Transcript 200806_hankins_en.ppt

‘Women and clinical trials: where have we
been and where are we going?
by
Catherine Hankins
Chief Scientific Adviser to UNAIDS
Geneva, Switzerland
Hankins
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
December Meeting Cosponsors
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
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
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
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
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
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
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
Making HIV trials work for women and adolescent girls:
Action Plan
1
Support structure developed
2 Adequate representation of women in HIV trials ensured
3 Sexual and reproductive health package integrated into HIV research
4 Adolescent participation in safety and efficacy trials initiated
5 Social science perspectives integrated
6 Research agenda actions initiated
ORANGE for completed
YELLOW for active and top priority
PINK for to follow-up re status
BLUE for highly feasible & to follow-up or consider involving ourselves
GREEN for medium term (active by end of year)
WHITE for long term (ongoing)
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
Working Mechanisms
• Steering Committee:
UNAIDS, Global Coalition on Women and AIDS,
International Centre for Research on Women, and
Tibotec
• Current Working Groups:
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Score card
Sexual and reproductive health
‘Biomedical editors’
Good clinical practice
• Secretariat:
Staff in the Office of the Chief Scientific Adviser at
UNAIDS
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
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
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
http://www.cihr-irsc.gc.ca/e/32019.html
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
CONSORT Statement 2001 - Checklist
Items to include when reporting a randomized trial
PAPER SECTION
And topic
TITLE & ABSTRACT
Item
INTRODUCTION
Background
METHODS
Participants
Interventions
2
Objectives
Outcomes
5
6
Sample size
7
Randomization -Sequence generation
Randomization -Allocation
concealment
Randomization -Implementation
Blinding (masking)
8
1
3
4
9
10
11
Statistical methods
12
RESULTS
13
Participant flow
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Recruitment
Baseline data
Numbers analyzed
14
15
16
Outcomes and
estimation
17
Ancillary analyses
18
Adverse events
19
DISCUSSION
Interpretation
20
Generalizability
Overall evidence
21
22
Descriptor
Reported on
Page #
How participants were allocated to interventions (e.g., "random
allocation", "randomized", or "randomly assigned").
Scientific background and explanation of rationale.
Eligibility criteria for participants and the settings and locations
where the data were collected.
Precise details of the interventions intended for each group and
how and when they were actually administered.
Specific objectives and hypotheses.
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).
How sample size was determined and, when applicable,
explanation of any interim analyses and stopping rules.
Method used to generate the random allocation sequence,
including details of any restrictions (e.g., blocking, stratification)
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.
Who generated the allocation sequence, who enrolled
participants, and who assigned participants to their groups.
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 used to compare groups for primary
outcome(s); Methods for additional analyses, such as subgroup
analyses and adjusted analyses.
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.
Dates defining the periods of recruitment and follow-up.
Baseline demographic and clinical characteristics of each group.
Number of participants (denominator) in each group included in
each analysis and whether the analysis was by "intention-totreat". State the results in absolute numbers when feasible (e.g.,
10/20, not 50%).
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).
Address multiplicity by reporting any other analyses performed,
including subgroup analyses and adjusted analyses, indicating
those pre-specified and those exploratory.
All important adverse events or side effects in each intervention
group.
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 (external validity) of the trial findings.
General interpretation of the results in the context of current
evidence.
www.consort-statement.org
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
Sex/Gender In Clinical Trial Manuscript Submissions
(presented by Richard Horton to the International Medical Journal Editors
annual meeting June 2008)
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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?
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
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
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
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)
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
[email protected]
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS
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!
Mexico
Aug 6/08
Women and clinical trials: Where have we been and where are we going?
Hankins
UNAIDS