IPEC - Fundação Oswaldo Cruz Rio de Janeiro -Brazil

1. IPEC - Fundação Oswaldo Cruz Rio de Janeiro -Brazil Women and Trials in Low and Middle-income settings: the clinical investigator’s Perspective August 6, 2008 Beatriz Grinsztejn, MD,Ph.D

2. Background • HIV disproportionately affects women in developing countries • Underrepresented in poor-resource regions (McGovern et al, 1994; Allen 1994; Mills et al, 2006; Kapoor 2004; Zuniga et al, 2007; Wassenaar et al, 2007)

3. Background • If women are to benefit from prevention and therapeutics interventions, they must participate in the trials in a sufficient number to allow appropriate gender-specific evaluation of efficacy and safety.

4. Background • In general, there is a paucity of clinical trials going on in the RLS, where the greatest burden of the epidemic exists • The majority of products in the market were developed without adequate representation of RLS population in the trials. The generalisability of trials results to these populations may be compromised • This affects both men and women. Women’s social inequality in these societies makes it even worse for them

5. Women in HIV Clinical Trials • Willingness to participate, perceptions and concerns about clinical trials in poor-resource settings: • Studies show that women want to participate in clinical trials (qualitative analysis, interviews with women participating in prevention studies) • The two most common motivations for participating in a trial were "getting tested for HIV" and "doing something good for women's health.“ • Repeated, voluntary counseling and testing, knowledge of HIV status, and heightened awareness of sexual and reproductive health reshaped study participants' approaches to sexual relationships and AIDS Tharawan et al, 2001; Coulibaly-Traoré et al, 2003; Stadler et al, 2008

6. Recruitment • HIV-related stigma • Studies have shown that stigma is a measurable barrier to accessing general HIV care; thus, it would be expected that it may also serve as a barrier to participating in a clinical trial. • Confidentiality issues • Employment opportunities • Family relationships • Social acceptance

7. Recruitment-II • Ability of women to meet the ongoing and multiple requirements of trial participation • Employment issues • Childcare • Partner health status • Disclosure • Financial resources • Fertility desires • Social representation of motherhood

8. Recruitment-III • Investigator’s fear of occurrency of pregnancy during the trial • Easier to end up enrolling men

9. Women enrolled in HPTN & ACTG clinical trials – international studies

10. 1986: HIV Care service outpatient/inpatient 1996: HIV-infected women cohort 790 women enrolled 25% (197) also participate in clinical trials IPEC - FIOCRUZ

17. IPEC - FIOCRUZ • 1999: 34 Clinical trials • Sponsered by: • Pharmaceutical industry = 27 • HPTN and ACTG = 7 • Patients enrolled • 678 (total) • 29% (197) women

18. Total of women who participated in clinical trials - IPEC

19. Characteristics of women who participated in clinical trials – IPEC (N=197)

20. Characteristics of women who participated in clinical trials – IPEC (N=197) *SEM = Standart error mean

21. Pregnancy rates *Time period in which HIV clinical trials have been conducted in IPEC/FIOCRUZ. **Total of women who participated in HIV clinical trials.

22. Factors associated with Women’s participation in clinical trialsIPEC/Fiocruz (1999-2008) Objective: To evaluate the potential factors associated with women’s participation in clinical trials. Outcome variable: “Did the woman participate in clinical trials? Yes or No”. Covariates: age,ethnicity, years of formal education, occupation, monthly familiar income, lives in her own house, lives as married//married, partner drugs abuse, partner HIV serology, receive any support, number of alive children, children with HIV/AIDS, tobacco use, alcohol use, drug abuse, sexual abuse history, domestic violence history, reason to be HIV tested (sick/HIV+ family).

23. Factors associated with Women’s participation in clinical trialsIPEC/Fiocruz (1999-2008) Statistical analysis: Univariate analysis: The χ2 test Variables for which the significance level was ≥ 0.25 and variables of known biologic importance were considered in the initial Logistic regression model. Multivariate analysis: Logistic regression We begin with a full model containing all of the selected variables. The Wald statistic and Likelihood ratio test were used to check the importance of each variable included in the model. The following rules were used in evaluating if a variable was retained in the final model: 0.7 < Odds Ratio < 1.3 : p-value ≤ 0.1 Odds Ratio ≤ 0.7 or Odds Ratio ≥ 1.3 : p-value ≤ 0.2

24. Factors associated with Women’s participation in clinical trialsIPEC/Fiocruz (1999-2008)Univariate analysis

25. Factors associated with Women’s participation in clinical trialsIPEC/Fiocruz (1999-2008) Univariate analysis

26. Factors associated with Women’s participation in clinical trialsIPEC/Fiocruz (1999-2008) Logistic regression

27. Factors associated with Women’s participation in clinical trialsIPEC/Fiocruz (1999-2008) Logistic regression *Likelihood ratio test for “partner serology” and “sexual abuse history” was 0.05 and 0.20, respectively.

28. Conclusion • Women with more years of formal education, who live in their own home, in marital relationship and those who have a non drug use partner are more prone to participate in HIV clinical trials. • Younger women, those who are employed and who have a HIV positive partner have a lower chance to participate in HIV clinical trials, as well as that women who reported drug use and sexual abuse history.

29. Final Remarks • More research is needed in order to improve the understanding of individual and system barriers to clinical trials’ participation of women in RLS • Investigators directly involved on the recruitment must be sensitized about the importance of women’s participation in clinical trials and potential strategies to overcome this barriers must be discussed with the team before the start of each study

30. Final Remarks • Strategies of recruitment and retention must be individualized considering social and cultural aspects of each context • Involvement of the affected communities since the beginning is crucial

32. Thank you.