Transcript Mapping standards of care in trials of microbicides or the diaphragm

Mapping standards of care in trials
of microbicides or the diaphragm
Global Campaign for Microbicides
Katharine Shapiro
Microbicides 2008
February 24-27
New Delhi, India
Thanks…
International and site
level investigators
and staff
Katie West, Lori Heise,
Sean Philpott
U.S. Agency for
International
Development
Overview
INTRODUCTION
 The Global Campaign
 Standards of care (SOC) definitions and debates
THE SOC MAPPING EXERCISE
 Goals
 Methods
 Findings
 Conclusions and recommendations
The Global Campaign for
Microbicides works to:
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Mobilize demand and investment for research
and development of new HIV prevention
technologies, especially for women
Conduct policy advocacy for development,
testing, access, and use
Ensure accountability - that as science proceeds,
public and community interests are fully protected
The evolution of standard of care
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A concept imported from medicine - what a reasonable
physician should provide in order not to be negligent
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Applied to research, especially to describe care
provided to people in control arm of a RCT
While ethics debate on SOC has been primarily about RCTs
or provision of ART to seroconverters, we use SOC here
to describe
1. the care and prevention services offered during a
clinical trial (study-related and ancillary care)
2. the care available in the local community/host country
The importance of context
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“A suitable SOC can only be defined in
consultation with those who work in
country…and should reflect SOC that can be
effectively delivered in host country during
research and on sustainable basis” Nuffield
Council, 2002.
What defines standards?
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‘Best available care’ has never been well-defined
in medicine.
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Standards of care vary within and between
developed and developing countries according to
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provider knowledge, comfort, training and belief,
local resources and context
ability of the patient to pay.
The SOC debates
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Erupted in 1997 over controversial trials of
nevirapine to prevent mother to child
transmission of HIV in developing countries
The ethics of using a placebo when a proven
regimen to prevent transmission existed in the
United States were questioned
Debate is embedded in unequal distribution of
wealth between countries sponsoring research
and those hosting it.
Ethical questions that plague HIV
prevention trials
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Is it ethically obligatory for trials to improve SOC
while conducting research?
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Whose obligation is it?
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Should trials fund ART for seroconverters?
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What is the obligation to provide care to women
found HIV+ at screening who cannot enroll?
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Are dual SOC are problem?
Dual standards of care
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Dual SOC between sponsoring and host
country
Dual SOC between sites within one multi-site
trial
Dual SOC between what the research facility
provides and what the local community can
provide
Conflicting ethics guidance
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Declaration of Helsinki: Best current standard
should be used, but a placebo can be justified in
certain specific circumstances.
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NBAC: Recommends established, effective
treatment regardless of local availability. (U.S.)
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Nuffield Council: Emphasizes current standard local
treatment. (U.K.)
Conflicting ethics guidance
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CIOMS: While care essential to the research is
obligatory; other care is “morally praiseworthy”
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UNAIDS Ethical considerations in biomedical HIV
prevention trials (2007): Participants who
seroconvert should be provided access to treatment
from among regimens internationally recognized as
optimal.
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And… prevention trials ought to contribute
constructively to development of HIV service
provision in participating countries for sustainable
provision of care and treatment after a trial.
The SOC mapping exercise
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Despite lengthy debates, information on how
researchers and sites were addressing these
issues on the ground in different countries and
contexts has been limited
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Empiric evidence from the field could inform
discussion among all stakeholders on trial ethics,
& generate ideas for future trial design
Goals of SOC mapping
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Document progress made by researchers toward
meeting ethical guidance and aspirations
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Compare context-specific challenges in provision
of care and prevention
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Describe different SOC strategies and how sites
implemented them
Methods
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Development of survey guide with input from
investigators and staff
Desk review of 7 study protocols & international
and site-level documents (SOPs, manuals)
In depth interviews with international investigators
and sponsors
Visits to a sample of 6 sites and community
clinical facilities in 4 countries
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In-depth interviews with site trial staff
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Consultation in Johannesburg, SA
Sites included
Site
Trial
Product
1. Cape Town, S.A.
2. Shoshanguve, S.A.
Population Council
Carraguard
3. Cotonou, Benin
CONRAD
Cellulose sulfate
4. Kwa Zulu Natal S.A.
5. Mwanza, Tanzania
Microbicides
Development
Program
Pro 2000Gel
6. Harare, Zimbabwe
-HIV Prevention Trials -BufferGel & Pro 2000 Gel
Network
-MIRA
-Diaphragm
*Not visited:
7. Nigeria, Ghana
Family Health
International
Savvy in Ghana
Cellulose sulfate in Nigeria
Range of issues
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HIV risk reduction
STI services
Cervical screening
Contraception
Pregnancy
Seroconverter care
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Screen-out HIV+ care
Capacity building
Ancillary care
Research related harms
Continuity of care
Findings: overview of variations study and site
Setting
 urban
 peri-urban
 rural
Study facilities
 mobile clinics in rented
rooms
 stand alone research
clinics
 within or adjoining
government clinics
Findings: overview of variations study protocol and site
Study populations
 primary health care
clients
 family planning clients
 bar and hotel workers
 sex workers
Local health services
 health infrastructure
and spending
 outside funding
Overview of variations - services
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What services provided:
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Who services were for:
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study-related care only
provision of other non study-related care (primary
health care)
participants only
partners and family members of participants; screened
out women
Where services were provided:
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on site
by referral
nature of referral mechanisms
Variations in study-related services
provided
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All studies provided a comprehensive HIV
prevention package with
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unlimited RR counseling, comprehensive STI care ,
condoms, some couples counseling offered
Most provided contraception (often added later)
Most provided female condoms, cervical cancer
screening, diagnosis and treatment
Most provided counseling and STI care for men
One provided an HIV support group
Variations in non-study related care
provided
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MDP South Africa: Ancillary care for study participants and
families - ill children, childhood immunizations, using supplies
from the adjacent DOH-run clinic
MDP Mwanza, Tanzania: no ancillary care. Study visits take
place in rented rooms where a limited mobile clinic is set up
Pop Council, South Africa: Little ancillary care.
CONRAD Benin: Complete HIV prevention and care
(including ART)to all, but no ancillary care - referral for all nonreproductive health problems.
HPTN 035 Zimbabwe:. Diagnosis and/or treatment for a
limited number of ancillary health concerns (e.g., malaria,
minor infections, etc.) provided
FHI Nigeria and Ghana: Virtually no ancillary care
Variations within specific
services
Cervical
cancer
screening
HIV Care
Cervical screening
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Incidence of vaginal & cervical lesions are secondary
safety endpoints in trials
Visual examination of vagina and cervix are required
& colposcopy of any lesions to determine if productrelated
Some sites offer Pap smears to women at
enrollment; some to women at study screening,
some don’t offer them
Cervical screening is not of much use if a system is
not in place to address continuing need for
diagnosis, treatment & follow up
Variations in cervical screening
South Africa: free national screening and treatment
program but public system overloaded (long waits,
losses to referral and f/u) --though women with
abnormal results may get more attention
 Trial participants with abnormal Paps are ensured
diagnosis & treatment including transport to referral
centers, until trial ends
 Women who are not participants get free screening
but are referred on to public system
Variations in cervical screening
Zimbabwe: limited public services
 HPTN 035 provides Paps at enrollment and
abnormalities are diagnosed, treated and followed
by study M.O.
 MIRA did not provide Paps routinely but on
participant request
Tanzania: no public services
 MDP Mwanza does not provide Paps
Benin and Nigeria: no public services
 FHI & CONRAD trials provided no screening - if
suspicious lesions found, women referred to
private doctors
Cervical cancer screening
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Trials improve care for women by raising awareness,
screening, training providers (SA - MDP & PC); by
providing new services themselves (Zimbabwe
HPTN)
Consensus recommendation: Future trials should
at a minimum provide cervical screening if some
publicly supported services exist, but where none
exist investigators should advocate for and support
initiation of services. Trials can contribute by offering
training to public sector providers in screening,
colposcopy, and low technology techniques such as
VIA where approved.
Variations in care for participants
who became HIV+
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All but 1 trial allowed women to continue in study and
receive study related care
All provided ‘assisted referrals’ to govt. HIV/AIDS
services - level of assistance varied
Some trials offered
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WHO clinical staging
baseline lab evaluations (CD4, LFTs)
1 study actually provided funds up front for ART
when needed in future
Variations in care for HIV+ women
screened out
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All studies offered extra post-test counseling and
referral;
All studies but 1 provided STI screening and/or
treatment to woman and partner;
Some provided WHO staging and CD4counts ;
One provided an HIV+ support group;
One provided the same care (incl. ART) to everyone
- screened out and seroconverting participants and
the community
All were increasingly concerned and responsive to
need for services for women screened out
Different strategies for care
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Population Council Carraguard SA - independent
research clinics, study-related care, only for participants
(except STIs); relied on referral, implemented a SOC
study
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MDP SA Pro2000 - research clinics co-located with govt.
services, benefited from PEPFAR funding secured by the
research center, directly provided PHC for women and
families
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MDP Tanzania Pro2000 - mobile clinics for high risk
mobile women - study related-care only, primarily for
participants
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MIRA diaphragm Zimbabwe - largely study-related care
only in a research only clinic; implemented SOC study
Strategies for care (2)
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HPTN 035 BufferGel & Pro2000 Zimbabwe - research
clinics on government clinic grounds; some PHC (ancillary
care) provided
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CONRAD CS Benin - complete study related and HIV/AIDS
care to all high risk women and men including ART,
regardless of study participation. Referrals for all other care,
in most cases not paid for by study. ART for seroconverters
funded before study began.
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FHI Nigeria CS and Ghana Savvy - most study visits in
health posts with limited study-related care, no ancillary care.
Some cross-cutting issues
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Fragile health systems
Sensitivity about dual SOC and ‘undue inducement’
Weak referral mechanisms
Partnerships to provide care
Location of trial sites - co-location with other facilities
vs. stand-alone research clinics or mobile clinics
Male partner involvement
Conclusion (1)
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Sites providing the most comprehensive
care allocated resources from the start,
formed working partnerships with
government, and co-located research with
public facilities.
Recommendation (1)
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Future trials should seek opportunities to colocate or partner with existing local care
facilities before a trial begins. This can
facilitate easier access to referral services for
participants, strengthen opportunities for carerelated synergies and build long-term SOC
capacity in the host community.
Conclusion (2)
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Microbicide trials provide an example of high
quality integrated SRH, HIV/AIDS and often
primary care within deprived settings that can
‘ratchet up’ SOC in communities, and help
meet ethical aspirations.
Recommendation (2)
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HIV prevention researchers, sponsors and
donors should make every effort to use
microbicide trials as an opportunity to
strengthen and improve local standards of
care and services in host communities, and
host countries where possible. The minimum
objective should be to incrementally improve
care in a sustainable fashion to reduce global
disparities in health.
Conclusion (3)
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There were no sites where community was
consulted about what SOC should be provided
until after a study had been designed and
implemented.
Recommendation (3)
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All future studies should explicitly define
standard of care that will be provided - the
broad elements of care can be described in
the protocol, while site specific elements can
be written into site standard operating
procedures. Community voices should be
sought and integrated into SOC decision
making at every stage of the trial design and
implementation.
Thank you!