Transcript Standard of Care HIV/AIDS Research

Capacity Building Workshop on Ethics in HIV/AIDS Research
Pune 15 Sep 2011
Standard of Care
HIV/AIDS Research
Sheela Godbole MD
National AIDS Research Institute (ICMR), Pune
Learning Objectives: SOC

Ethical Principles underlying Standard of Care

Defining SOC: what? who? When

Identify the issues related standard of care in
bio-medical research

Discuss issues specific to HIV/AIDS with
examples

Standards of Care and Trial Designs
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A Non -negotiable Principle
Underlying Clinical Research
The health and well-being of participants must
be the primary concerns during research and
these should prevail over any other concerns,
including the interests of science
Best practices -UNAIDS 2002
Respect for the individual and the
community should be at the core of
research in developing countries

Participants must be provided with a
context of care that

 Fully addresses their dignity
 Responds to their physical and psycho-social
health needs.
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Standard of Care – Principles to Consider
Principles of
 Beneficence (maximum benefit and minimal harm)
 Reciprocity (Return benefit)
 Justice as equity (treat like cases alike)
Standard of Care – Points to Consider
What is Best Available world over?
What is Recommended as best (locally)
What is Best Accessible
(locally)
What is available for Public access locally
DEFINING SOC
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Standard of Care
“A suitable SOC can only be defined in
consultation with those who work in country
and…
Should reflect care that can be effectively
delivered during research and on
sustainable basis in country ”
Nuffield Council, 2002.
Standard of Care – Points to Consider
 The Best Treatment available :
(ideal is to provide best proven treatment)
Supported by Principle of beneficence, reciprocity, justice as equity
 Highest attainable treatment in the country of
research (minimum standard)
Supported by principle of beneficence
 Level of care provided in the public health
system of the country of research
Supported by principle of Justice as equity
Standard of Care
•
‘Best available care’ has never been welldefined in medicine.
•
SOC - Different in different parts of the
world according to:
◦
Provider knowledge, comfort, training and belief
◦
Local resources and context
◦
Ability of the patient to pay
SOC Varies with
Context & Category of Trial participants
•
Healthy adult men and women [Vaccine,
microbicides]
•
Negative partners of HIV infected
persons [ART]
•
•
Those who may develop breakthrough HIV infection
HIV infected individuals or PLHA [ART]
SOC Varies with Region:
Inequities exist not just between countries, but
also within them
Variations among ‘standard of care’
 Differential access
to antiretrovirals,
basic drugs for opportunistic infections and pain relief
Technology (CD4,VL, RT; CT Scans, )
Infrastructure
 trained health-care personnel, including counselors for
psychosocial care
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SOC Varies with Region:

Can be the best available care that is practicable
under local circumstances

The community must be involved in determining
and agreeing on the standard of care to be
employed

Researchers must include this issue in the
consultation with the community during the
design and implementation of the research
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Role of Sponsors for Providing Access
to Care

Capacity Building
 Developing
 Transfer
Standards
of Technology
 Post Trial Access
 Low
Cost access to Trial Product post
approval to the community—
vaccine/microbicide
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Who can help determine SOC?
Research
Team/Medical
Community/
Scientists
CABS/FBO/
Womens
Groups/Policy
Makers/Media
Volunteers
Key National/
Regional/ Global
Stakeholders
Ethics
Committee
Study Sponsors
What helps to define SOC?
•
Accepted Knowledge
•
Existing Evidence
•
Compliance Expected
•
Personnel Responsible
•
Use of Methodologies-Specific, measurable and Time
Bound
•
◦
Self Assessment
◦
External Assessment
Desirable expectations - Evidence needed to validate
meeting of expectations
◦
Expectations should be resource neutral
SOC and Research Design
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SOC and Research Design
Decisions on SOC and Access may be decided
on
 (1) the objective of the study

(2) the level and duration of contact with
the study participants; and

(3) an evaluation of the availability and
accessibility of medical care in the research
area
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SOC and Research Design

Surveillance and other similar studies that benefit /guide
public health interventions may be judged by a different
yardstick

Consider background availability of locally care and
standards

SOC can affect research design:
◦ Placebo/ control,
◦ advances in care or results from other studies may stop trial or
change randomization
◦ Change protocol specified treatment criteria– mid course
corrections
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Issues to ponder..1
If the prevailing standard of care is noticeably higher in a developed
country (from where the investigator and/or sponsor come from) than
in a developing country (where the research will be carried out):
◦ Is it ethical to provide the highest standard of care available
anywhere in the world to the control arm knowing that others in the
country with the same medical condition are not able to access that
care?
◦ Might care at such a high level amount to an unfair inducement to
participate in the research?
◦ Is it ethically preferable to provide – or not to provide – the highest
standard of care to participants in the trial if there is no commitment
(on the part of the research sponsor or the localhealth authorities) to
continue to provide that level of care after the trial is finished?
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Issues to ponder..2

How is the “highest standard of care” defined?
Compare these circumstances in which the treatment deemed
best in wealthy countries:
 Is simply not feasible in a developing country context
 Has not yet been approved for sale
 Is available in the developing country but only at high
prices, or to a small elite, and though it could in
practice be provided to all who need it, the cost (in
money and/or in medical resources) would make this an
unwise use of resources
 Has not be designated as the treatment of choice
by the local ministry of health
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A CASE STUDY: HPTN 052
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HPTN 052: A Phase III Randomized
Controlled Trial
A Multi centric Study among HIV discordant couples to
 To determine if ART reduces HIV-1 transmission,
◦ magnitude?
◦ durability of benefit?
 To determine if ART used “earlier” to reduce HIV-1 transmission
provides
◦ personal health benefit(s)?
HPTN 052 Study Design
Stable, healthy, serodiscordant couples, sexually
active
CD4 count: 350 to 550 cells/mm3
Randomization
Immediate ART
CD4 350-550
Delayed ART
CD4 <250
Primary Transmission Endpoint
Virologically-linked transmission events
Primary Clinical Endpoint
WHO stage 4 clinical events, pulmonary tuberculosis, severe bacterial
infection and/or death
HPTN 052 Study Design…….
All participants in both groups received:




counseling on safe sex practices,
free condoms,
treatment for sexually transmitted infections, frequent HIV
testing and evaluation
treatment for any complications related to HIV infection
Genital samples were collected
Blood samples from index and partner were collected at the
time of sero-conversion for viral studies
Visits: 15 days x1, Monthly x 2, and Quarterly…..
Can we identify SOC Issues in this trial?
Other Ethical Issues?
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Issues vary with Participant Type
Screened
out
Uninfected
Partner
Couples
Infected
Partner
Sero
Converted
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Issues that needed addressal
Negative Partner
Couples
•
• Disclosure to Partner,
Children
Seroconvert care
• Counseling for Prevention
• Couples Counseling
• Clinical Care
• HIV risk reduction
• Family planning and
Contraception
• Marital Discords
• Exclude Abstinent Couples
• Visits
Infected Partner:
•
Care for HIV
•
ART Access Post Trial
•
ART Access in Delayed Arm
When?
•
Prevention of TB and OI
•Other:
•Continuity of care,
Capacity building, Research related harms,
•Post-Exposure prophylaxis for study staff,
Ancillary care, Social impact
SOC Situations
 Access to Care and treatment : Delayed arm
 Post Study Access: Patients on ART
 (Before Free ART and After Free ART)
 Access to Prevention
 TB in Positives
 HIV in negatives
 Access to Care for HIV disease
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Challenges
Challenge
Reason
Universal vs. best local available care
Similar standards should be maintained
by the external sponsoring agency.
Higher SOC than otherwise available
may be seen as an undue inducement
to participate in trial
Issue of equity in multicentric trials
Treatment of research related injury- timeframe
Treatment of HIV infection is expensive
and life long medications must be
taken.
Decide the correct balance between
appropriate re-imbursement and undue
inducement
Community participation
Supportive environment, ownership,
address social stigma, facilitate effective
recruitment and retention
Pre-trial agreements
Other things to consider
•
Costs for care and treatment
•
Costs for travel
◦
Out of schedule visits
•
Clinical trial drop-outs
•
Participants terminated from the study
•
Women becoming pregnant during the trial
SOC Practiced
 Comprehensive Care
◦
Study-related care- Minimum Standards/highest attainable treatment
in India
◦
Provision of other non study-related care (primary health care)
◦
Participants who became HIV-infected during the course of the trial
HIV/AIDS care, support and treatment services offered
◦
HIV/AIDS care provided as a continuum (from home, community,
peripheral unit to hospital, including follow up and back referral)

National definitions and guidelines followed

Inter-linkages maintained by researchers within service delivery
points.
SOC Practiced

Established effective mechanisms
◦
Defined agencies and mechanisms
◦
Referral system and access provided for HIV care, support,
investigation and treatment (inpatient and outpatient) for
those found HIV-infected at screening during trials and
feasibility studies
◦
Initiated from the asymptomatic phase onwards as clinically
indicated
◦
Maintained meticulous medical records of treated
participants.
SOC Practiced
•
Well-defined Standard Operative Procedures [SOPs] for care and
treatment developed
•
Clinical trial participants given information in the consent forms,
visual aids, study brochures in a transparent manner( continuous
ongoing process during the study)
•
Strengthened Existing Infrastructure (trial center dependent)
•
Quality Assurance and Quality improvement for service delivery
•
Laboratory Management
Complex Ethical Perspectives in
HIV Research

Complex Dimensions
◦
Research participants that are infected

Health needs

Social Impact
◦
Scientific Output Influences

Design of Future trials

Access to Successful Products researched
Some Guidance
•
ICH-GCP
•
US Federal Policy for Protection of Human Subjects
•
Declaration of Helsinki
•
AVAC Guidelines
•
Ethical Considerations in Biomedical HIV Prevention Trials
2007 – UNAIDS/WHO
•
Good Participatory Practices for Biomedical HIV Prevention
Trials
•
National Regulations Guidelines