OMB Memo / Abbreviated Supporting Statement

U.S. Food and Drug Administration
Generic Clearance: Request for Data to Support Social and Behavioral Research
OMB Control Number 0910-0847
Gen IC Request for Approval

Title of Gen IC: A Positive Deviance Approach for Representing Women, Older Adults and Patients Identifying as Racial and Ethnic Minorities in Oncology Research

1. Statement of Need:

The purpose of this information collection is to identify practices, strategies and organizational contexts that allows sponsors to achieve top performance in recruiting underrepresented minorities in oncology clinical trials. The researchers will use a positive deviance approach to identify top performers.

The researchers will analyze pivotal trials supporting FDA approval of novel cancer therapeutics from 2012-2021 to identify top performing sponsors (“positive deviants”) on enrolling demographically representative trial populations. Trial participant demographics will be compared to those of the patients with the disease or condition targeted in a study by constructing a participant-to-prevalence ratio (PPR). Studies with at least a PPR of 0.8 will be considered to have adequate representation and will receive a score of 100%.

FDA is seeking OMB approval to conduct 24 interviews with respondents identified as positive deviants as described above. Each interview will last approximately 60 minutes. Transcribed data will be analyzed using a constant comparative approach.

Efforts to improve representation and diversity in clinical research span decades, yet disparities in enrollment persist. Studies show new cancer therapies are often tested in patients who are younger, healthier, and more likely to identify as White than real world patients with studied conditions. Women are under-represented in trials for some types of cancer, too. The barriers to enrolling representative trial participants have been well-described and include provider bias, patient mistrust of a health system with a long history of racism, trial eligibility criteria, and financial barriers, among others. Provider behaviors and strategies certainly play a role; some evidence suggests that Black and Latinx patients may be less likely to be asked to participate in studies than White patients.

When trial participants do not represent the age, sex, racial or ethnic identity of patients for whom treatment is indicated, clinicians, payers and patients can be left wondering how to apply trial findings for themselves and patients. This can harm patients through several mechanisms. In some cases, when the risks of a treatment in real-world patients are substantially higher than trial participants, then using those treatments in routine practice may result in greater harm than benefit. In other instances, clinicians may avoid using new treatments in certain patient groups (such as older patients), even though they may benefit. Further, inadequate inclusion can exclude certain groups from the benefits of research, especially having treatments guided by evidence applying to patients like them. Such exclusion can risk harm exposure and lost opportunities to pursue more effective therapies.

Previous research evaluating publicly available data about the numbers of historically underrepresented groups included in pivotal trials supporting novel cancer therapeutics that were approved by the FDA from 2012 to 2017, shows some trials are better than others and some companies are consistently better than their peers at enrolling representative samples. We propose studying what distinguishes exceptional performing sponsors and trials from their peers on specific measures, using a positive deviance approach, to determine shared behaviors, strategies and contexts enabling them to perform better that can be generalized and implemented by the broader research community to produce similar results.

2. Intended Use of the Information:
   
   

The objective of the proposed work is qualitative understanding of the factors which lead to adequate representation of minority groups in oncology clinical trials. The aim is not statistical representation, but instead to gather information from multiple sponsors. The goal of the project is to publish manuscripts to disseminate information to the scientific community about strategies to increase enrollment of unrepresented groups in oncology clinical trials. The data collection proposed here will not be directly used for making policy or regulatory decisions.

3. Description of Respondents:

Study respondents will be staff and administrators from organizations who sponsored pivotal trials supporting novel oncology drug approvals by the FDA between 2012 and 2021 who have successfully recruited underrepresented minority groups and are identified as positive deviants as described above. These sponsors are all from industry, comprised of pharmaceutical and biotechnology companies.

Respondents will not be segmented; that is all respondents will be analyzed in a single group and not segmented into subgroups.

4. How the Information is Collected:

After identifying top performing sponsors through an analysis of the scientific literature, the researchers will send invitations to potential participants by e-mail. Before each interview, the researchers will obtain oral consent from each participant. Prior to each interview, staff and administrators will complete a brief demographic survey and general questions about challenges relating to diversity, equity, and inclusion in oncology clinical research. The researchers will use a standardized interview guide that begins with a general question:

“In the last 3-5 years, what are the major initiatives your group has undertaken to enable representation of women, older adults and or Asian, Black and LatinX identifying patients in trials;”

The interviewers will then ask respondents to describe specific instances of difficulty and success in research execution and experiences monitoring progress and sustaining efforts. Interview responses comprising stories and vignettes will be encouraged.

5. Confidentiality of Respondents:

The following procedures will be used by the Yale research team to ensure participants identity and information will be kept secure to the extent permitted by law before, during, and after fielding.

1. Full names of the participants will be used only for recruitment and scheduling purposes and will not be included on any interview materials provided to the FDA (e.g., typed lists of participants); instead, each participant will be assigned a unique ID by which they will be referred. All information obtained about participants during the conversation will be held in confidence and accessible only to the research team.

2. Screening-related information will not be tied to any PII, but identified and matched by the assigned unique ID. For scheduling information, this will be limited to first name, last name, email, and phone number(s).

3. Zoom audio recordings will be stored on a server only accessible to study staff with research permissions. FDA will not receive any audio recordings. Written excerpts, summaries, and written reports will not contain any PII.

4. Analyses will be conducted on the aggregate. Any individual responses, such as exemplar quotes used in reporting, will not be attributed to specific participants.

The oral informed consent procedure will contain language that notifies participants of the audio recording via Zoom. Before each interview begins, the interviewer will confirm consent by receiving verbal affirmation from the participants to record the session.

The following statement is included in the oral consent email script: “Please understand your participation is voluntary and you have the right to withdraw your consent or discontinue participation at any time without penalty.”

6. Amount and Justification for Proposed Incentive:

No incentive is provided.

7. Questions of a Sensitive Nature:

The Yale research team will not ask any sensitive questions in the interviews. Participants will be asked to describe their professional experience, in general, with respect to managing clinical trials of oncology therapeutics. Respondents will be told that they may skip questions that they do not want to answer or may stop participating at any time.

8. Description of Statistical Methods:

Yale does not plan to use statistical methods in this qualitative study, but rather qualitative analysis methods appropriate for interview data.

Descriptive characteristics on sponsors will be recorded in a standardized data collection form. Transcribed data will be analyzed using a constant comparative approach. An initial code list will be used to organize transcripts of the first 2 interviews and then iterated from subsequent ones. Using the final code, 2-3 researchers will independently code all transcripts and meet as a group to code in joint sessions, achieving consensus and assigning codes to observations by a negotiated group process. Specific analysis will be conducted to identify distinct themes shared by high performers on specific measures. Findings will be characterized and disseminated through a series of high impact peer-reviewed journal articles and presentations. Lessons learned from low performers will also be noted. The researchers plan to use NVivo to analyze interview data.

9. Burden Hour Computation:

Type/Category of Respondent	Number of Respondents	Participation Time (hourly)	Burden (hours)
Interview participant (email response)	24	0.02 (1 minute)	.4
Interview participant (scheduling)	24	0.07 (4 minutes)	1.6
Interview participant (consent, demographic survey, and interview)	24	1 (60 minutes)	24
Total	24		26

Researchers estimate that it will take one minute to respond to the email and may take up to four additional minutes to schedule an interview time by phone. The researchers also anticipate that it will take five minutes to obtain oral consent, five minutes to complete the demographic survey, and 50 minutes for the remainder of the interview.

10. Date(s) to be Conducted:

Yale plans to conduct interviews between July and August 2023.

11. Requested Approval Date: July 2023

12. FDA Contacts:

Program Office Contact	FDA PRA Contact
Julie Schneider Oncology Center of Excellence U.S. Food and Drug Administration julie.schneider@fda.hhs.gov 240-402-4658	JonnaLynn Capezzuto Director, Paperwork Reduction Act Staff Office of Operations U.S. Food and Drug Administration Jonnalynn.capezzuto@fda.hhs.gov 301-796-3794

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