Generating comparative evidence on new drugs and devices before approval

Abstract

Fewer than half of new drugs have data on their comparative benefits and harms against existing treatment options at the time of regulatory approval in Europe and the US. Even when activecomparator trials exist, they may not produce meaningful data to inform decisions in clinical practice and health policy. Recently, the uncertainty associated with the paucity of well-designed active-comparator trials has been compounded by legal and regulatory changes in Europe and the US that have created a complex mix of expedited programs aimed at facilitating faster access to new drugs. Comparative evidence generation is even sparser for medical devices. Some have argued that the current process for regulatory approval needs to generate more evidence that is useful for patients, clinicians, and payers in health care systems. We propose a set of 5 key principles relevant to the European Medicines Agency (EMA), European medical device regulatory agencies, and the US Food and Drug Administration (FDA), as well as payers, that we believe will provide the necessary incentives for pharmaceutical and device companies to generate comparative data on drugs and devices and assure timely availability of evidence that is useful for decision making. First, labeling should routinely inform patients and clinicians whether comparative data exist on new products. Second, regulators should be more selective in their use of programs that facilitate drug and device approvals on the basis of incomplete benefit and harm data. Third, regulators should encourage the conduct of randomised trials with active comparators. Fourth, regulators should use prospectively-designed network meta-analyses based on existing and future randomised trials. Fifth, payers should use their policy levers and negotiating power to incentivise the generation of comparative evidence on new and existing drugs and devices, for example, by explicitly considering proven added benefit in pricing and payment decisions.

Clinical translation and implementation of optical imaging agents for precision image-guided cancer surgery

“…Ex vivo or in vitro comparison of clinical imaging systems with a tumorspecific imaging agent, especially laparoscopic systems, rarely leads to adequate and comparable data. Moreover, due to different legislations, the speed of development of imaging systems significantly exceeds that of imaging agents [28]. As a consequence, soft-and hardware might change during the transition from preclinical to phase II-III studies and can significantly influence the image acquisition [29].…”

Cluster randomised trials of prescribing policy: an ethical approach to generating drug safety evidence? A discussion of the ethical application of a new research method

“…For any medical condition, there may be several licensed treatment options with similar modes of action. Additionally, the evidence used to support licensing applications is usually from randomised controlled trials of limited duration and using non-representative care pathways [2]. External validity is further limited by trial participation being restricted to exclude individuals with comorbidities.…”

Producing and using timely comparative evidence on drugs: lessons from clinical trials for covid-19

“…Indeed, the multiplicity of research on candidate therapeutics for covid-19 has exposed important flaws and failures in the current evidence ecosystem 67. Crucially, these limitations also affect the full spectrum of research on new health technologies 89…”

“…Users of evidence across the healthcare system (patients, clinicians, health technology assessment bodies, guideline developers, payers) need timely data on how different treatments compare with each other in terms of their benefits and harms—their comparative effectiveness. Producing comparative evidence and ensuring its rapid translation into trustworthy guidance requires extensive coordination and collaboration between the researchers conducting clinical trials, those conducting comparative effectiveness assessments, and those producing guidance 89. The experience of covid-19 highlights the difficulties in making comparative assessments and suggests areas for improvement.…”