Electronic clinical trial databases under development at FDA's Office of Women's Health will help sponsors design trials that account for gender and other demographic differences among patients, FDA Commissioner McClellan said.

"We are moving to a more fully electronic information environment for monitoring, encouraging and using useful demographic information in clinical studies," McClellan explained during the Oct. 29 "Clinical Trial Design For Sex Analysis" seminar in Washington, D.C. sponsored by the Society for Women's Health Research.

OWH is working with the Center for Drug Evaluation & Research and other centers at the agency to develop a Demographic Information and Data Repository that eventually will be a central database for trial protocols, study data and labeling information.

The Demographic Information and Data Repository was mandated in Congressional appropriations reports for FDA in FY 2002 and FY 2003. OWH is earmarked for $500,000 of its $3 mil. annual budget for the development of the repository.

"This rich electronic database will link all of the activities regarding protocol standards, standards setting, and electronic labeling," McClellan said.

"As a result of this initiative, FDA will have a better capacity to track and encourage the inclusion of women in clinical studies, as well as to provide more gender specific analysis to support labeling information."

"We'll also be able to more easily monitor differences in drug and dose response across different subgroups of patients in clinical trials without having to spend a lot of time and money each time we want to ask these kinds of questions," McClellan said.

"This system is being applied across all of FDA's different centers and will give us fundamentally better ways for collecting, storing, and managing the vast amounts of data that are submitted to us as part of product applications."

OWH expects the repository to be completed "in several years." Upon completion, the repository will not be limited to capturing gender demographics data but will also have the ability to capture data by race, age, geographic location and other demographic categories.

The development of the repository is part of a larger effort at the agency to standardize the collection of demographics data in order to improve drug safety.

In a draft guidance published Jan. 23, FDA recommends that clinical trial sponsors collect information on the race and ethnicity of participants using standard Office of Management & Budget categories (¹ Also see "Clinical Trial Race, Ethnicity Categories Should Match OMB’s, FDA Says" - Pink Sheet, 27 January, 2003., p. 12).

McClellan noted that FDA is also taking steps to "enable the clinical trial process to learn more about risks and benefits in particular populations, including demographic groups. This involves turning the explosion of information on pharmacogenetics into real knowledge that can improve the efficiency of product development."

The commissioner announced that FDA expects to release a draft copy of its guidance on pharmacogenomic data submissions Nov. 3. The guidance is "designed to encourage product developers to submit to us pharmacogenomic data as part of their clinical trials," McClellan said.

"This is information we know product developers want to develop, but in some cases don't want to submit to us, because in some cases nobody knows what the results of these analyses really mean, and they can perhaps raise false flags that product developers fear could end up slowing down the approval process," the commissioner said.

"So we are defining a research exemption for the submission of this data that will allow us to review it, and learn from it, along with the industry," McClellan said.

The guidance is expected to request, but not require, that sponsors voluntarily submit pharmacogenomic data that are generated for exploratory or research purposes. Such data would include pharmacogenomic testing programs that are intended to develop the knowledge base necessary to establish the validity of new genomic biomarkers.

In order to encourage and facilitate such studies, it is expected that pharmacogenomic information submitted through the voluntary process would not be considered by FDA for regulatory decision making on INDs or product approvals. The agency expects that most pharmacogenomics data that is currently being generated would qualify for the voluntary submission process.

The agency will co-sponsor a workshop on pharmacogenomics with the Pharmaceutical Research & Manufacturers of America, the Biotechnology Industry Organization and the Drug Information Association Nov. 13-14 in Washington, D.C. (² [A#00650410001], p. 3).

The guidance is expected to clarify the difference between valid genomic biomarkers and "probable" biomarkers.

FDA may define a biomarker as valid if it is measured in an analytical test system with well-established performance characteristics and there is an established scientific framework or body of evidence that elucidates the physiologic, pharmacologic, toxicologic or clinical significance of the test results. Under that definition, one example of a valid biomarker could be tests that distinguish allelic variants of the CYP450 2D6 enzyme for which the consequences for drug metabolism are well understood.

By comparison, FDA is understood to consider a biomarker "probable" when it appears to have predictive value for clinical outcomes but may not yet be widely accepted or have been independently replicated.

The guidance is also expected to clarify when pharmacogenomic data should be submitted with an IND or when it should be submitted with an NDA or BLA.

FDA is understood to want sponsors to submit pharmacogenomic test results with an IND if they constitute a known valid biomarker, if they will be used for decision making in any clinical trial, or if they will be used to support scientific arguments pertaining to the safety, effectiveness or dosing of the drug.

With an NDA or BLA, the agency is likely to ask sponsors to provide reports on pharmacogenomics studies intended to be used in the drug label or to support approval of the drug. The sponsor could provide an abbreviated report if it is not relying on or mentioning the study in the product label. An abbreviated report would also be appropriate for tests that represent probable biomarkers.

"This will complement all of our other efforts to get better information out of the data that are submitted as part of clinical trials, including our efforts aimed at helping companies perform better gender analysis of the data that they submit to us, so that we can learn as much as possible about the risks and benefits of drugs and how they may relate uniquely to women," McClellan said.

The Demographics Information and Data Repository is also part of FDA's broader electronic data management initiative.

In addition to touting the electronic repository for capturing pre-approval data, McClellan stressed the importance of using "twenty-first century technology to do a much better job of monitoring the safety and effectiveness of approved products in special populations, including women, after they are approved."

"We're working to develop active reporting systems, where we can receive more complete and reliable information in real time or near real time, by linking directly into electronic medical records and other information tools that are used in healthcare settings," McClellan said.

"Once more doctors are using electronic medical records, our hope is to make this kind of reporting a routine part of what they already do in their offices," the commissioner said.

"Once we have more of this information available in an electronic environment, we'll be able to perform more efficient post-approval studies using data pulled from electronic medical records, allowing low-cost clinical trials to be performed more quickly and easily in real-world medical settings."

The commissioner acknowledged that making progress in adverse event reporting is a "two-way street" and cited efforts like FDA's MedGuide and the development of the electronic label format, which "will make it possible to distribute real-time updates and consumer information." McClellan has previously called on health care providers to establish data sharing collaborations with the agency (³ [A#00650240015], p. 22).

FDA Genomics Guidance, Demographics Database To Improve Gender Analysis

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