Organization says either reform European drug development rules—or lose out on global competition.
One of the most influential organizations of professionals in the world of clinical trials has distilled the current European regulatory scene into a clear choice for the authorities: update pharmaceutical rules or abandon all hope of retaining global influence in medicines innovation. In its contribution to the current debate on the EU's ongoing review of its pharmaceutical legislation, the Association of Clinical Research Organizations (ACRO) pulls no punches.
It says, bluntly, that inconsistency of the EU makes approval and initiation of new clinical trials too slow. The consequence is that EU countries are often in the second or third rank when a clinical trial is initiated globally: so innovation in the EU is delayed, and patients suffer slower access to trials of novel treatments and ultimately delayed access to innovative products. ACRO highlights what it sees as areas of inefficiency and administrative burden, and warns starkly: "Research and development in the EU is losing ground to competitors such as China and the USA, and the EU is in danger of losing its leadership role in medical innovation."
ACRO's opinion can hardly be lightly dismissed: it represents the world's major clinical research and technology organizations, with more than 150,000 employees, including over 60,000 in Europe, and research activities in 114 countries. It has taken advantage of the EU invitation to indicate selected priorities in the rewrite of the pharma rules—which is due to appear as a firm proposal from EU officials before the end of 2022. And there is hardly a single aspect of the current rules that escapes a scathing assessment by ACRO, ranging from distinct national, local, and regional procedures for regulatory and ethical approval to a failure by regulators to keep up to date with the pace of science and technology.
The ACRO assessment is uncompromising. The EU must simplify its legislation and make its regulation attractive, by cutting regulatory approval times and costs, introducing flexibility and adaptability to innovative pathways in medicines development and evidence generation. A new framework must cater for genomics, for personalized medicine, for data analytics, and for digital tools, and must provide tailored incentives for innovation. Novel flexibilities such as the rolling reviews introduced for COVID-19 treatments "should become the standard process rather than an exception." And EU guidance should make provision for remote source data review.
Nor is ACRO reassured by the EU's extravagant claims that the new clinical trials regulation and information system herald a brave new world. This could be "an opportunity to improve efficiency and streamline overall regulatory processes," ACRO concedes cautiously. If it meets the rhetoric about “file once, use often” for marketing authorization evaluation without the need for resubmission of reports/data by applicants, it could help to reduce the overall timeline for evaluation of the marketing authorization application, ACRO hypothesizes. But only if it is "effectively implemented." And the ACRO submission does not express confidence that this will occur evenly enough to make a real difference. "It is too early to know to what extent the application of [the new CT regulation] will improve the situation and streamline regulatory and ethics committee approvals for pan-EU clinical trials," it observes. It is not optimistic: even with the new regulation, the assessment will take eight to 12 weeks from submission to approval of the application, it says, adding:"This compares with a typical period of four weeks in the USA."
Consequently, "until the EU has in place a process that provides a rigorous regulatory and ethical review with similar timelines, it will be difficult for the region to be competitive for clinical research, especially for early phase clinical trials," says ACRO. And persistent inflexibility around submission and processing of substantial modifications will likely lead to delays in implementation of changes required to clinical trials, further reducing the attractiveness of the EU, it adds.
On top of that, ACRO highlights limitations in the clinical trial information system now coming into force, notably in handling platform trials and other novel designs and in taking account of increased digitalization of clinical research and the trend toward submission of data rather than of reports. Meanwhile, it says, data protection implementation varies greatly across the member states, and diverse national approaches limit electronic informed consent and electronic signatures.
All this against a background of variability "caused by too many sites, and the inability of patients to participate because they do not fall within the small catchment area of a particular site." ACRO is calling for centralized patient records that would allow physicians and clinical investigators to offer patients not directly under their care the opportunity to participate in an appropriate clinical trial. But Europe is plagued by "unnecessary bureaucratic delays" that hamper patient access to trials. Among its most radical suggestions, the ACRO submission attacks the traditional distinction between clinical care and clinical research. "This outdated perspective fails to recognize the interconnectedness of clinical care and clinical research, thereby harming the competitiveness of the EU in clinical research," it says.
ACRO urges new rules that would oblige efforts at integration, such as "presenting clinical trials as a care option" and encouraging the “pre-consent” of individual patients about their willingness to be considered for clinical research projects. Branding this "a major omission," ACRO says the EU focus on ethical considerations and patient safety "does not reflect modern attitudes and approaches to patient centricity," it says, citing a chronic fragmentation of clinical care and clinical research. ACRO recommends adoption of “patient centricity by design,” with greater patient involvement and increased reliance on patient-reported outcomes in regulatory decision-making.
Overall, this is a damning assessment by professionals who spend their working lives grappling with the realities of designing and running clinical trials in what it sees as an obsolete EU framework. Among the 500 or so contributions the EU has received as it creates its new rules, ACRO's is conspicuous for its intense focus on clinical trials—although some of the points it makes are echoed in many of the submissions from the pharmaceutical industry. The outcome in terms of legislation will not, however, be conditioned uniquely by considerations of trial efficiency. The political context is, as ever, determinant in EU affairs, and that will respond not only to the aspirations of clinical trial professionals, but also to the views of patient and consumer groups that have repeatedly made clear their demands for tighter controls on all aspects of drug development, and their suspicion that calls for efficiency are merely a cloak for the headlong pursuit of deregulation.
Just how the EU proposes to resolve these tensions will become clearer over the coming months as the shape of its new legislative framework emerges.