The impact of FDA’s new focus on ensuring clinical trials include broader populations may be unknown at the moment, but CDER’s Robert Temple does not think it will create havoc for sponsors.

FDA late last year issued a new Manual of Policies and Procedures (MaPP) document emphasizing that broad clinical trial populations should become a regular part of agency evaluations of trials and development plans. The agency wants to stop trial exclusions that would be deemed unnecessary.

The overall intent is to make more information available for clinicians about the use of the drugs FDA approves.

Patients with psychiatric and other conditions have been identified as groups that should be included in trials because it is important to learn how new drugs affect those populations Also see "Patient Exclusion Analysis Coming From FDA; Changes In Trial Recruitment Could Follow" - Pink Sheet, 10 July, 2012..

FDA also is making a concerted effort to make sure patients older than 75 are not unnecessarily excluded.

Temple, Center for Drug Evaluation and Research deputy director for clinical science, said during a Jan. 31 press event that that it is too early to tell if the push against unneeded exclusions has affected new trial proposals.

But he also said the new policy should not make trials or statistical analyses tougher.

“I think for symptomatic conditions there probably is not a major reason to worry about effectiveness,” Temple said. “What you’re hoping is that if there’s some demographically-related side effect, you’ll pick it up, but that shouldn’t affect the ability of the study to show something.”

A recent Institute of Medicine report argued that efforts should be undertaken to make large trials simpler, including using broad eligibility criteria to gain a diverse patient population and make the data more generalizable Also see "Large Simple Trials Need FDA Boost, IoM Report Says" - Pink Sheet, 14 October, 2013..

Staff Will Question Need For Exclusion

The new MaPP adds checklists to be included in the review of an End-of-Phase II package or trial protocol and advises reviewers to discourage exclusions that are unnecessary and encourage sponsors to use broad inclusion criteria.

Detailed considerations also are expected of trial populations as well as special populations and demographic subgroups, including subgroup analyses, elderly subjects and other subpopulations.

In a Dec. 2, 2013, internal FDA memo on the new policy, Temple said reviewers should make “consideration of why exclusions are needed or appropriate” a part of their standard operating procedures.

“The goal is for us to become more cognizant of exclusion criteria, to examine such criteria closely, and to encourage removal of exclusions that are unnecessary,” he wrote in the memo. “Unnecessary exclusions can create doubts about the applicability of study findings to excluded populations.”

Temple has called them “stupid exclusions” and said FDA will be more closely watching for them Also see "FDA To Be More Vigilant About Proposed Clinical Trial Exclusions" - Pink Sheet, 16 September, 2013..

The clinical trial inclusion policy is part of FDA’s role in a Department of Health and Human Services strategy to improve the health of patients with multiple chronic conditions, released in December 2010.

No Enrichment Issues Expected

Temple said many large outcome trials look at a broad array of subsets and tend to be mostly inclusive. But he said applying an inclusion policy to other clinical trials could have affected decision-making in the past.

He said information like how platelet inhibitors affect patients older than 75 may not affect a drug candidate’s approvability, but still is something the agency would like to know.

“I don’t know what we’re going to find,” Temple said. “If you don’t try to look, you won’t find it out.”

Temple also said the inclusion policy shouldn’t affect enrichment trial designs, which are intended to make a drug’s effect more obvious by enrolling patients more likely to respond.

“We try to make very clear that the fact that we want a broad population doesn’t mean that an intelligent enrichment design is unacceptable and in most places those will not conflict,” he said. “This is not attempting to discourage enrichment. It just says within the population you’re looking at try not to have unnecessary exclusions.”

Draft guidance on enrichment designs also states that it is important for sponsors to collect data on the population less likely to respond in addition to the target group ([A#00130408002]).

In a 2013 report, FDA said trial population data could be more diverse, but that diversity alone should not be the sole focus ([A#00130826011]).

FDA’s Clinical Trial Inclusion Policy Sold As Mild And Gentle

More from United States

More from North America