Women s Inclusion in HIV Clinical Research: Challenges and Successes

Transcription

1 Women s Inclusion in HIV Clinical Research: Challenges and Successes Mary Allegra Cermak ACTG Community Coordinator Sharon Maxwell Henkel Women s HIV Research Collaborative Co-Chair Annet Davis-Vogel Women s HIV Research Collaborative Co-Chair Katie Osterhage Project Manager, Legacy Project

2 Learning Objectives 1. Learn about successful recruitment strategies for engaging women in HIV clinical research 2. Learn about successful engagement strategies in other community-based activities and groups that could be applied to engage women in an HIV clinical research setting 3. Identify strategic partnership areas for exchanging knowledge and skills between research sites and community-based organizations and IADS-service organizations who serve highly impacted women,

3 What are the issues? Women s participation is crucial for understanding sex differences in disease therapy, prevalence and response Lack of enforceable ratios for recruiting and retaining a certain number of women in clinical trials Institutional reluctance to require certain percentages of women enrolled and retained in clinical research studies Slow accrual and retention challenges for enrolling and retaining women s participation in clinical studies

4 Barriers to women s participation in HIV clinical research : Length of visits Complexity of studies Competing priorities Studies not solving women s perceived problems Current substance use User friendly culture Not a lot of primary care patients at CRS Cultural impressions No support system Protocols directly exclude women Many, many more

5 Successful strategies for engaging women in HIV clinical research Dedicated research recruiter Patient registry reviewed on routine basis Travel reimbursement (cab, gas or bus pass) Child care reimbursement Having a woman PI Working with local HIV/AIDS case managers Providing support groups Establishing relationships with agencies that focus on women and girls Support educational forums

6 Successful strategies for engaging women in HIV clinical research Social workers promote trials at outreach events Hire staff that fits the demographics of the area Actively engage with other networks in the area Schedule trial visits with clinic visits Flexible scheduling Develop a structured recruitment plan Work with local CABs Ethnically appropriate advertising Encourage women s participation in the CAB Recruit through Ryan White clinics

7 COMMUNITY ENGAGEMENT PLAN Setting the Stage to Recruiting &Enrolling Women in Research Trials

8 Engaging Women in Research Trials Begin with the end in mind Identify stakeholders: leaders within the community targeted for the project, CBOs to become community partners, identify informal gatekeepers Engage early & often with the community representatives Engage underrepresented groups and those with multiple perspectives Stakeholders are a valuable source of information & will link you to other stakeholders, CBOs, neighborhood leaders Engaging women in research trials is a collaborative process that MUST include formal & informal women leadership within the community, especially including women from the targeted population for enrollment the research trial.

9 The Key Components of a Community Involvement Approach: Development & implementation of a community involvement plan Establish a community working group/community advisory board Develop & implement a realistic appropriate community involvement strategy Research team provides ongoing technical assistance and training & educational materials CWG/CAB involved at every level of the research design

10 Development & Implementation of a Community Involvement Plan Developing a network of community leaders Established Community advisory groups Selecting individuals as consultants Identifying leaders to participate in the planning and design of the trial

11 Community Advisory Board (CAB) CABs are: A group consisting of volunteers from communities affected by particular issue (HIV, violence, breast cancer, etc.) A group working in partnership with the researchers (scientific leadership) to foster the creation, promotion, & implementation of the scientific research related activities. The research team & CAB are collaborators, working together in a mutually respectful, pro-community manner.

12 Recruitment Strategies If possible begin with implementing an ethnographic approach: learn about the attitudes, behaviors and norms regarding the targeted population of women: example: when recruiting women at increased risk for HIV due to drug use & sexual practices spending extensive times in locations where women using drugs congregated, engage in conversation with the women, ask about interest in research trials, what would be barriers to join a trial. Need to implement a harm reduction approach, meeting enrolled women at a convenient location & escort them to study site include reimbursement for transportation in addition to compensation Recruiting women in vaginal microbicide trial recruited at beauty shops, day care centers, nail salons, inquired about need for child care at study visit, had staff on hand to babysit, reimbursed for taxi when needed

13 MARS? NEEDS WOMEN: WE NEED TO SEE OURSELVES IN RESEARCH Trials which include women may provide more accurate data and trust from those who will benefit from the research According to the NIH inclusion guidelines, principal investigators (PI) are to propose their plans for the inclusion of women, minorities, and children in their research proposals or justify their exclusion (National Institutes of Health, 1997; National Institutes of Health, 1998; National Institutes of Health, 2001).

14 Questions Only Women Can Answer Hormonal data Dosing information; higher rates of adverse drug reactions Differences in any major system response Sex-specific prevalence Sex-specific diagnosis and treatment patterns Identification of proportions of women included in past studies for the target indication Identification of any known clinically significant sex differences in outcomes related to either safety or effectiveness

15 Why? women are underrepresented Possible reasons given: Inclusion criteria Old issue: Contraception requirements Newer problem: Study product risk for women of reproductive potential Burden of study procedures Site recruiting practices and support Claim that recruitment of women will delay enrollment

16 The USUAL Reasons The primary reasons for lack of participation by minority groups is the failure to invite them to participate, to provide accessible sites for participation, and failure to overcome barriers such as childcare arrangements and transportation costs. Time limitations Transportation Child care Lack of information NOT ASKED!!! WHAT DO YOU THINK?

17 Frequent Inclusion Criteria Limitations Contraception requirements: standardized, driven by package insert/ib of product being used Study product risk to women of reproductive potential: Now in development some guidance for reviewers, teams and investigators, to improve # studies allowing women. Will limit enrollment of women into trials

18 Ethical Considerations on Pregnancy Criteria Whose safety is main concern? Participant, potential fetus, investigator, drug manufacturer Who should make decision? Investigator, IRB, participant WHAT DO YOU THINK?

19 What Sites Need to do in Recruiting Practices and Support Creative Outreach to affected populations Build awareness of trials, trust, involve personal physicians, accessibility of study site Create trials that are relevant: a need to engage community in discussions Provide peer support to engage in research, involve community organizations in spreading the word WHAT DO YOU THINK?

20 Women in ACTG Trials Accrual has improved, mostly due to non-us enrollment. Domestically: stable, but low enrollment New challenges with interventions used in HIV eradication and other trials Need to update and support site recruitment practices

21 Planning for Success Target a specific research area Consider regional epidemic data Look for other local successful research enrolment in area Ask for advice from other research outreach experts

22 Energy From the Community A member of the WHRC and ACTG community spearheaded a letter to the network leadership on the subject of recruitment of women. This led to follow-up calls and meetings on barriers to women and how to move forward on developing a best practices document. Network leadership suggested working with the evaluation committee to identify site issues, prioritize target areas. Another suggestion was to hold consultation calls or meetings with outreach workers at sites having difficulties and suggest strategies to improve enrollment.

23 No Simple Fix Small or even moderately sized studies are unlikely to be able to answer questions about sex effects Lack absolute numbers of women needed Example: n=50, even 50% women is only n=25 Key: not the relative number (% of women to men), but the absolute/raw number of women that drives statistical power Some large (phase III/IV studies) have identified sex by treatment interaction effects; SDAC SOPs reflect NIH policies to address these directives Area of opportunity for study portfolio without large studies Cross-protocol analyses (DACS/NWCS) Precedent: DACS Differences by age among women in the response to initial highly active antiretroviral therapies (HAART): Metaanalysis from clinical studies submitted to the FDA and the AIDS Clinical Trials Group-sponsored studies (aging in women across ACTG studies) BUT even % of women may impact trust and perception of trial

24 Results in Other Research Areas The Prevention of Pelvic Infection (POPI) a chlamydia trial in young women over 2 years the study recruited 2526 women, of which many were ineligible. students met with young women in classrooms to discuss enrollment in the trial Project DC-HOPE, one project within the NIH-DC Initiative to Reduce Infant Mortality in Minority Populations in the District of Columbia used an Audio Computer-Assisted Self-Interview to recruit; retention strategies included financial and other incentives, regular updates of contact information with targeted recruitment and retention strategies, minority women will participate at high rates in behavioral clinical trials.

25 And in Other Studies Sister Study - Recruitment of 50,000 female participants between the ages of representing the diverse demographic populations in the United States and Puerto Rico was done over a five year period utilizing a range of community based efforts to nationally endorsed campaigns. Sources of information most often used in recruitment were: Word of mouth or the one-on-one, trusted source approach such as reaching families and sisters affected by breast cancer; breast cancer support groups; study participants; local gatekeepers and attendance at local and national women s events Approaching organizations such as churches, hospitals, mammography centers waiting areas; primary health care associations; unions and trades organizations; Media relations and paid advertisement campaigns via direct mail, mass s, and outlets such as television, web, radio, newspapers and magazines. Note: This study did not involve clinic visits

26 Some Literature on Sex Differences in HIV Moore AL (JAIDS 1999) Gender differences in virologic response to treatment in an HIVpositive population: a cohort study (PMID ) Conclusion: Women may achieve virologic suppression at a faster rate than men and have a more durable response. Further research should examine these responses in conjunction with clinical outcomes, because gender differences in virologic response may ultimately be of little relevance if clinical outcomes are similar. Poundstone KE (AIDS 6/ ) Differences in HIV disease progression by IV drug use and by sex in the era of HAART Disease-free survival time was extended with the use of HAART, but these gains were not equally distributed by sex and IDU in our cohort. Meditz AL (JID /15) Sex, race and geographic region influence clinical outcomes following primary HIV-1 infection (PMC )- AIDRIP Sex and race did not affect responses to ART after 6 months (P >.73). Women were fold more likely than men to experience >1 HIV/AIDS-related event (P <.001). Conclusion: Despite more favorable clinical parameters initially, female HIV-1- seroconverters had worse outcomes than did male seroconverters. Hawkins C (AIDS 2011) Sex differences in ART outcomes among HIV-infected adults in an urban Tanzanian setting (longitudinal cohort analysis PEPFAR) Men had higher rates of death, immunologic non-response and LFU

27 LET S TALK Why would you enroll in a study? What would you tell Recruiters Outreach workers Your own doctor

28 THANK YOU!

29 EVALUATIONS