As most of you know, the FDA is working on their guidance doc: Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies. In June, they released the latest version, which brings more clarity and direction for the content and objectives of Diversity Action Plans. It’s a step forward in the pathway to making these plans a mandated requirement for drug development, which will ultimately impact and influence the commercialization goals for drug and device developers. The updated guidance is now available and open for a 90-day commentary period.

The guidance doc specifies that a Diversity Action Plan will be required for a clinical investigation of a new drug that is a phase 3 study, or as appropriate, another pivotal clinical study of a drug (other than a bioavailability or bioequivalence study).

Certain sections of the FD&C Act require that sponsors submit a Diversity Action Plan that specifies goals for clinical study enrollment, and states that such goals must be disaggregated by the race, ethnicity, sex, and age group demographic characteristics of the clinically relevant population. When developing these goals, sponsors should consider the distribution of the intended use population according to these demographic characteristics.

Sponsors should consider whether certain demographic groups (e.g., older patients, pediatric patients, females, a particular race or ethnic group or combinations thereof) may have a different response to the medical product—either differential effectiveness or safety (e.g., based upon differential pharmacokinetics (PK), pharmacodynamics (PD), or due to possible differences in susceptibility to specific adverse events of concern for a drug or medical device), or due to differential presentation of the disease or condition. In some cases, it may be necessary to increase the proportional enrollment of a certain population in the clinical study to evaluate outcomes of interest or other clinically relevant factors in that group.

ELEMENTS OF A DIVERSITY ACTION PLAN (from the Summary of the DAP) (starting at line Appendice 1, p. 22)

The cover letter accompanying a submission that includes a Diversity Action Plan (DAP) should alert the FDA that the submission includes a DAP and denote whether the DAP is new or modified. Indicate in the cover letter accompanying a new or revised DAP, “DIVERSITY ACTION PLAN-Initial” or “DIVERSTY ACTION PLAN- Revised,” respectively, written in large, bolded type.

The DAP should contain a clear and concise description of the required elements of the DAP, with limited cross-referencing of previously submitted documents to facilitate review. In most cases the DAP should be succinct, its length generally not exceeding 10 pages, excluding references.

  1. TITLE PAGE

The title page of the DAP should include relevant administrative information:

  • Medical product name.
  • IND/IDE number (if applicable), and/or other relevant submission information (e.g., to identify previous Q-submissions or marketing submissions for the medical device).
  • Proposed indication or indications for use statement and intended use.
  • Clinical study identification information (e.g., NCT number, title, study ID).
  • DAP version number and date.
  1. ENROLLMENT GOALS

Enrollment goals must be disaggregated by:

  • Race (sponsors should list goals for each category according to FDA guidance for reporting race);
  • Ethnicity (sponsor should list goals for each category according to FDA guidance for reporting ethnicity);
  • Sex (sponsors should list goals for each category according to FDA guidance for reporting sex);
  • Age group (sponsors should list goals for clinically relevant age subsets according to FDA guidance).
  1. RATIONALE FOR ENROLLMENT GOALS

Diversity Action Plans must include a rationale for the enrollment goals. To meet this statutory requirement, a sponsor’s rationale must include sufficient information and analysis to explain how the sponsor determined its enrollment goals. Thus, a sponsor’s rationale for enrollment goals should include information necessary to understand the disease or condition including natural history, risk factors, etc. If conducting several clinical studies to support a single marketing submission and opting to specify enrollment goals across the planned clinical studies, sponsor must indicate how the individual clinical studies are intended to contribute to the stated enrollment goals.

Additionally, for drugs the rationale should include:

  • Data and information that describe the potential for differential safety and effectiveness of the investigational drug across the clinically relevant population (e.g., differences in pharmacokinetics [PK]/ [pharmacodynamics [PD]).
  • Data regarding genetic differences in PK, PD, safety, or effectiveness (e.g., genetic variations, which may vary based on ancestry, that impact drug metabolism or susceptibility to adverse reactions).
  • As applicable, the relevancy of other population-level or individual characteristics that available data suggest have an impact on the clinical outcomes (e.g., socioeconomic status, geographic location, comorbidities).

The DAP should include citations for the sources of data and information upon which the enrollment goals are based.

  1. MEASURES TO MEET ENROLLMENT GOALS

The DAP must include an explanation of how the sponsor plans to meet the specified enrollment goals:

  • The DAP should include a description of the enrollment and retention strategies for the study population (focus is on measures that address diversity and representativeness of participants enrolled in a specific clinical study).
  • The DAP should include a description of the plan to monitor enrollment goals during the conduct of the clinical study to ensure that goals are met.