Inappropriate and counterproductive safety reporting

Conservative definitions of Suspected Unexpected Serious Adverse Reactions (SUARs) and disproportionate reporting requirements—in particular, by contract research organisations (CROs)—have led to an overwhelming volume of safety reports, which prevents clinical researchers from identifying the truly important safety signals amid an unmanageable number of trivial queries and unfiltered notifications, thus posing a threat to patient safety.

Inadequate informed consent and reconsent

Currently, these documents are often lengthy, written in legal language and, therefore, difficult to understand. Instead, informed consent forms and reconsent procedures should be clear, accurate and limited to what is relevant for the patient. Ethics committees should see to it that consent forms serve their primary purpose—to inform the patient—and patients themselves should be involved in their design.

Overinterpretation of regulations and guidelines

There is a pressing need to review and rewrite guidance documents, in particular the International Council for Harmonisation (ICH) E6: Good Clinical Practice (GCP), to address textual ambiguity. Imprecise and vague texts leave the door open to overinterpretation of regulations, leading for instance to excessive on-site monitoring and increasing the cost of clinical trials disproportionately. There is widespread concern that potential overinterpretation of General Data Protection Regulation (GDPR) requirements will add to the administrative burden on researchers. Ultimately, GCP guidelines need to be clear, concise, consistent and proportionate.4

To address these issues, a more flexible and adaptable regulatory environment is needed. It is unquestionable that safety and quality of clinical trials are paramount, yet this should not be used as an excuse to delay much-needed simplification measures.

A clear indication that quick and pragmatic adaptation of guidance is possible, without compromising either safety or quality, is the Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic issued by European regulators on 31 March 2020.5 The measures to make consent, (remote) monitoring and auditing easier and to facilitate the submission of large multinational trial protocols—although their impact may be offset in part by requirements to register each and every modification—have been widely welcomed by investigators and patients.

More structural and comprehensive measures are needed to overcome the disruption and deceleration of clinical research in Europe due to the accumulation of administrative demands that were visible long before the arrival of COVID-19.6 We, therefore, welcome the plans for a thorough revision of the ICH E6(R3) guidelines on Good Clinical Practice. The involvement of patients and healthcare professionals from an early stage is promising, as are the signals that issues around safety reporting, informed consent, textual ambiguity and complexity will be addressed.

The new EU Clinical Trials Regulation No 536/2014 (EU CTR) is in operation since 31 January 2022. According to its own proclamation, the EU CTR is intended to harmonise the evaluation and monitoring processes for clinical trials throughout the EU via a Clinical Trials Information System. So far, the implications are in favour of sponsors and not so much of researchers, but time is needed to see developments.

Europe’s medical societies (many of them collaborating within the BioMed Alliance) and patient organisations stand ready and willing to assist the ICH and make this revision of GCP guidelines work.

Pushing back bureaucracy can only be done effectively if the rewriting of guidance is done in a way that reflects the broader need for advancing patient-centred, agile, risk-based clinical trials. Procedures and methods used to ensure GCP compliance should be proportionate to the risks and characteristics of a specific trial/treatment. Targeted guideline revisions need to contribute to a regulatory environment that puts the patient at the centre of clinical research. Reducing bureaucracy and improving patient safety, trial quality, access and affordability go hand in hand.

This statement by the BioMed Alliance is larger than this letter and has specific proposals, especially in relation to safety reporting (https://bureaucracyincts.eu/).

This is a collective and urgent appeal by medical associations and patient advocates across disciplines to all involved—in particular, policymakers and regulators at EU and national levels, ethics committees and the pharmaceutical industry—to agree on risk-based pragmatic simplification measures to address the issues mentioned above. The shared goal must be a substantial reduction of bureaucratic obstacles in clinical trials, not (only) as a response to current exceptional circumstances but also on a permanent basis. What is at stake is the efficiency and affordability of clinical trials, and with it the quality of future healthcare and, ultimately and most importantly, patient safety.