A coalition of medical associations and patient advocates across disciplines is calling on European policymakers and regulators at the EU and national levels, ethics committees and the pharmaceutical industry to agree on measures to reduce bureaucracy in clinical trials.
The Coalition for Reducing Bureaucracy in Clinical Trials describes itself as "a key stakeholder in the implementation of the EU Clinical Trials Regulation and modernisation of clinical trials generally, as the voice of academic investigators and patient advocates in Europe."
TranspariMED is not a member of the Coalition and lacks the expertise required to take position on many of its recommendations. We reproduce the Coalition's recommendations verbatim below in the hope that this will stimulate a wider debate.
The impact of accumulating administrative burdens is best described by the trial investigators who face them on a daily basis and by the patients who struggle with the ‘consent bureaucracy’ and whose safety may not be optimally guaranteed when their clinicians struggle to manage excessive volumes of safety reports which threaten to drown out the real risks.
The investigator will receive notifications on safety issues from the clinical research organisations (CROs) on a daily basis. Reports listing all Suspected Unexpected Serious Adverse Reactions (SUSARs) and Serious Adverse Events (SAEs) need to be read and signed by the investigator, a requirement that becomes particularly burdensome if the investigator is part of multiple trials.
Dr Jeanette Doorduijn, hematologist:
“I would like to see some responsibility going to sponsor and CRO. Filter relative safety issues that need to be reported to investigators, the SUSARs, and only send a report on all reported SAEs every three months or so, with a special part for SAEs that have not been reported before.” This would ensure that the investigator knows what to look for and minimize the multiple pages of documentation received daily. In the current situation, as Dr Doorduijn points out, “The CROs or sponsors make no difference at all in SAEs and SUSARs. This [filtering relative safety issues] should be the task of their safety departments”.
‘Over-informed’ and inadequate consent
From the perspective of a patient who enters a clinical trial and places his trust in the principal investigator by signing off on the informed consent form, the burden of bureaucracy lies in the fact that these forms are too long and contain too many complex formulations.
Privacy and security terms resulting from legislation such as the General Data Protection Regulation (GDPR), or overly scientific terminology in descriptions of the molecule, drug, and safety risks, often seem designed as an insurance policy covering the legal liabilities of trial sponsors rather than to ensure that the patient understands what he or she has agreed to.
As a patient advocate Richard Mindham illustrates: “Consent forms tend to be long and repetitive, with an apparent bias towards legal aspects rather than having a focus on imparting information to the patient about their possible involvement in a trial. The goal must be to provide patients with the information they need to participate in a trial without burdening them with legal complexity.” Of course, patients need to be aware of the protections available to them in law, but this should not cloud the purpose of the trial nor patients’ engagement in it.” Mr. Mindham goes on to explain that “many patients will come to a trial following a conversation with an investigator. Whilst they wish to be kept safe when they participate in a trial, the primary purpose of the consent form should be to confirm their understanding of the trial and to have something to discuss with family members”. Even for patients with a high level of education they [the informed consent forms] can be difficult to understand and the willing patient needs to put in a lot of work to understanding them and this can be a discouragement to many”.
Over-interpretation of regulatory guidelines
The Coalition for Reducing Bureaucracy in Clinical Trials has collaborated with the Good Clinical Trials Collaborative (GCTC) since the latter was established in 2020.
As part of two-way consultations and feedback, the Coalition provided input for the guidance document developed by GCTC. The two collectives also aligned their participation in discussions with the European Medicines Agency (EMA) and The International Council for Harmonisation (ICH), influencing the revision of ICH E6 Good Clinical Practice guidelines which set the international ethical and scientific quality standards for designing, conducting, recording, and reporting trials that involve the participation of human subjects4. The Coalition’s impact has also extended to the guidance documents developed by the European Commission (EC) and National Competent Authorities on implementation of the Clinical Trials Regulation (CTR). Although the CTR5 was adopted as far back as 2014, it only entered into application in January 2022, after EMA had delivered the Clinical Trials Information System (CTIS).
The Coalition advised the European Commission during its development of a Questions & Answers document on implementation of the CTR, which describes how to best conduct clinical trials and report safety issues but leaves open many questions around implementation.
This fruitful interaction has helped ensure that the updated guidance now has clear sections on how to report safety issues, which documents should be registered, and on interpretation of legal requirements that previously might have been too difficult to understand4. The investigators and sponsor can now draft the protocol in a way that prevents excessive reporting, a first step towards helping investigators such as Dr. Doorduijn and Dr. Marcela Fajardo-Moser, an investigator at University Hospital Würzburg, push back administrative burdens.
“Reducing bureaucracy in clinical trials goes hand in hand with a re-orientation on two prerequisites for cost-effective and conclusive clinical trials: the quality of study protocols and – this is key – never letting the patient out of focus. Better education of sponsors and investigators is needed on how to design streamlined study protocols that always focus on the well-being of the patients.”
In January 2022, the European Commission, the Heads of Medicines Agencies (HMA) and EMA launched an initiative to transform how clinical trials are initiated, designed, and run referred to as Accelerating Clinical Trials in the EU (ACT EU).
The strategy paper published by ACT EU listed ten priority actions for 2022-2023 including, notably, enabling innovative trial methods, establishing a multi-stakeholder platform, and supporting the modernisation of good clinical practice. The Coalition Recommendations in combination with the Coalition’s constructive engagement with regulators and guideline developers has already contributed to increased awareness on the need for harmonized and simplified safety reporting, less ambiguous regulatory guidelines, simplified informed consent forms and the urgency of decreasing bureaucracy in clinical trials.
In the process, the Coalition has positioned itself as a key stakeholder in the implementation of the CTR and modernisation of clinical trials generally, as the voice of academic investigators and patient advocates in Europe.
The Coalition welcomes enquiries and feedback on its suggestions.