 3 g fosfomycin, if the patient thought it was necessary) or to receive immediate antibiotic treatment (norfloxacin [Norfloxacin-Teva®] 400 mg twice daily, for three days, followed by optional, delayed antibiotic treatment with single dose of 3 g fosfomycin if the patient thought it was necessary). To ensure blinding, Olfen® and Norfloxacin-Teva® were encapsulated in a GMP-facility by a pharmacist. Patients kept a diary for 10 days, in which they described symptoms. The researchers followed up with a telephone interview on days 10 and 30. The primary outcome of the trial was the proportion of patients whose symptoms resolved on day 4.

Because

This randomized-controlled, double-blind trial investigated the effects of diclofenac (Olfen®) and norfloxacin (Norfloxacin-Teva®), which are "medicinal products"). Both are "authorised" for the Swiss market (approval number for Olfen®: 55164 (Swissmedic) and Norfloxacin-Teva®: 55602 (Swissmedic)).

Answer

No

Title of study

A comparison of the efficacy of secukinumab and ustekinumab in patients with plaque-type psoriasis: a randomized-controlled trial.

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Background

This study compared the efficacy of secukinumab to ustekinumab (Stelara®) in patients that have plaque-type psoriasis.

Methods

Adults, aged 18 or older, who suffered from moderate to severe plaque type psoriasis for at least 6 months before randomization, were randomly allocated to receive secukinumab 300 mg once every weeks (at weeks 0, 1, 2, 3), followed by monthly dosing starting at week 4 and continuing through week 48, or to receive ustekinumab (Stelara®) 45mg once a week (at weeks 0, 4, 8 and 12). Severity and extent of psoriasis was measured using the PASI score (Psoriasis Area and Severity Index). Primary outcome was the difference in the proportion of PASI 90 responders after 16 weeks.

Because

The effects of secukinumab and ustekinumab (Stelara®) were investigated in this clinical trial. Ustekinumab (Stelara®) is "authorised" for the Swiss market (approval number Stelara®: 61267 [Swissmedic]). However, secukinumab does not have a marketing authorisation in Switzerland.

Answer

Yes

Title of study

Randomized controlled trial in adults with headache recurrence after emergency department discharge, comparing the efficacy of oral sumatriptan to naproxen

Show study
Background

Migraine and other acute primary headaches are treated with a variety of parenteral medications in the emergency department. It is not clear which medication is best to prescribe to primary headache patients when they are discharged. This study compared the efficacy of oral sumatriptan to naproxen for treatment of post-ED recurrent primary headache.

Methods

Adults aged 18 years or older who suffered from headache recurrence after discharge from an emergency department were randomized to either naproxen (Trade®) 500 mg or sumatriptan (Sumatriptan Spirig HC®) 100 mg. This was an open trial: patients and physicians knew who was given which medication. Both products were provided in the original package. The packages had trial-specific labels and were handed out by a hospital pharmacist. Patients were followed-up by telephone 48 hours after emergency department discharge. The primary outcome was change in pain intensity, measured during a two-hour period after ingestion. The change in the group that received 500 mg naproxen (Trade®) was compared to the change in the group that received 100 mg sumatriptan (Sumatriptan Spirig HC®). This difference was measured on a validated 11-point (0–10) verbal Numerical Rating Scale (NRS).

Because

This clinical trial investigated the effects of naproxen (Trade®) 500 mg and sumatriptan (Sumatriptan Spirig HC®) 100 mg. Both are “authorised” for the market in Switzerland, and are provided “as is”, unchanged except for their labels. (Approval numbers for sumatriptan/[Sumatriptan Spirig HC®]: 58466, 58512, 58513 [Swissmedic]; and, for naproxen/[Trade®]: 51480 [Swissmedic]).

PDF summary
Is a placebo used in the trial, or is the original status of the medicinal product or its packaging as approved by Swissmedic modified?
Explanation
The authorisation of a medicinal product by the Swiss Agency for Therapeutic Products (Swissmedic) includes its manufacture (incl. method, labelling, packaging, etc.), the medicinal product information and the type of dispensing and use. If the original state (e.g. pharmaceutical form, composition, packaging, labelling, etc.) of the medicinal product, as authorised by Swissmedic, is changed, the question must be answered with Yes. If a placebo that is not authorised by Swissmedic for this type of use is used in connection with the clinical trial, the question must likewise be answered with Yes. The authorisation of a medicinal product by the Swiss Agency for Therapeutic Products (Swissmedic) includes its manufacture (incl. method, labelling, packaging, etc.), the medicinal product information and the type of dispensing and use. If the original state (e.g. pharmaceutical form, composition, packaging, labelling, etc.) of the medicinal product, as authorised by Swissmedic, is changed, the question must be answered with Yes. If a placebo that is not authorised by Swissmedic for this type of use is used in connection with the clinical trial, the question must likewise be answered with Yes.
Case studies (5)
Answer

No

Title of study

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study

Show study
Background

The androgen receptor inhibitor enzalutamide (Xtandi®) was approved to treat metastatic castration-resistant prostate cancer that has progressed on docetaxel. This study assessed the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer.

Methods

Men at least 18 years old, with hormone-naive prostate cancer, for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide (Xtandi®) 160 mg/day. The primary outcome, measured at week 25, was the proportion of patients in whom a prostate-specific antigen had declined 80% or more.

Because

This clinical trial investigated the effects of enzalutamide (Xtandi®) 160 mg/day. Xtandi® is “authorised” for the market in Switzerland, and is provided “as is”. The medicinal product was provided in its original package but labelled with a trial-specific sticker (label). However, the label did not cover any pharmaceutically relevant information.

Answer

Yes

Title of study

Symptomatic therapy for uncomplicated lower urinary tract infections in an ambulatory setting: a randomized, double-blind trial

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Background

Most urinary tract infections are uncomplicated. The disease is benign and self-limited, and the primary goal of treatment is symptom relief rather than cure. The study was designed to determine if initial symptomatic treatment, followed by optional delayed antibiotic treatment, was non-inferior to immediate antibiotic treatment, followed by optional delayed antibiotic treatment, in resolving symptoms.

Methods

Women 18-70 years old, who had acute uncomplicated urinary tract infections, were randomly allocated to receive symptomatic treatment (diclofenac [Olfen®] 75 mg twice daily, followed by optional, delayed antibiotic treatment with a single dose of 3 g fosfomycin, if the patient thought it was necessary) or to receive immediate antibiotic treatment (norfloxacin [Norfloxacin-Teva®] 400 mg twice daily, for three days, followed by optional, delayed antibiotic treatment with single dose of 3 g fosfomycin if the patient thought it was necessary). To ensure blinding, Olfen® and Norfloxacin-Teva® were encapsulated in a GMP-facility by a pharmacist. Patients kept a diary for 10 days, in which they described symptoms. The researchers followed up with a telephone interview on days 10 and 30. The primary outcome of the trial was the proportion of patients whose symptoms resolved on day 4.

Because

This randomized-controlled, double-blind trial investigated the effects of diclofenac (Olfen®) and norfloxacin (Norfloxacin-Teva®), which are "medicinal products"). Both are "authorised" for the Swiss market. Neither product was provided in the original state (authorised), but were encapsulated instead.

Answer

Yes

Title of study

Multi-modal effects of thyroid hormone replacement for untreated older adults with subclinical hypothyroidism: a randomised placebo-controlled trial

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Background

Subclinical hypothyroidism is a common condition (81,8%) among older men and women. Thyroid hormone affects many physiological systems, including the vascular tree, heart, skeletal muscle, and brain. Thyroxin is substituted to overcome thyroid hormone deficiency, and may offer multisystem benefits to older people with subclinical hypothyroidism. This multicentre randomised placebo controlled trial aimed to assess the effects of thyroxin replacement in older adults who have persistent subclinical hypothyroidism.

Methods

Men aged ≥65 years, who suffered from subclinical hypothyroidism, were randomized to either a thyroxin (Eltroxin-LF®) starting dose of 50 μg daily p.o. (reduced to 25 μg daily in subjects <50 kg body weight, or if known coronary heart disease) or a matching placebo p.o. Eltroxin-LF®. (The manufacturer of Eltroxin-LF® provided placebo tablets that looked identical.) Subjects were reviewed face-to-face by study nurses at recruitment, study baseline, 6-8 weeks after baseline, after each dose change, 12 months, and annually thereafter. Study nurses made interim telephone contact at 6, 18, 30, and 42 months; possible cardiovascular and serious adverse events were recorded. The primary outcome included fatal and non-fatal cardiovascular events (fatal and non-fatal acute myocardial infarction and stroke; amputations for peripheral vascular disease; revascularisations for atherosclerotic vascular disease, including for acute coronary syndrome; heart failure hospitalisations).

Because

The effects of thyroxin (Eltroxin-LF®) and placebo were investigated in this clinical trial. Eltroxin-LF® is "authorised" for the Swiss market. The placebo was manufactured specifically for this research project. Aspects related to good manufacturing practice need to be checked by Swissmedic.

Answer

No

Title of study

Randomized controlled trial in adults with headache recurrence after emergency department discharge, comparing the efficacy of oral sumatriptan to naproxen

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Background

Migraine and other acute primary headaches are treated with a variety of parenteral medications in the emergency department. It is not clear which medication is best to prescribe to primary headache patients when they are discharged. This study compared the efficacy of oral sumatriptan to naproxen for treatment of post-ED recurrent primary headache.

Methods

Adults aged 18 years or older who suffered from headache recurrence after discharge from an emergency department were randomized to either naproxen (Trade®) 500 mg or sumatriptan (Sumatriptan Spirig HC®) 100 mg. This was an open trial: patients and physicians knew who was given which medication. Both products were provided in the original package. The packages had trial-specific labels and were handed out by a hospital pharmacist. Patients were followed-up by telephone 48 hours after emergency department discharge. The primary outcome was change in pain intensity, measured during a two-hour period after ingestion. The change in the group that received 500 mg naproxen (Trade®) was compared to the change in the group that received 100 mg sumatriptan (Sumatriptan Spirig HC®). This difference was measured on a validated 11-point (0–10) verbal Numerical Rating Scale (NRS).

Because

This clinical trial investigated the effects of naproxen (Trade®) 500 mg and sumatriptan (Sumatriptan Spirig HC®) 100 mg. Both are “authorised” for the market in Switzerland, and are provided “as is”. The medicinal product was provided in its original package but labelled with a trial-specific sticker (label). However, the label did not cover any pharmaceutically relevant information. This modification is not manufactering according to the Therapeutics Product Act (TPA).

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Medicinal product: administration

Does the IMP administration comply with the specifications in the summary of product characteristics (SPC)?
Explanation
The medicinal product to be investigated will be used in connection with the clinical trial in accordance with the provisions of the Information for healthcare professionals approved by Swissmedic, if the application specifications in the Information for healthcare professionals are observed in respect of the indications, dosage, pharmaceutical form and patient group.The medicinal product to be investigated will be used in connection with the clinical trial in accordance with the provisions of the Information for healthcare professionals approved by Swissmedic, if the application specifications in the Information for healthcare professionals are observed in respect of the indications, dosage, pharmaceutical form and patient group.
Case studies (2)
Answer

No

Title of study

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study

Show study
Background

The androgen receptor inhibitor enzalutamide (Xtandi®) was approved to treat metastatic castration-resistant prostate cancer that has progressed on docetaxel. This study assessed the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer.

Methods

Men at least 18 years old, with hormone-naive prostate cancer, for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide (Xtandi®) 160 mg/day. The primary outcome, measured at week 25, was the proportion of patients in whom a prostate-specific antigen had declined 80% or more.

Because

This clinical trial investigated the effects of enzalutamide (Xtandi®) 160 mg/day in men aged 18 or older with hormone-naive prostate cancer, for whom hormone therapy was indicated and who had non-castration levels of testosterone. Enzalutamide (Xtandi®) was not given in combination with hormone therapy. Enzalutamide (Xtandi®) is approved in combination with luteinising hormone-releasing hormone analogues to treat patients with metastatic castration-resistant prostate cancer, who already received docetaxel therapy. Use of enzalutamide (Xtandi®) within this clinical trial does not correspond with approved uses.

PDF summary
Does the deviation from the specifications in the SPC concern indication or dosage?
Explanation
The use of the medicinal product to be investigated deviates from the specifications stated in the Information for healthcare professionals only in respect of the indications or specified dosages. If, during the use of the medicinal product, the pharmaceutical form differs from that specified in the Information for healthcare professionals, the question must be answered with No. The use of the medicinal product to be investigated deviates from the specifications stated in the Information for healthcare professionals only in respect of the indications or specified dosages. If, during the use of the medicinal product, the pharmaceutical form differs from that specified in the Information for healthcare professionals, the question must be answered with No.
Case studies (1)

Medicinal product: indication

Does the indication lie within the same disease group in the ICD-10 classification as stated in the SPC (disease group indicated by the three-digit code)?
Explanation
The use of the medicinal product to be investigated deviates minimally, at most, from the indications cited in the Information for healthcare professionals, if the disease to be treated in connection with the clinical trial belongs to the same indication group to which the indications cited in the Information for healthcare professionals are also assigned. The indication group is defined by the three-character code of the single axis and mono-hierarchical classification system known as the "International Statistical Classification of Diseases and related Health Problems" ICD-10 (http://apps.who.int/classifications/icd10/browse/2010/en), for the indication forming the focus of the clinical trial. The risks and burdens for the participants associated with the use of the medicinal product in connection with the clinical trial for an indication that can be assigned to the same indication group as at least one indication specified in the Information for healthcare professionals, remain comparable with those associated with the use for an authorised indication. This should be substantiated in terms of its proximity to the standard treatment / authorised use of the medicinal product. The use of the medicinal product to be investigated deviates minimally, at most, from the indications cited in the Information for healthcare professionals, if the disease to be treated in connection with the clinical trial belongs to the same indication group to which the indications cited in the Information for healthcare professionals are also assigned. The indication group is defined by the three-character code of the single axis and mono-hierarchical classification system known as the "International Statistical Classification of Diseases and related Health Problems" ICD-10 (http://apps.who.int/classifications/icd10/browse/2010/en), for the indication forming the focus of the clinical trial. The risks and burdens for the participants associated with the use of the medicinal product in connection with the clinical trial for an indication that can be assigned to the same indication group as at least one indication specified in the Information for healthcare professionals, remain comparable with those associated with the use for an authorised indication. This should be substantiated in terms of its proximity to the standard treatment / authorised use of the medicinal product.
Case studies (2)
Answer

Yes

Title of study

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study

Show study
Background

The androgen receptor inhibitor enzalutamide (Xtandi®) was approved to treat metastatic castration-resistant prostate cancer that has progressed on docetaxel. This study assessed the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer.

Methods

Men at least 18 years old, with hormone-naive prostate cancer, for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide (Xtandi®) 160 mg/day. The primary outcome, measured at week 25, was the proportion of patients in whom a prostate-specific antigen had declined 80% or more.

Because

This clinical trial investigates the effects of enzalutamide (Xtandi®) 160 mg/day in men aged 18 or older with hormone-naive prostate cancer, for whom hormone therapy was indicated and who had non-castration levels of testosterone. Xtandi® is approved in combination with luteinising hormone-releasing hormone analogues to treat patients with metastatic castration-resistant prostate cancer, who have already received docetaxel therapy. Hormone-naive prostate cancer falls within the same ICD-10 group as the approved indication (metastatic castration-resistant prostate cancer, for those who have previously received docetaxel therapy C61: Malignant neoplasm of prostate).

Medicinal product: dosage

Is the disease for which the IMP is administered in the clinical trial a self-limiting disease or condition?
Explanation
A disease is described as self-limiting if the sufferer recovers spontaneously or without therapeutic measures.A disease is described as self-limiting if the sufferer recovers spontaneously or without therapeutic measures.
Case studies (2)
Answer

No

Title of study

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study

Show study
Background

The androgen receptor inhibitor enzalutamide (Xtandi®) was approved to treat metastatic castration-resistant prostate cancer that has progressed on docetaxel. This study assessed the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer.

Methods

Men at least 18 years old, with hormone-naive prostate cancer, for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide (Xtandi®) 160 mg/day. The primary outcome, measured at week 25, was the proportion of patients in whom a prostate-specific antigen had declined 80% or more.

Because

This clinical trial investigates the effects of enzalutamide (Xtandi®) 160 mg/day in men aged 18 or older with hormone-naive prostate cancer, for whom hormone therapy was indicated and who had non-castration levels of testosterone. Self-limiting diseases resolve spontaneously, with or without treatment. Untreated hormone-naive prostate cancer does not resolve spontaneously.

Answer

No

Title of study

Randomized trial of behavioural activation and antidepressant medication in the treatment of adolescents with major depression: a randomized trial

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Background

Those diagnosed with depression are overwhelmed by sadness that lasts for at least two weeks. Other symptoms include changes in appetite or sleep patterns, lack of energy or motivation, and even thoughts of suicide. Those diagnosed with depressions often need medication, therapy, or a combination of the two to relieve their symptoms and regain their normal function. This study sought to determine if behavioural activation therapy (a psychological intervention) was as effective as antidepressant medication (fluoxetine) for adolescents diagnosed with depression.

Methods

This study randomly allocated adolescents between 12-16 years old, who met criteria for Major Depressive Disorder, to receive behavioural activation therapy or fluoxetine (Fluoxetin-Mepha®) over the course of 18 weeks. Those randomized to fluoxetine visited their psychiatrist regularly but did not receive psychotherapy. Those who received behavioural activation therapy received between 18-20 one-hour sessions of individual therapy that focused on increasing enjoying and rewarding behaviours. The primary outcome was the difference in mean change of depressive symptoms as measured with the Children's Depression Rating Scale - Revised (CDRS-R).

Because

The effects of behavioural therapy and fluoxetine (Fluoxetin-Mepha®) were investigated in this randomized-controlled trial, which included adolescents between 12-16 years old, who suffered from major depressive disorder. A self-limiting disease is one that resolves spontaneously, with or without specific treatment. Major depression disorder is not considered a self-limiting disease. (The estimated remission rate of untreated major depression within 12 months is about 50%, though the rates may be higher in adolescents [Whiteford HA et al. Psychol Med 2013; 43: 1569-85]).

Is the dosage lower than specified in the SPC?
Explanation
- -

Medicinal product: medical standard

Does the IMP's administration comply with standard medical practice as defined in a treatment guideline developed in accordance with international quality critieria?
Explanation
A use of the medicinal product to be investigated corresponds to a medical standard if it is presented as standard in a guideline drafted in accordance with internationally recognised quality criteria. Standardised uses of medicinal products are described in medical (therapeutic) guidelines (clinical practice guidelines) in respect of benefit, safety and effectiveness. If the use of the medicinal product in the clinical trial meets the requirements stated in a broadly supported, evidence-based guideline, it can be assumed that the risk of the intervention to be investigated is comparable with the risk of the standard treatment that is normally employed in medical practice. In recent decades, established quality standards have emerged which are intended to form the basis for the drafting of medical guidelines in order for these to be recognised internationally in medical practice. These include "AGREE II" (Appraisal of Guidelines for Research and Evaluation) for the development of guidelines and the evaluation of the methodological stringency and transparency with which a guideline was developed. This instrument is now used by many international organisations and is recommended by WHO for the development and evaluation of guidelines. Numerous guidelines in various disciplines have been investigated for their quality and described in the scientific literature with the aid of this tool. Recently, at the request of the US Congress, the American Institute of Medicine (IOM) of the National Academies refined the standards for medical guidelines on the basis of AGREE II, and specifically addressed certain aspects, for example the management of conflicts of interest, the funding of the preparation of the guideline and the requirement for systematic reviewing of existing evidence. A use of the medicinal product to be investigated corresponds to a medical standard if it is presented as standard in a guideline drafted in accordance with internationally recognised quality criteria. Standardised uses of medicinal products are described in medical (therapeutic) guidelines (clinical practice guidelines) in respect of benefit, safety and effectiveness. If the use of the medicinal product in the clinical trial meets the requirements stated in a broadly supported, evidence-based guideline, it can be assumed that the risk of the intervention to be investigated is comparable with the risk of the standard treatment that is normally employed in medical practice. In recent decades, established quality standards have emerged which are intended to form the basis for the drafting of medical guidelines in order for these to be recognised internationally in medical practice. These include "AGREE II" (Appraisal of Guidelines for Research and Evaluation) for the development of guidelines and the evaluation of the methodological stringency and transparency with which a guideline was developed. This instrument is now used by many international organisations and is recommended by WHO for the development and evaluation of guidelines. Numerous guidelines in various disciplines have been investigated for their quality and described in the scientific literature with the aid of this tool. Recently, at the request of the US Congress, the American Institute of Medicine (IOM) of the National Academies refined the standards for medical guidelines on the basis of AGREE II, and specifically addressed certain aspects, for example the management of conflicts of interest, the funding of the preparation of the guideline and the requirement for systematic reviewing of existing evidence.
Case studies (2)
Answer

Yes

Title of study

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study

Show study
Background

The androgen receptor inhibitor enzalutamide (Xtandi®) was approved to treat metastatic castration-resistant prostate cancer that has progressed on docetaxel. This study assessed the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer.

Methods

Men at least 18 years old, with hormone-naive prostate cancer, for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide (Xtandi®) 160 mg/day. The primary outcome, measured at week 25, was the proportion of patients in whom a prostate-specific antigen had declined 80% or more.

Because

This clinical trial investigates the effects of enzalutamide (Xtandi®) 160 mg/day in men aged 18 or older with hormone-naive prostate cancer, for whom hormone therapy was indicated and who had non-castration levels of testosterone. Xtandi® was not be given in combination with hormone therapy. Thus it does not comply with the intended use recommended by the European Association of Urology guidelines on prostate cancer (treatment guideline developed in accordance with international quality criteria).

PDF summary
Answer

No

Title of study

Randomized trial of behavioural activation and antidepressant medication in the treatment of adolescents with major depression: a randomized trial

Show study
Background

Those diagnosed with depression are overwhelmed by sadness that lasts for at least two weeks. Other symptoms include changes in appetite or sleep patterns, lack of energy or motivation, and even thoughts of suicide. Those diagnosed with depressions often need medication, therapy, or a combination of the two to relieve their symptoms and regain their normal function. This study sought to determine if behavioural activation therapy (a psychological intervention) was as effective as antidepressant medication (fluoxetine) for adolescents diagnosed with depression.

Methods

This study randomly allocated adolescents between 12-16 years old, who met criteria for Major Depressive Disorder, to receive behavioural activation therapy or fluoxetine (Fluoxetin-Mepha®) over the course of 18 weeks. Those randomized to fluoxetine visited their psychiatrist regularly but did not receive psychotherapy. Those who received behavioural activation therapy received between 18-20 one-hour sessions of individual therapy that focused on increasing enjoying and rewarding behaviours. The primary outcome was the difference in mean change of depressive symptoms as measured with the Children's Depression Rating Scale - Revised (CDRS-R).

Because

The effects of behavioural therapy and fluoxetine (Fluoxetin-Mepha®) were investigated in this randomized-controlled trial, which included adolescents between 12-16 years old, who suffered from major depressive disorder. There is no treatment guideline that recommends prescribing antidepressants to this population without also prescribing psychotherapy.

Product according to Art. 2a para. 2 TPA

Can the product according to Art. 2a para. 2 TPA legally be placed on the Swiss market?
Explanation

Product according to Art. 2a para. 2 TPA

Is the use of the product according to Art. 2a para. 2 TPA prohibited in Switzerland ?
Explanation
The Swiss Agency for Therapeutic Products (Swissmedic) can prohibit the use of medically used products in Switzerland.
Is the product according to Art. 2a para. 2 TPA used according to the instructions for use?
Explanation
A medically used product is usually associated with a specification, or instructions for use, which describe the correct use of the Product.

Medical device: CE mark

Does the medical device bear a conformity mark?
Explanation
Conformity mark refers to the CE mark.
Case studies (2)
Answer

Yes

Title of study

Percutaneous coronary revascularization: a randomized comparison of a sirolimus-eluting stent with biodegradable polymer and an everolimus-eluting stent with a durable polymer

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Background

Drug-eluting coronary artery stents that release therapeutic agents locally, in a controlled fashion, have improved the safety and efficacy of percutaneous coronary interventions. This study compares the safety and efficacy of a sirolimus-eluting stent with a biodegradable polymer with that of an everolimus-eluting stent with a durable polymer. This is a prospective multicentre randomized controlled non-inferiority trial in patients who underwent percutaneous coronary intervention during routine clinical practice.

Methods

Subjects aged ≥18 years, who have a symptomatic coronary artery disease (including chronic stable angina, silent ischemia, and acute coronary syndromes including NSTE-ACS and STE-ACS), are randomized for treatment either with the CE-marked Orsiro® stent system (sirolimus-eluting stent with a biodegradable polymer) or a CE-marked Xience PRIME® stent system (everolimus-eluting stent with a durable polymer). Primary endpoints are target lesion failure (defined as the composite of cardiac death, as well as target vessel myocardial infarction, and clinically driven target-lesion revascularization). No off-label use and no additional invasive or burdensome procedures in addition to those performed under the normal conditions of use of the two devices are described in the study protocol.

Because

The effects of the Orsiro® stent system and the Xience PRIME® stent system were investigated in this trial. Both passed the required conformity assessment procedure, and so both stent systems bear a CE mark (conformity mark).

PDF summary
Answer

Yes

Title of study

A single arm, multi-centre clinical trial to evaluate the HeartWare® ventricular assist system (VAS) for destination therapy of advanced heart failure

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Background

Routine treatment with left ventricular assist devices (LVADs) bridges transplantation for patients with advanced heart failure. We aim to determine the safety and effectiveness of the HeartWare® Ventricular Assist System in patients with chronic advanced stage left ventricular ineligible for cardiac transplantation. The HeartWare® Ventricular Assist System is marketed in several countries, but the use of the System in Switzerland has been prohibited by Swissmedic.

Methods

We include patients with advanced heart failure symptoms (Stage D/NYHA Class IIIB or IV, ≥18 years old) who have received and failed optimal medical therapy, and are ineligible for cardiac transplantation. All patients receive the HeartWare® Ventricular Assist System. The primary endpoint of the trial is survival and freedom of re-interventions until cardiac transplantation.

Because

This trial investigated the effects of the HeartWare® Ventricular Assist System ("medical device"). The device passed the required conformity assessment procedure and bears a CE mark.

Medical device: administration

In Switzerland, is it forbidden to make the medical device available on the market, to put it into service or to use it on a person?
Explanation
The Swiss Agency for Therapeutic Products (Swissmedic) can prohibit medical devices with a CE mark in Switzerland.
Case studies (1)
Answer

Yes

Title of study

A single arm, multi-centre clinical trial to evaluate the HeartWare® ventricular assist system (VAS) for destination therapy of advanced heart failure

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Background

Routine treatment with left ventricular assist devices (LVADs) bridges transplantation for patients with advanced heart failure. We aim to determine the safety and effectiveness of the HeartWare® Ventricular Assist System in patients with chronic advanced stage left ventricular ineligible for cardiac transplantation. The HeartWare® Ventricular Assist System is marketed in several countries, but the use of the System in Switzerland has been prohibited by Swissmedic.

Methods

We include patients with advanced heart failure symptoms (Stage D/NYHA Class IIIB or IV, ≥18 years old) who have received and failed optimal medical therapy, and are ineligible for cardiac transplantation. All patients receive the HeartWare® Ventricular Assist System. The primary endpoint of the trial is survival and freedom of re-interventions until cardiac transplantation.

Because

This trial investigated the effects of the HeartWare® Ventricular Assist System ("medical device"). The device passed the required conformity assessment procedure and bears a CE mark. However, use of the HeartWare® Ventricular Assist System was prohibited in Switzerland during conduct of the trial.

Is the device used in accordance with its instructions for use (same indications, contraindications, parameters or settings, precautions)?
Explanation
A conformity mark (CE mark) for a medical device is usually associated with a specification, or instructions for use, which describe the correct use of the medical device.

Medical device: additional procedure

Are any additional invasive or burdensome procedures performed in the trial compared to standard care?
Explanation
When conducting a clinical trial, additional invasive procedures or procedures that are burdensome to the subject may be used specifically for the trial, which would not otherwise be undertaken in standard care. Additional procedures which are burdensome can include a wide variety of different interventions, this may include procedures which may cause pain, discomfort, fear, potential risks or complications/side-effects, disturbances of lives and personal activities, or otherwise unpleasant experiences. Additional procedures which are invasive include (but are not limited to) penetration inside the body through the surface of the body, including through mucous membranes of body orifices, or penetration of a body cavity via a body orifice.

Medical device: purpose of trial

Is the trial being conducted to use it to verify the performance, benefit, and/or safety of a product as part of the clinical evaluation of conformity?
Explanation
According to art. 62 para. 1 EU-MDR: This refers to clinical trials carried out as part of the clinical evaluation for conformity assessment purposes, for one or more of the following purposes: (a) to establish and verify that, under normal conditions of use, a device is designed, manufactured and packaged in such a way that it achieves the performance intended; (b) to establish and verify the clinical benefits of a device as specified; (c) to establish and verify the clinical safety of the device and to determine any undesirable side-effects, under normal conditions of use of the device, and assess whether they constitute acceptable risks when weighed against the benefits to be achieved by the device.
Is the trial being conducted to use it to verify the performance, benefit, and/or safety of a product as part of the clinical evaluation of conformity?
Explanation
According to art. 62 para. 1 EU-MDR: This refers to clinical trials carried out as part of the clinical evaluation for conformity assessment purposes, for one or more of the following purposes: (a) to establish and verify that, under normal conditions of use, a device is designed, manufactured and packaged in such a way that it achieves the performance intended; (b) to establish and verify the clinical benefits of a device as specified; (c) to establish and verify the clinical safety of the device and to determine any undesirable side-effects, under normal conditions of use of the device, and assess whether they constitute acceptable risks when weighed against the benefits to be achieved by the device.

Intervention not involving therapeutic products: risks for participants

Does the intervention involve minimal risks and stress for the participating persons?
Explanation
Interventions in connection with clinical trials which are not considered to be therapeutic products as defined in the Therapeutic Products Act, transplant products or a transplantation, may be associated with minimal or more than minimal risks and burdens for the participating persons. Interventions with minimal risks and burdens include those which, in all likelihood, are associated with no, or at most mild and transient, physical or psychological effects (including unpleasant social consequences, e.g. a stigmatising effect) for the participating person. The risks and burdens should be assessed as objectively as possible, taking account of the specific condition and degree of vulnerability of the participating person, and on the basis of the latest scientific findings.Interventions in connection with clinical trials which are not considered to be therapeutic products as defined in the Therapeutic Products Act, transplant products or a transplantation, may be associated with minimal or more than minimal risks and burdens for the participating persons. Interventions with minimal risks and burdens include those which, in all likelihood, are associated with no, or at most mild and transient, physical or psychological effects (including unpleasant social consequences, e.g. a stigmatising effect) for the participating person. The risks and burdens should be assessed as objectively as possible, taking account of the specific condition and degree of vulnerability of the participating person, and on the basis of the latest scientific findings.
Case studies (4)
Answer

Yes

Title of study

Optimal duration of dual antiplatelet therapy after coronary stent implantation

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Background

Patients receiving a coronary stent during a percutaneous corornary intervention need to take dual antiplatelet therapy after the procedure. The aim of the antiplatelet therapy is to prevent patients from stent-related blood clots and other major adverse cardiovascular events following the implantation. Dual antiplatelet therapy consists of regular intake of oral aspirin and a second anti clotting drug. The aim of the study was to evaulate the optimal duration of such a dual antiplatelet therapy.

Methods

Patients undergoing stent placement for the treatment of coronary artery lesions were randomized to receive a prescription for clopidogrel for 12 months or 24 months. In addition, all patients received a prescription for aspirin life-long. Patients were responsible to obtain the prescribed treatment with the prescription at their local pharmacy. Randomized prescriptions specified the International Nonproprietary Name (INN) and therefore left the descision on which specific preparation (proprietary medicinal product) to be handed to the patient at the discretion of the pharmacist. Patients were assessed every 6 months. Patients in the 12-month arm were reminded to stop treatment of clopidogrel at the 12-month visit and patients in the 24-month arm at the 24-month visit. Patients were followed-up for 5 years. The trial had two primary outcomes: 1) the composite of all-cause death and major cardiovasular events at 24-month follow-up; 2) major bleeding events at 24-month follow-up.

Because

This randomized-controlled, open trial investigates the effects of different lengths of clopidogrel treatment. Clopidogrel is a drug and various proprietary medicinal products are "authorised" for the Swiss market (e.g. approval number for Plavix®: 54509 (Swissmedic)). It is reasonable to assume that pharmacies will only provide authorised products to the patients. All authorised clopidogrel preparations are approved for prevention of atherothrombotic events in patients who received a coronary stent. The recommended dosing schedule is corresponds to dosing schedule in the protocol. Length of treatment is not explicitly mentioned in the package insert but only mentioned as long-term.Therefore, indication and dosage of clopidogrel in this research project corresponds with the approved indication.

Answer

Yes

Title of study

Effect of and intervention designed to increase physical activity, reduce sedentary behaviour, and increase children’s consumption of fruit and vegetables: Active for Life School Year-based cluster randomised controlled trial.

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Background

This study investigated the effectiveness of a school-based intervention to increase physical activity, reduce sedentary behaviour, and increase children’s consumption of fruit and vegetables.

Methods

Participants were children in school year 4 (age 8-9 years) at recruitment and baseline assessment, and in year 5 during the intervention and follow-up assessments. Schools were randomly allocated to receive either the Active for Life intervention or standard teaching. The Active for Life intervention provided teacher training, lessons, and child-parent interactive homework plans, the materials required for lessons and homework, and written materials for school newsletters and parents. Schools in the control group received standard teaching. Pre-specified primary outcomes were accelerometer assessed minutes of moderate to vigorous physical activity per day, accelerometer assessed minutes of sedentary behaviour per day, and reported daily consumption of servings of fruit and vegetables.

Because

The study asked if the Active for Life intervention increased physical activity, reduced sedentary behaviour, and increased children’s fruit and vegetable more than standard teaching did. Teaching interventions do not create more than minimal risk or stress to participants.

Answer

Yes

Title of study

Balance in young female ballet students suffering from chronic knee pain: The effect of physiotherapy with and without a mirror.

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Background

In literature there is general consensus that using a mirror improves proprioception. During rehabilitation, a mirror is very useful for improving stability. In some sports, such as dancing, mirrors are widely used in training. This study evaluated the effectiveness of physiotherapy with mirror on balance in young dancers.

Methods

This study included young dancers (aged 19-25) suffering from chronic knee pain. They were randomly assigned to receive physiotherapy, one to one, with a mirror (mirror- group) or without a mirror (non-mirror group). Their balance was evaluated by BESS (Balance Error Scoring System), which consists of three stances (double limb, single limb, and tandem) on two surfaces (firm and foam). Errors were assessed at each stance and summed to create the two subtotal scores (firm and foam surface) and the final total score (BESS). The BESS was measured at recruitment (T0) and again after 6 months of dance lessons (T1). Primary outcome was difference in total BESS between the groups.

Because

The investigator randomly assigned ("prospectively assigned") female dancers suffering from chronic knee pain to receive physiotherapy either with or without a mirror. The study assessed between-groups difference via the Balance Error Scoring System ("to investigate structure and function on the human body"). Dancing in front of a mirror creates minimal risk or stress in participants.

Intervention not involving therapeutic products: medical standard

Does administration comply with standard medical practice as defined in guidelines developed in accordance with international quality critieria?
Explanation
An appliation of the intervention to be investigated corresponds to a medical standard if it is presented as standard in a guideline drafted in accordance with internationally recognised quality criteria. Standardised uses of medical measures are described in medical (therapeutic) guidelines (clinical practice guidelines) in respect of benefit, safety and effectiveness. If the intervention to be investigated in the clinical trial meets the requirements stated in a broadly supported, evidence-based guideline, it can be assumed that the risk of the intervention to be investigated is comparable with the risk of the standard treatment that is normally employed in medical practice. In recent decades, established quality standards have emerged which are intended to form the basis for the drafting of medical guidelines in order for these to be recognised internationally in medical practice. The recommendations on the development of medical guidelines issued by the Council of Europe in 2002 constituted a major contribution to the further development of quality criteria for medical guidelines. They led to the drafting, by an internal collaboration in 2009, of an instrument known as AGREE II (Appraisal of Guidelines for Research and Evaluation) for the development of guidelines and the evaluation of the methodological stringency and transparency with which a guideline was developed. This instrument is now used by many international organisations and is recommended by WHO for the development and evaluation of guidelines. Numerous guidelines in various disciplines have been investigated for their quality and described in the scientific literature with the aid of this tool. Recently, at the request of the US Congress, the American Institute of Medicine (IOM) of the National Academies refined the standards for medical guidelines on the basis of AGREE II, and specifically addressed certain aspects, for example the management of conflicts of interest, the funding of the preparation of the guideline and the requirement for systematic reviewing of existing evidence. An appliation of the intervention to be investigated corresponds to a medical standard if it is presented as standard in a guideline drafted in accordance with internationally recognised quality criteria. Standardised uses of medical measures are described in medical (therapeutic) guidelines (clinical practice guidelines) in respect of benefit, safety and effectiveness. If the intervention to be investigated in the clinical trial meets the requirements stated in a broadly supported, evidence-based guideline, it can be assumed that the risk of the intervention to be investigated is comparable with the risk of the standard treatment that is normally employed in medical practice. In recent decades, established quality standards have emerged which are intended to form the basis for the drafting of medical guidelines in order for these to be recognised internationally in medical practice. The recommendations on the development of medical guidelines issued by the Council of Europe in 2002 constituted a major contribution to the further development of quality criteria for medical guidelines. They led to the drafting, by an internal collaboration in 2009, of an instrument known as AGREE II (Appraisal of Guidelines for Research and Evaluation) for the development of guidelines and the evaluation of the methodological stringency and transparency with which a guideline was developed. This instrument is now used by many international organisations and is recommended by WHO for the development and evaluation of guidelines. Numerous guidelines in various disciplines have been investigated for their quality and described in the scientific literature with the aid of this tool. Recently, at the request of the US Congress, the American Institute of Medicine (IOM) of the National Academies refined the standards for medical guidelines on the basis of AGREE II, and specifically addressed certain aspects, for example the management of conflicts of interest, the funding of the preparation of the guideline and the requirement for systematic reviewing of existing evidence.

Transplant product: status of market authorization

Is the transplant product authorised in Switzerland?
Explanation
A transplant product is considered to be authorised if it has been authorised by the Swiss Agency for Therapeutic Products (Swissmedic) for placing on the market in Switzerland (distribution and dispensing). Authorised transplant products can be viewed on the Swissmedic website (http://www.swissmedicinfo.ch/).

Transplant product: administration

Does administration of the transplant product in the study comply with the specifications in the summary of product characteristics (SPC)?
Explanation
The transplant product to be investigated will be used in accordance with the provisions of the Information for healthcare professionals approved by Swissmedic, if the application specifications in the Information for healthcare professionals are observed in respect of the indications, dosage, pharmaceutical form and patient group.
Does deviation from the specifications in the SPC concern the indication or dosage?
Explanation
The use of the transplant product to be investigated deviates from the specifications stated in the Information for healthcare professionals only in respect of the indications or specified dosages. If, during the use of the transplant product, the pharmaceutical form differs from that specified in the Information for healthcare professionals, the question must be answered with No.

Transplant product: indication

Does the indication lie within the same disease group in the ICD-10 classification as stated in the SPC (disease group indicated by three-digit code)?
Explanation
The use of the transplant product to be investigated deviates minimally, at most, from the indications cited in the Information for healthcare professionals, if the disease to be treated in connection with the clinical trial belongs to the same indication group to which the indications cited in the Information for healthcare professionals are also assigned. The indication group is defined by the three-character code of the single axis and mono-hierarchical classification system known as the "International Statistical Classification of Diseases and related Health Problems" ICD-10 (http://apps.who.int/classifications/icd10/browse/2010/en), for the indication forming the focus of the clinical trial. The risks and burdens for the participants associated with the use of the transplant product for an indication that can be assigned to the same indication group as at least one indication specified in the Information for healthcare professionals, remain comparable with those associated with the use for an authorised indication. This should be substantiated in terms of its proximity to the standard treatment / authorised use of the transplant product.

Transplant product: dosage

Is the disease for which the transplant product in the clinical trial is administered a self-limiting disease?
Explanation
A disease is described as self-limiting if the sufferer recovers spontaneously or without therapeutic measures.
Is the dosage is lower than specified in the SPC?
Explanation
-

Transplant product: medical standard

Does the administration of the transplant product comply with standard medical practice as defined in a treatment guideline developed in accordance with international quality critieria?
Explanation
A use of the transplant product to be investigated corresponds to a medical standard if it is presented as standard in a guideline drafted in accordance with internationally recognised quality criteria. Standardised uses of transplant products are described in medical (therapeutic) guidelines (clinical practice guidelines) in respect of benefit, safety and effectiveness. If the use of the transplant product in the clinical trial meets the requirements stated in a broadly supported, evidence-based guideline, it can be assumed that the risk of the intervention to be investigated is comparable with the risk of the standard treatment that is normally employed in medical practice. In recent decades, established quality standards have emerged which are intended to form the basis for the drafting of medical guidelines in order for these to be recognised internationally in medical practice. The recommendations on the development of medical guidelines issued by the Council of Europe in 2002 constituted a major contribution to the further development of quality criteria for medical guidelines. They led to the drafting, by an internal collaboration in 2009, of an instrument known as AGREE II (Appraisal of Guidelines for Research and Evaluation) for the development of guidelines and the evaluation of the methodological stringency and transparency with which a guideline was developed. This instrument is now used by many international organisations and is recommended by WHO for the development and evaluation of guidelines. Numerous guidelines in various disciplines have been investigated for their quality and described in the scientific literature with the aid of this tool. Recently, at the request of the US Congress, the American Institute of Medicine (IOM) of the National Academies refined the standards for medical guidelines on the basis of AGREE II, and specifically addressed certain aspects, for example the management of conflicts of interest, the funding of the preparation of the guideline and the requirement for systematic reviewing of existing evidence.

Gene therapy/pathogenic organism: status of market authorization

Is the gene therapy or pathogenic organism authorised in Switzerland?
Explanation
The gene therapy or pathogenic organism is considered to be authorised if it has been authorised by the Swiss Agency for Therapeutic Products (Swissmedic) for placing on the market in Switzerland (distribution and dispensing). Authorised gene therapies or pathogenic organisms can be viewed on the Swissmedic website (http://www.swissmedicinfo.ch/).

Gene therapy/pathogenic organism: administration

Does the administration of gene therapy or pathogenic organisms comply with the specifications in the summary of product characteristics (SPC)?
Explanation
The gene therapy or pathogenic organism to be investigated will be used in connection with the clinical trial in accordance with the provisions of the Information for healthcare professionals approved by Swissmedic, if the application specifications in the Information for healthcare professionals are observed in respect of the indications, dosage, pharmaceutical form and patient group.
Does the deviation from the specifications in the SPC concern the indication or dosage?
Explanation
The application of the gene therapy or pathogenic organism to be investigated deviates from the specifications stated in the Information for healthcare professionals only in respect of the indications or specified dosages. If, during the use of the gene therapy or pathogenic organism, the pharmaceutical form differs from that specified in the Information for healthcare professionals, the question must be answered with No.

Gene therapy/pathogenic organism: indication

Does the indication lie within the same disease group in the ICD-10 classification as stated in the SPC (disease group indicated by three-digit code)?
Explanation
The appliation of the gene therapy or pathogenic organism to be investigated deviates minimally, at most, from the indications cited in the Information for healthcare professionals, if the disease to be treated in connection with the clinical trial belongs to the same indication group to which the indications cited in the Information for healthcare professionals are also assigned. The indication group is defined by the three-character code of the single axis and mono-hierarchical classification system known as the "International Statistical Classification of Diseases and related Health Problems" ICD-10 (http://apps.who.int/classifications/icd10/browse/2010/en). The risks and burdens for the participants associated with the use of the gene therapy or pathogenic organism for an indication that can be assigned to the same indication group as at least one indication specified in the Information for healthcare professionals, remain comparable with those associated with the use for an authorised indication. This should be substantiated in terms of its proximity to the standard treatment / authorised use of the gene therapy or pathogenic organism.

Gene therapy/pathogenic organism: dosage

Is the disease for which the gene therapy or pathogenic organism is administered in the clinical trial a self-limiting disease?
Explanation
A disease is described as self-limiting if the sufferer recovers spontaneously or without therapeutic measures.
Is the dosage is lower than specified in the SPC?
Explanation
-

Gene therapy/pathogenic organism: medical standard

Does the administration of gene therapy or pathogenic organisms comply with standard medical practice as defined in a treatment guideline developed in accordance with international quality critieria?
Explanation
A application of the gene therapy or pathogenic organism to be investigated corresponds to a medical standard if it is presented as standard in a guideline drafted in accordance with internationally recognised quality criteria. Standardised uses of gene therapies or pathogenic organisms are described in medical (therapeutic) guidelines (clinical practice guidelines) in respect of benefit, safety and effectiveness. If the gene therapy or pathogenic organism to be investigated in the clinical trial meets the requirements stated in a broadly supported, evidence-based guideline, it can be assumed that the risk of the intervention to be investigated is comparable with the risk of the standard treatment that is normally employed in medical practice. In recent decades, established quality standards have emerged which are intended to form the basis for the drafting of medical guidelines in order for these to be recognised internationally in medical practice. The recommendations on the development of medical guidelines issued by the Council of Europe in 2002 constituted a major contribution to the further development of quality criteria for medical guidelines. They led to the drafting, by an internal collaboration in 2009, of an instrument known as AGREE II (Appraisal of Guidelines for Research and Evaluation) for the development of guidelines and the evaluation of the methodological stringency and transparency with which a guideline was developed. This instrument is now used by many international organisations and is recommended by WHO for the development and evaluation of guidelines. Numerous guidelines in various disciplines have been investigated for their quality and described in the scientific literature with the aid of this tool. Recently, at the request of the US Congress, the American Institute of Medicine (IOM) of the National Academies refined the standards for medical guidelines on the basis of AGREE II, and specifically addressed certain aspects, for example the management of conflicts of interest, the funding of the preparation of the guideline and the requirement for systematic reviewing of existing evidence.