hankins unaids mexico aug 6/08 women and clinical trials: where have we been and where are we going?...

HankinsUNAIDS

MexicoAug 6/08 Women and clinical trials: Where have we been and where are we

going?

‘Women and clinical trials: where have we been and where are we

going?by

Catherine HankinsChief Scientific Adviser to UNAIDS

Geneva, Switzerland

Hankins

HankinsUNAIDS


going?

December Meeting Cosponsors

HankinsUNAIDS


going?

Definitions• Sex:

– biological differences between males and females.

– typically considered to be a binary category

• Gender:– a socially-constructed notion of what is feminine

and what is masculine– socially defined differences between men and

women– Gender is a continuous category: a person can

be more or less feminine or masculine

HankinsUNAIDS


going?

Meeting Agenda• Historical evolution of women’s participation in

clinical trials • State of knowledge on sex differences in

biomarkers, pharmacokinetics, and drug interactions

• Interaction between reproductive health and HIV

• Gender issues in new prevention technologies and treatment paradigms

• Barriers, challenges and opportunities for research for women and adolescent girls

• Outcomes: – Policy and programmatic recommendations– Research agenda– Advocacy plan

HankinsUNAIDS


going?

Recommendations

• Establish a “new norm” that it is not acceptable for research on critical health and drug interventions to exclude women, or to include them in token numbers.

• Build mechanisms of accountability within regulatory frameworks and other standard setting bodies to require trials to gather, analyze, and report sex disaggregated data.

• Ensure that women are adequately represented in all HIV-related trials that may affect them – basic science, prevention, treatment, structural – and that they are enrolled and retained in sufficient numbers to allow for adequate power to draw conclusions based on subgroup analyses

HankinsUNAIDS


going?

Making HIV trials work for women and adolescent girls: Action Plan

1 Support structure developed

2 Adequate representation of women in HI V trials ensured

3 Sexual and reproductive health package integrated into HI V research

4 Adolescent participation in safety and effi cacy trials initiated

5 Social science perspectives integrated

6 Research agenda actions initiated

ORANGE for completed

YELLOW for active and top priority

PI NK for to f ollow-up re status

BLUE for highly f easible & to f ollow-up or consider involving ourselves

GREEN for medium term (active by end of year)

WHI TE for long term (ongoing)

HankinsUNAIDS


going?

Working Mechanisms

• Steering Committee: UNAIDS, Global Coalition on Women and AIDS, International Centre for Research on Women, and Tibotec

• Current Working Groups:– Score card– Sexual and reproductive health– ‘Biomedical editors’– Good clinical practice

• Secretariat:Staff in the Office of the Chief Scientific Adviser at UNAIDS

HankinsUNAIDS


going?

Biomedical editors working group

• Assessed public research sponsors funding requirements for research proposals (NIH, CIHR, MRC, ANRS, etc.)

• Contacted Consort Group to see if the checklist for reporting on clinical trials could be modified to add a sex- and gender-related components

• Proposed the addition of questions to the International Medical Journal Editors annual meeting

HankinsUNAIDS


going?

http://www.cihr-irsc.gc.ca/e/32019.html

HankinsUNAIDS


going?

CONSORT Statement 2001 - Checklist Items to include when reporting a randomized trial

PAPER SECTION

And topic Item Descriptor Reported on

Page # TITLE & ABSTRACT 1 How participants were allocated to interventions (e.g., "random

allocation", "randomized", or "randomly assigned").

INTRODUCTION Background

2 Scientific background and explanation of rationale.

METHODS Participants

3 Eligibility criteria for participants and the settings and locations where the data were collected.

Interventions 4 Precise details of the interventions intended for each group and how and when they were actually administered.

Objectives 5 Specific objectives and hypotheses. Outcomes 6 Clearly defined primary and secondary outcome measures and,

when applicable, any methods used to enhance the quality of measurements (e.g., multiple observations, training of assessors).

Sample size 7 How sample size was determined and, when applicable, explanation of any interim analyses and stopping rules.

Randomization -- Sequence generation

8 Method used to generate the random allocation sequence, including details of any restrictions (e.g., blocking, stratification)

Randomization -- Allocation

concealment

9 Method used to implement the random allocation sequence (e.g., numbered containers or central telephone), clarifying whether the sequence was concealed until interventions were assigned.

Randomization -- Implementation

10 Who generated the allocation sequence, who enrolled participants, and who assigned participants to their groups.

Blinding (masking) 11 Whether or not participants, those administering the interventions, and those assessing the outcomes were blinded to group assignment. If done, how the success of blinding was evaluated.

Statistical methods 12 Statistical methods used to compare groups for primary outcome(s); Methods for additional analyses, such as subgroup analyses and adjusted analyses.

RESULTS

Participant flow

13 Flow of participants through each stage (a diagram is strongly recommended). Specifically, for each group report the numbers of participants randomly assigned, receiving intended treatment, completing the study protocol, and analyzed for the primary outcome. Describe protocol deviations from study as planned, together with reasons.

Recruitment 14 Dates defining the periods of recruitment and follow-up. Baseline data 15 Baseline demographic and clinical characteristics of each group.

Numbers analyzed 16 Number of participants (denominator) in each group included in each analysis and whether the analysis was by "intention-to-treat". State the results in absolute numbers when feasible (e.g., 10/20, not 50%).

Outcomes and estimation

17 For each primary and secondary outcome, a summary of results for each group, and the estimated effect size and its precision (e.g., 95% confidence interval).

Ancillary analyses 18 Address multiplicity by reporting any other analyses performed, including subgroup analyses and adjusted analyses, indicating those pre-specified and those exploratory.

Adverse events 19 All important adverse events or side effects in each intervention group.

DISCUSSION Interpretation

20 Interpretation of the results, taking into account study hypotheses, sources of potential bias or imprecision and the dangers associated with multiplicity of analyses and outcomes.

Generalizability 21 Generalizability (external validity) of the trial findings. Overall evidence 22 General interpretation of the results in the context of current

evidence.

www.consort-statement.org

HankinsUNAIDS


going?

Sex/Gender In Clinical Trial Manuscript Submissions

(presented by Richard Horton to the International Medical Journal Editors annual meeting June 2008)

Five key questions to assist medical journal editors and/or peer reviewers in assessing manuscripts that report on clinical trial outcomes.

• Where the health priority studied affects both men and women, have both women and men subjects been included in the trial and if so, have they been included in sufficient numbers so as to be able to assess outcomes in each and differences between them?

• Have women subjects been excluded and, if so, for what reasons (i.e. cost, reproductive considerations, etc.)?

• Have the data been disaggregated by sex and analyzed by sex and gender?

• Were anatomical and physiological differences between men and women (i.e. height, weight, body fat-to-muscle ratios, cell counts, hormonal cycles, etc.) as well other variables (socio-economic, education, access to care, etc.) taken into consideration in the presentation of data and/or analysis of the results?

• If a statistically significant difference was found between men and women in the effects of the studied intervention, are the implications, if any, for clinical and/or public health discussed?

HankinsUNAIDS


going?

Good Clinical Practice Working Group

• Reviewed the International Council on Harmonization (ICH) Good Clinical Practice (GCP) guidelines for content on women, adolescent girls, and community engagement, finding no mention of sex or gender

• Requested consideration for endorsement of the UNAIDS/AVAC Good participatory practice (GPP) guidelines

• Exploring the possibility of harmonisation based on the 1993 NIH policy, enacted by public law, explicitly stating that women must be included in any clinical studies conducted or supported by NIH

HankinsUNAIDS


going?

HankinsUNAIDS


going?

Guidance on conduct of HIV biomedical HIV prevention trials

• UNAIDS has produced two products to guide scientifically rigorous and strong ethical conduct of both ongoing and future biomedical HIV prevention trials, both of which address women and adolescent girls

• Good Participatory Practice Guidelines (with AVAC) and Ethical Considerations (with WHO)

HankinsUNAIDS


going?

HankinsUNAIDS


going?

[email protected]

HankinsUNAIDS


going?

Thanks to:• Tania Lemay, Elizabeth McGrory, Nicolai Lohse• Participants in the consultation, Steering Group

and Working Group members• Women in HIV prevention and therapeutic trials

everywhere• Far-sighted medical editors, regulatory bodies,

and research agencies setting standards• All who are participating in creating new norms

on women and clinical trials, including you!

hankins unaids mexico aug 6/08 women and clinical trials: where have we been and where are we going?...

Documents