CDER Snapshots Offer Clearer Picture Of Pivotal Trial Subgroup Data

Race-based enrollment disparities could put more pressure on industry to broaden trial recruitment, but FDA’s demographic data transparency initiative also could help companies differentiate their products.

An FDA pilot program to make clinical trial demographic data for approved drugs more transparent and easily accessible could end up costing the industry more in study recruitment expenses but could bring rewards once a drug reaches the market.

The Drug Trials Snapshot initiative aims to provide age-, race-, and gender-based information on clinical trial enrollment, efficacy and safety results for new molecular entities and novel biologics that clear the agency.

With an easy-to-use, “at a glance” format, the snapshots have the potential to shine new light on longstanding demographic disparities in drug development clinical research.

CDER plans to begin posting snapshots for all newly approved drugs and biologics in 2015.

This, in turn, could put further pressure on pharma companies, their contract research organizations and academic partners to undertake costly efforts to try to improve enrollment of such groups as minorities, women and elderly patients in future trials. Such efforts would add more money and time to the already lengthy and expensive process of enrolling and conducting such studies.

However, the snapshots’ delineation of efficacy and safety differences by demographic group also could serve as a marketing edge for sponsors looking to differentiate their products over the competition, particularly in crowded therapeutic areas like heart disease and diabetes.

Such information could prove particularly useful to sponsors if it ultimately makes its way into labeling. The agency is investigating how best to communicate such demographic subgroup data in product labels.

The Center for Drug Evaluation and Research is requesting comments on the format, content and overall usability of the snapshots to determine whether this approach is user friendly to the public. Comments are due by Jan. 23.

Starting in 2015, CDER intends to post snapshots for all NMEs and novel biologics “in close proximity” to their approval, the center said.

Dual Goals Of Transparency, Access

The snapshot program is part of FDA’s “Action Plan to Enhance the Collection and Availability of Demographic Subgroup Data,” which was required under the 2012 FDA Safety and Innovation Act.

Released in August, the plan outlines 27 short-, medium- and long-term steps to improve the completeness and quality of subgroup data collection, identify barriers to subgroup enrollment in clinical trials, and make demographic subgroup data more transparent (Also see "FDA Working To Make Subgroups Stand Out" - Pink Sheet, 21 Aug, 2014.).

The plan notes that although demographic composition and subgroup analyses are already included in medical product reviews posted on the agency’s website, they can be difficult to locate. It calls for CDER and the Center for Biologics Evaluation and Research to post demographic information from pivotal trials for newly approved drugs and biologics.

CDER is implementing this provision through its Drug Trials Snapshot website, which was rolled out Nov. 21. The center also posted an online interview with John Whyte, director of Professional Affairs and Stakeholder Engagement, discussing the initiative.

The pilot project includes snapshots for all five of the NMEs and novel biologics, covering six indications, approved by CDER in May and June 2014.

Each snapshot follows the same basic template, with a summary describing the drug’s indication, method of administration, benefits and side effects, and whether there were differences in how well the drug worked in clinical trials among sex, race and age.

A section entitled “Who Was In The Studies” contains various graphs and charts of baseline demographics in the efficacy and safety studies, including a breakdown by investigational treatment arm and placebo/comparator arm.

Efficacy results are presented as a whole and across various demographic characteristics, such as age, gender, race and region. In some snapshots, charts show treatment-emergent adverse events by demographic subgroup.

The detailed charts and tabular data, adapted from medical reviews, are in sharp contrast to the often sparse demographic subgroup information found in product labeling.

The snapshots include hyperlinks to product labeling and FDA medical reviews.

The charts and tabular data are adapted from the agency’s medical and statistical reviews for each drug application, which can run hundreds of pages long. As such, the level of detail presented in the snapshots stands in striking contrast to the often sparse demographic subgroup information found in product labeling.

“These snapshots allow consumers to actually see that people like them participated in clinical trials for a certain therapy,” Whyte said in the online interview. “One wasn’t able to easily access this data before. The snapshots are a game changer.”

Enrollment Disparities Readily Apparent

An analysis of the five snapshots reveals few instances in which there were efficacy or safety differences by demographic group.

However, disparities in enrollment are reflected by the inability to discern efficacy or safety differences in many of the cases due to limited clinical trial participation by minorities and older patients (see related chart, (Also see "Drug Trials Snapshots Debut With Five Novel Products" - Pink Sheet, 8 Dec, 2014.)).

Particularly notable are the enrollment disparities by race.

In the efficacy trial populations for the five drugs, the percentage of white subjects ranged from a low of 75.8% for Valeant Pharmaceuticals International Inc.’s toenail fungus treatment Jublia (efinaconazole) to a high of 89.3% for Durata Therapeutics Inc.’s antibacterial Dalvance (dalbavancin). The percentage of black/African American subjects ranged from a low of 1.9% in the ulcerative colitis trials for Takeda Pharmaceuticals USA Inc.’s Entyvio (vedolizumab) to a high of 11.4% for Cubist Pharmaceuticals Inc.’s antibacterial Sivextro (tedizolid).

“We are pleased that the FDA has followed through on the step in its action plan to make information about how new drugs work in women, minorities and the elderly available in a more publicly accessible, patient-friendly format,” American Heart Association Senior Government Relations Advisor Stephanie Mohl said in a statement.

“The proposed Drug Trials Snapshots are a move in the right direction and will help to give these populations and their health care professionals the information they need to make decisions about what treatment is best for them.” AHA said it is assessing how the agency can improve upon the snapshots and will submit written comments to the docket.

The Pharmaceutical Research and Manufacturers of America also intends to file comments.

It appears that CBER may be taking a slightly different approach than CDER in fulfilling its transparency obligation under the action plan.

A CBER spokeswoman said the biologics center is “developing a plan that will provide information through hyperlinks to specific information in the medical product reviews as stated in the action plan.”

Is More Transparency For Labeling Next?

Whether the snapshots’ detailed data on demographic subgroups ultimately make their way into product labeling remains to be seen.

FDA’s action plan includes an intermediate-term goal for the agency to identify potential methods to consistently communicate information on demographic subgroups in medical product labeling.

“Although we believe publishing demographic data collection and analyses on our Web site is an expeditious, simple and cost-effective way to share information, we acknowledge that stakeholders are also interested in how the labeling for medical products reflects this information,” the plan states.

FDA intends to work with industry, advocacy groups, risk communication experts (including the Risk Communication Advisory Committee) and other stakeholders to explore potential methods for communicating demographic analyses to the public, according to the plan.

Lisa LaMotta ([email protected]) contributed to this story.