Women’s Global Health Scholars (GWHS) Program Nancy Padian, PhD, MPH Women’s Global Health Imperative Research Triangle Institute and the University of California

Program Summary Equip female health scientists from around the world – at doctorate, post-doctorate and junior faculty levels – with the tools, skills and networks needed to advance careers and assume leadership positions Special focus on women in academia, and the biases, hierarchies and structures they confront

Curriculum Draws from other successful leadership training models: –CHESS curriculum of the Association of Commonwealth Universities –Executive Leadership in Academic Medicine –Public Health Institute’s International Family Planning Leadership Program Through interactive, dynamic process scholars identify barriers in own institutions and settings, and strategies to overcome them

Program Structure and Content Sept and Sept – 1 week each Hands-on workshops: –Strategic career planning –CV organization, strengthening, and maintenance –Writing for publication –Grants development and review –Research administration (including budgeting) –Negotiation skills –Networking with leaders, donors, colleagues –Multidisciplinary collaboration –Navigating academic politics and hierarchies Quarterly on-line educational sessions Monthly peer mentoring conference calls

Participants In women were selected from a competitive pool of nominees to participate in the program –Africa: Kenya, Malawi, Tanzania, South Africa, Uganda, Zimbabwe, Botswana – Asia: China, India, Vietnam –Eastern Europe: Turkey, Georgia –Latin America: Brazil, Argentina, Peru Multidisciplinary

Success Indicators 8 Competitive grants approved for funding 6 Grants completed for submission 36 Papers published in peer-reviewed journals 24 Papers submitted for publication in peer- reviewed journals 2 Young Investigators Awards 24 Abstracts accepted for posters and presentations at national and international meetings

Other Successes Replication of training with junior scientists in Argentina Ongoing regionally-based peer mentoring support groups A cohort of mentors for the next generation of scholars Individual life-altering experiences

Ethical challenges in a randomized controlled trial of diaphragms and gel to prevent HIV (the MIRA trial)

MIRA Study Design All women receive risk reduction counseling, free male condoms and diagnosis and treatment of curable STIs Women were followed quarterly for months +

MIRA Trial Sites Total n = 5045 UZ-UCSF Harare, Zimbabwe n=2502 PHRU Soweto, South Africa n=1028 MRC Durban, South Africa n=1515

Main results from ITT (n=4948) HIV Incidence rate Relative Hazard (95% CI) All Sites (0.84 – 1.32) Harare (0.83 – 1.74) Durban (0.69 – 1.31) Soweto (0.60 – 1.87) intention-to-treat, results according to random assignment:

Three challenges Study product distribution during and after the trial Nature of the control group: interpretation and generalizability of results Standard of care for seroconverters

Study Product Distribution As part of informed consent at entry, women were told “you will receive a diaphragm at the end of the study” Two challenging time points –As individuals exit the study (rolling recruitment), before results were known –After data were analyzed and results made public

Pros and Cons of product distribution during the study Take it back at final visit Implicit message that it works for HIV and contraception –reduce condom use? Available outside study –encourage use with OTC spermicide? Let them keep it until data are analyzed Women will be disappointed Could affect likelihood of coming to final visit and loss to follow-up Could send a wrong message to women who continue in the study

Discussion with CABs, participants, TAB, ethicist Should we: Wait to give a diaphragm and gel to women if and when we have a positive trial result? OR Give them to women at their last visit with significant education and counseling  All women will be given a generous supply of condoms at their last study visit

Pros and Cons of product distribution after the results were known (both arms) “Require” that they return the product Implicit message that it works for HIV and contraception –reduce condom use? Available outside study –encourage use with OTC spermicide? Up to each women Would necessitate contacting each participant Products do not cause harm

Community verdict = offer products, don’t require return Women are intelligent enough to decide for themselves. –Patronizing to think otherwise Communities and participants would feel betrayed by study if the investigators went back on their promise

MIRA solution As individuals exit, offer study products after an additional informed consent including counseling about efficacy for pregnancy and disease prevention through: –Close-out consent form with initialed statements –Comprehension quiz At the end of study, group meetings to explain and disseminate results; same procedure as exiting during the study

Close-out consent, sample statements Replens  is a gel used to lubricate the vagina, and it is NOT a spermicide. Using Replens  with the diaphragm is NOT a proven method of preventing pregnancy. Initials: ________ Condoms are currently the only proven way to prevent HIV and other STIs. Initials: ________

Diaphragm uptake at closing Proportion of participants interested in taking a diaphragm home at closing: 73.5% of diaphragm & gel arm ppts 47.4% of condom arm ppts Chi-square for difference highly significant (p<.0001)

Compared to whom??? Interpretation and generalizability of results

MIRA bottom line In the context of a comprehensive HIV prevention package offered to all participants, the trial found no additional protective benefit against HIV infection from providing the diaphragm plus lubricant in the intervention arm.

What MIRA could not assess… Whether a diaphragm is as good as a condom Whether a diaphragm is better than nothing

Most vulnerable women Majority of women are at risk because their male partners do not use condoms Current trial results may not be generalizable to them Likely not to participate (male partner participation is implicit) Condom use during the study may not reflect “real life” How to target, recruit and enroll women whose partners will not use condoms (e.g. sex workers with low levels of condom use with steady partner)

Sustainability of high levels of condom use beyond a trial (different comparison during and after) Survey of participants enrolled in an RCT of N-9 in Cameroon 14 months after study participation Attributable to a change in behavior or in reporting? During studyPost-study % of acts with condoms % of ppts reporting consistent condom use Source: Wong et al.

Reconsider standards of condom counseling in the trial (both arms) and beyond Community standard vs. enhanced counseling? More difficult to assess the intervention –Attenuation of power Uncouple condom counseling from intervention protocols: e.g. as part of VCT prior to enrollment? Consider programs that sustain condom use in the community after the study

Consider alternative study designs? Head-on comparison of intervention to condom (true equivalence)? Condom “run-in”, or otherwise recruit women whose partners will not consistently use condoms

MIRA SOC program for sero-converters* during the trial SOC visit by study staff (counseling, support groups, OI tx, staging, referrals) Access to continued psychosocial support and clinical services through referrals or partnerships with community organizations/ facilities Transition all MIRA seroconverters into the National ARV Programme in Zimbabwe or South Africa before the end of the trial period (*In Zim, HPV sub-study provided screening, care and treatment for infection and disease)

What happens when the trial is over? (comparable to screening out seropostives at entry) Who pays? Append to existing programs (state, faith-based, other) –Quality as high as that which was provided during the program? –Only conduct trials where such programs exist as a certain level of quality? May mean not conducting trials where results most needed Other solutions?