Non-interventional studies

While phase I-IV clinical trials investigate the efficacy of a study product in a patient population according to a clinical trial protocol, non-interventional studies treat patients in daily clinical practice under real-life conditions.

Non-interventional studies are regulated differently depending on the classification of the product:

• § Section 4 (23) of the German Medicines Act (AMG)

"The non-interventional trial is a study in which findings from the treatment of persons with medicinal products are analyzed using epidemiological methods; the treatment, including diagnosis and monitoring, does not follow a predetermined trial protocol, but exclusively medical practice; in the case of a medicinal product subject to authorization or subject to approval in accordance with Section 21a (1), this is also carried out in accordance with the specifications for its use specified in the authorization or approval."

• § Section 15 of the Professional Code of Conduct (BO) for physicians practicing in Germany
• formerly § 23b MPG
• Art. 83 and Annex XIV, Art. 74 or 82 of the EU MDR 2017/745
• as "other clinical trial" according to § 3 para. 4 and the requirements according to § 47 of the Medical Device Law Implementation Act (MPDG), which is to be read in conjunction with the EU MDR 2017/745

Application observations

Post-marketing surveillance studies (PMA) are studies that are intended to gather information on the use of authorized or registered medicinal products. Post-marketing surveillance studies are non-interventional trials within the meaning of Section 4 (23) sentence 3 of the German Medicinal Products Act (AMG).

AWB are not subject to approval, but are notified. According to Section 67 (6) (10) AMG, the competent higher federal authority makes the notifications and final reports submitted to it available to the public on the Internet.

The Medical Devices Regulation (EU) 2017/745 (EU MDR 2017/745) also regulates post-market clinical follow-up (Article 74, post-market clinical follow-up; PMCF, Annex XIV) and post-market surveillance (PMS, Article 83) for clinical evaluation (Annex XIV, Article 61) via clinical trials (Annex XIV, Articles 62-82). The clinical evidence for PMCF and PMS can be obtained via observational studies in compliance with the regulations.

Post-authorization efficacy testing of a drug (PAES)

A post-authorization efficacy study (PAES) is conducted to improve the understanding of the therapeutic efficacy and benefit-risk of a medicinal product with implications for optimal use in clinical practice. The design of the study should be ethically and scientifically justified.

The European Medicines Agency (EMA) has developed scientific guidance describing how studies should be designed to support regulatory decision-making in the European Union.

Post-approval safety test (PASS)

A post-authorization safety study pursuant to Section 4 (34) AMG is defined as follows: "A safety study of a medicinal product intended for human use is any study of an authorized medicinal product conducted to identify, characterize or quantify a safety risk, to confirm the safety profile of a medicinal product or to measure the efficacy of risk management measures."

A post-approval safety test can be ordered or voluntarily initiated, financed and carried out by the contractor.

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