IPEC - Fundação Oswaldo Cruz

Rio de Janeiro -Brazil

Women and Trials in Low and Middle-income Women and Trials in Low and Middle-income settings: the clinical investigator’s Perspectivesettings: the clinical investigator’s Perspective

August 6, 2008August 6, 2008

Beatriz Grinsztejn, MD,Ph.D

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)

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.

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

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

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

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

Recruitment-III

• Investigator’s fear of occurrency of pregnancy during the trial

• Easier to end up enrolling men

436

139

745

1571

53 (38.1%)

770 (49.0%)

196 (45.0%)

745 (100.0%)

0

200

400

600

800

1000

1200

1400

1600

1800

HPTN 052 ACTG 5175 ACTG 5221 ACTG 5208

Total of patients enrolled

Women enrolled

Women enrolled in HPTN & ACTG clinical trials – international studies

IPEC - FIOCRUZ

• 1986: HIV Care service outpatient/inpatient

• 1996: HIV-infected women cohort– 790 women enrolled– 25% (197) also participate in clinical trials

IPEC - FIOCRUZ

• 1999: 34 Clinical trials– Sponsered by:

• Pharmaceutical industry = 27• HPTN and ACTG = 7

• Patients enrolled– 678 (total)– 29% (197) women

Total of women who participated in clinical trials - IPEC

Participated in clinical trials

N(%)

No 593 (75%)

Yes 197 (25%)

Total 790 (100%)

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

Characteristics Results

Type of study – n(%) ARV – naïve ARV – experienced

64 (33.2%)129 (66.8%)

Age Mean (SD) Median

38.8 (9.8)38.0

Race White Others

95 (48.2%)102(51.8%)

Formal education >8 years <= 8 years

125(63.8%)71(36.2%)

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

Characteristics

Type of study

ARV – naïveARV –

experienced

T CD4+ count Mean (SEM) Median

242.7 (20.7)238.0

294.9 (18.7)254.0

Viral Load Mean (SEM) Median

423642.0 (143280.7)

110855.0

224983.2 (83767.5)

16709.0

*SEM = Standart error mean

Period of time

TotalNumber of

pregnanciesPregnant women

n %

1996-2008 764 101 86 11,3 (86/764)

1999-2008* 667 84 7711,5

(77/667)

1999-2008* 197** 4 42,0

(4/197)

Pregnancy rates

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

Factors associated with Women’s participation in clinical trials

IPEC/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).

Factors associated with Women’s participation in clinical trials

IPEC/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

Factors associated with Women’s participation in clinical trials

IPEC/Fiocruz (1999-2008)Univariate analysis

VariablesParticipated in Clinical Trials

No (N=565) Yes (N=102) pAge <35 36-45 >=46

55,1%30,1%14,8%

33,0%50,0%17,0%

<0.05

Formal education (>8 years)

40.6% 53.1% <0.05

Occupation (employed) 47.9% 34.3% <0.05

Lives in her own house 65.4% 78.0% <0.05

Living as married/married 38.6% 49.0% <0.10

Partner drug useNoYesUnknown

14.4%6.4%

12.4%

6.0%2.0%

12.0%

<0.05

Partner serologyNegativePositiveUnknown / not tested

23.1%40.5%12.9%

23.2%25.3%18.2%

<0.05

Factors associated with Women’s participation in clinical trials

IPEC/Fiocruz (1999-2008)

Univariate analysis Variables

Participated in Clinical Trials

No (N=565) Yes (N=102) p

Smoking No not anymore

53.9%23.8%

22.0%16.0%

<0.25

Alcohol use 59.9% 67.0% <0.25

Drug use 28.5% 18.0% <0.05

History of sexual abuse 20.6% 12.1% <0.05

The reason to be HIV tested issick/HIV+ family

39.7% 32.3% <0.25

Factors associated with Women’s participation in clinical trials

IPEC/Fiocruz (1999-2008) Logistic regression

Variables OR- CI(95%) p

Age <35 36-45 >=46

0,28(0,16-0,48)1,00

0,65(0,32-1,27)

0,000-

0,219Formal education >8 years <8 years

2,08(1,27-3,43)1,00

0,004-

Occupation employed unemployed

0,46(0,27-0,76)1,00

0,003-

Lives in her own house Yes No

1,71(1,00-3,01)1,00

0,057-

Living as married/married Yes No

1,89(1,11-3,24)1,00

0,019-

Factors associated with Women’s participation in clinical trials

IPEC/Fiocruz (1999-2008) Logistic regression

Variables OR- CI(95%) p

Partner drug useNoYesUnknownWithout partner

1,62(0,74-3,84)0,96(0,28-3,05)0,27(0,01-1,81)

1,00

0,2500,9440,254

-Partner serology*

NegativePositiveUnknown / not testedWithout partner

0,65(0,29-1,46)0,38(0,18-0,79)0,95(0,45-2,00)

1,00

0,3000,0110,894

-Drug use Yes No

0,64(0,34-1,17)1,00

0,160-

Sexual abuse history * Yes No

0,64(0,31-1,26)1,00

0,215-

*Likelihood ratio test for “partner serology” and “sexual abuse history” was 0.05 and 0.20, respectively.

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.

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

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

Thank you.