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Women’s Participation in Clinical Trials Are we POWERED to meet the Challenge?

Women’s Participation in Clinical Trials Are we POWERED to meet the Challenge?. Dr Sharon Walmsley Professor of Medicine University of Toronto, Canada. On behalf of the Score Card Working Group. Catherine Hankins Judith Currier

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Women’s Participation in Clinical Trials Are we POWERED to meet the Challenge?

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  1. Women’s Participation in Clinical TrialsAre we POWEREDto meet the Challenge? Dr Sharon Walmsley Professor of Medicine University of Toronto, Canada

  2. On behalf of the Score Card Working Group • Catherine Hankins • Judith Currier Supported by the team in the Office of the Chief Scientific Advisor • Diane Addison • Tania Lemay • Nicolai Lohse • Adam Trotta

  3. Randomized Controlled Clinical Trials Most rigorous scientific means to evaluate and compare therapies with respect to efficacy and side effects Process of randomization and blinding eliminates bias Requires large numbers of participants for diseases where there is established therapy

  4. Randomized controlled clinical trials To apply the results to clinical practice, the participants in the study must be similar to your population Is sex an important variable for trials of antiretroviral drugs?

  5. Why might there be sex differences in response to antiretrovirals Potential for differences in drug absorption, metabolism, excretion Body size Body fat content Concentration of enzymes responsible for drug metabolism Hormonal effects Gonadotropins and circulating steroids Hormone replacement therapy Pregnancy Oral contraceptives (drug interactions) Attitudinal Adherence Delays in Initiation

  6. What is the problem with the data in clinical trials of HIV therapies? Women are under-represented Studies are under-powered for gender comparison

  7. Gender Bias in Clinical Trials Cochrane Controlled Trials Register 1990-2000 n=49 studies: 15,612 participants Mean proportion of women 12.25% None analyzed by sex Pardo, World AIDS, 2002, Abstract WePeB5964

  8. Cohort studies of ARV Confounders must be adjusted for Age Race Education Baseline CD4, VL Hepatitis C coinfection Adherence

  9. What would it take?Sample Size Calculations to Detect a 50% Reduction in 2-Year Failure Rates Between Women and Men (1-beta=.8, alpha=.025) % accrual of women 10% accrual 3500 15% accrual 3000 20% accrual 2500 2000 1500 1000 500 0 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 TotalSampleSize Failure Rate in Women J Currier et al., VIII Int Conference on AIDS, Amsterdam 1992, Abstract 4705

  10. Complications of ARVIs it different by sex? Sex Differences Noted Pancreatitis Rash Lower risk of TG increase Higher rates of low HDL women Fat Accumulation and Lipoatrophy Phenotype Hepatic steatosis and lactic acidosis Higher in women

  11. Sample Sizes Required to Detect 2-Fold Differences in Toxicity Rates Between Men and Women J Currier et al., VIII Int Conference on AIDS, Amsterdam 1992, Abstract 4705

  12. Women’s ScorecardMethodology Search of HIV treatment naive phase III clinical trials received by www.clinicaltrials.gov on or after 01/01/2000 Published data/abstracts for completed trials investigated for the inclusion of women/girls Principal investigators contacted for ongoing studies

  13. Women’s ScorecardMethodology Excluded Pediatric only (<= 12 years) Only men or only women Data collected age, sex, enrolment number, study location, sponsors, contraception criteria, pregnancy exclusion criteria, year of study start

  14. Women’s ScorecardMethodology Outcomes Sex (% female participants) Adolescents ( % 13-18yr) (or 13-18yr Y/N? – if too difficult to obtain the other information) Pregnancy exclusion (Y/N)

  15. Women’s ScorecardResults 73 studies identified 14 excluded 8 studies only infants and children 5 studies only women 1 study only men

  16. Women’s ScorecardResults Of the 59 remaining studies, data available so far for 29 Number of participants in 29 studies n=18,620 Number of participants per study ( median 600, IQR: 249-757) 37.9% woman participants (7060/18,620) ( range 5.9-79.2%)

  17. Score Card Results Enrollment of adolescents ( age 13-19) Per protocol: 8/59 studies One protocol adolescent only Pregnancy exclusion 49/50

  18. Score Card Results • Location of studies ( n=57) • 23 studies in high income countries only • 15 in both high and low and middle income countries • 19 in low and middle income countries only

  19. Score Card Results • Sponsor • 22 public only • 33 private only • 4 cosponsor public and private

  20. Score Card Results • Participation by women • High income (19%) vs low/middle income countries (59%), p<.001 • Public (41%) vs private (28%) sponsored studies, p<.001 vs cosponsored (70%)

  21. Limitations of Score Card Data Incomplete so far- biases in obtaining data

  22. Women’s Scorecard Next steps Continue with current score card Multivariate analysis to assess predicators of woman participants Develop similar score cards for experienced and management studies Perform of meta-analysis of the naïve trials by sex

  23. Sex is Important We need MORE POWER for women to fight this epidemic!

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