Between 5% and 16% of clinical trials conducted in the US fall into a regulatory gap between existing provisions for drugs and medical devices, a new study indicates.

A research team led by Dr Deborah Zarin, director of the registry at the National Institutes of Health, analysed nearly 24,000 active human-research trials based in the US, to determine where they fitted in the regulatory framework established by the country’s primary federal human-subject protection (HSP) policies.

These policies, which include requirements for institutional review-board review and informed consent, are enshrined in the US Food and Drug Administration (FDA) HSP regulations and the Common Rule.  

The HSP regulations cover FDA-regulated clinical investigations of drugs, biologics, and devices, regardless of the funding source. The Common Rule applies to human studies funded or conducted by 17 federal entities, regardless of the type of intervention studied.

Overlap or gap

As Zarin et al point out, there are differences between these regulations, even though they are largely consistent.

Concerns have been raised about the burdens imposed on studies covered by both regulations (overlap trials), and about some studies covered by neither (gap trials).

The research team looked at records of active trials listing at least one US-based facility as of September 2013.

From these, they extracted the intervention type; regulatory status in terms of investigational new drug application or investigational device exemption; trial sponsor; and collaborators.

The researchers also approximated, using narrow and broad criteria, the number of trials subject to each of the aforementioned regulations.

Out of 23,936 sampled trials, the authors estimated that 55% to 65% were subject to FDA HSP regulations only; 6% to 10% were covered by the Common Rule only; 19% to 24% were overlap trials that studied drugs and devices and attracted some federal funding; and 5% to 16% were gap trials that studied interventions other than drugs or devices (e.g., behavioural, surgical) and had no federal funding.

Vulnerable populations

The characteristics of these gap trials varied widely, but they included research in vulnerable populations (e.g., pregnant women, people with major mental illnesses, children) with primary outcomes that reflected potentially consequential risks such as organ failure, depression relapse, seizure frequency or hospitalisation.

According to Zarin et al, their analysis provides the first quantitative estimate of the gap in regulatory coverage for US-based clinical trials, while documenting a large number of studies that are subject to both the Food and Drug Administration HSP regulations and the Common Rule. 

While the data generated “are not precise measures of the current scope of different regulatory categories”, they represent the best current estimates and are intended to inform “ongoing discussions about potential regulatory reforms”, the authors note.