Ethical considerations in handling HIV prevention research protocols Brandon Brown Director of GHREAT UC Irvine Program in Public Health Irvine, CA USA 1
Discussion Points Issues in engaging participants in HIV 1. prevention research Historic events and challenges � Mistrust and coercion � Considerations in managing multisite HIV 2. prevention research protocols Gold standard treatment � incentives � 2
Engaging participants-barriers � All heard-Historic events � Nazi experiments-no consent World War II-prisoners � � Trovan Trial-no consent Epidemic of meningitis 1996 � Standard drug ceftriaxone for treatment � Pfizer tested a drug Trovan on 200 children � � Tuskegee study-withholding information (www.hopkinsmedicine.org) 3
Engaging Participants-Mistrust and Benefits in HIV prevention research � Previous HIV vaccine studies did not work � ‘you are just testing on me’ � Experience-researchers taking advantage � Collect data and take away � Question of sustainability and impact � Tested here, but not available here � 10-20 years for item to reach LMIC after approval � PrEP (iPrEx) tested in Peru, not there � HPV vaccine 4
Recruiting Participants-free choice CIOMS Guideline 7 � Council for International Organizations of. Medical Sciences � “Payment in money or in kind to research subjects should not be so large as to persuade them to take undue risks or volunteer against their better judgment. Payments or rewards that undermine a person’s capacity to exercise free choice invalidate consent.” 5
Challenges conducting trials-one country � Growing sample size of HIV prevention research protocols � efficacious treatments and prevention activities � HIV testing, microbicides, PrEP, PEP, prevention with positives, circumcision, new condoms, needle exchange, counseling and testing, MTC prevention � Limits on what can be used as a control group vs. what can be used as an intervention in a RCT 6
Considerations in managing a multisite HIV prevention research protocol � Gold standard for comparison � Intervention arm at one site is standard of care in another � Gold standard not available � Research protocol including PrEP uptake in USA and Nigeria � PrEP is approved and provided for the site in USA � Not available in Nigeria or part of guidelines � Demonstration project here may be necessary 7
Considerations in multisite study cont. � What happens when you don’t meet your efficacy goal? � Intervention deemed ineffective Even with proof of some efficacy � � Conflicts of interest � Multiple players with multiple conflicts sponsor, investigators, community advisory board, study site, � study team, IRBs � Site may need study to keep afloat � In debt to sponsor � How are you going to pay participants � Different amounts in different places? What’s fair? � 8
The issue � Incentives often necessary to obtain study participants and offset lost expenses � may jeopardize voluntary participation � Economic pressure � Non-monetary goods/services otherwise unavailable � Medical care � Little work on incentives � No parameters/rules/guidelines exist � When, how much, what kind to give?
US Policies and Procedures on Incentives � Dickert and Grady 1999 ‘Price of a research subject’ � Ethical issues on payment remain unresolved The amount may be too high and an undue inducement � � Dickert et al.2002 ‘Paying research subjects’ � 20% of groups knew what % of their studies paid participants. � Grady et al. 2005 ‘Analysis of US Practices’ � 467 clinical studies with range of payment $5-$2000 Unexplained variation across similar studies � Variation in same study at different sites � Incentive amounts are haphazard
Global policies � Where are they? � Very difficult to collect incentive info from intl. sites � Most don’t appear on www.clinicaltrials.gov � Little work done around the world and in marginalized groups � No international classifications of incentives � Is some consistency needed on payment in studies by country, type of study, risk? � South Africa unofficial guidelines on payment per visit � 150 Rand per trial visit=15 US Dollars Citation: South African Medicines Control Council �
HIV Prevention Research Incentives COUNTRY INTERVENTION INCENTIVE(S) Tanzania TESTING HIV blood test & counseling USA EDUCATION $20 for the first interview and HIV test & for the follow-up interview Kenya & Uganda PRE-EXPOSURE DRUG(S) 500-1000 (Kenyan) or 15,000-30,000 (Ugandan) shillings per visit & tea/soda/snacks* Chili EDUCATION 2,000 Chilean peseos ($5 US) each questionnaire for travel & refreshments Liberia EDUCATION $2 US per survey, $8 US total Uganda CIRCUMCISION/TESTING HIV testing* USA EDUCATION $50 Gift card for first session & $25 cash for the follow-up survey Uganda VOCATIONAL TRAINING Vocational training with local artisans in hairdressing, catering, tailoring etc.* USA COUPLE-BASED EDUCATION Monetary compensation for baseline & each follow-up assessment. Malawi WEANING 600 MK ($4 US) for transport & 1 kilogram fortified corn-soya Tajikistan EDUCATION A total of $20 for all three surveys. Japan EDUCATION Individual counseling sessions. USA EDUCATION After completion of each session, $25 was given for any expenses incurred. Bahamas PARENTAL EDUCATION No incentives were given for participation in the intervention.* USA PRE-EXPOSURE DRUG(S) Study medication, HIV test, counseling, condoms, & management of infections. USA PEER EDUCATION Index received $10 for each RNM who enrolled & $30 for baseline visit. India TESTING/EDUCATION Refreshments. South Africa MICROBICIDE None listed. USA & Puerto Rico PARENT EDUCATION Sites were compensated $5,000 & could determine what incentives to offer. Kazakhstan COUPLE-BASED EDUCATION Goods equal to US$1, US$5, & US$7 for screening, assessment, & intervention. Armenia EDUCATION $5 for each recruit, $20 for participation, & physician/attorney services. USA FEMALE CONDOM $5 for screening, $30 for baseline, & $15 for each follow-up assessment. USA EDUCATION $20 for the baseline, $25 for the 3-month, & $30 for the 6-month follow-up. Zimbabwe PAYMENT Food, school fees & supplies, uniforms & helpers received $15 US/term. Trinidad & Tobago EDUCATION TT $500/US$83 for intervention families & controls received TT $200/US$35 Bahamas CONDOM USE Monetary compensation for answering questionnaires.* USA CONDOM PROMOTION $10 GC/baseline, $5 GC/1-month, $5 bonus, $10 GC/follow-up & $5 bonus Range $0 to $83 per visit 12
Practice in Global Context � HIV study incentives usually include more than cash money � Gifts, services, food, transportation, medicine � Attention for basic medical needs addressed in studies may not be available elsewhere � Undue inducement may play a bigger role � Lack of resources � Incentives may overshadow perceptions of risk and doubts about study participation
Ex: 3 pharmaceutical studies in Peru Study 1 Study 2 Study 3 Type of clinical trial Vaccine treatment Vaccine Incentives i. money i. none i. $7 per visit i. none ii. gifts ii. Watch, ii. birthday present, watch, ii. nominal gifts iii. Health care makeup, purse, perfume, makeup, purse, iii. Genital wart wallet wallet, hair dryer, lunches removal, HIV testing, iii. Birth control, iii. Birth control, GW anal Pap smear, genital wart syndromic treatment removal, condoms and removal, lubricants, STD treatment condoms and for participant and partner, lubricants, HIV free medical attention for testing participants, children, and partners, Pap smear, HIV testing 14
Incentives Solution Ethics committee receives a research protocol 1. investigator proposed incentives in the study � look at what incentives have already been 2. approved in similar studies Development of an incentive database � in the same region, country, population, disease, etc. � Revisit if these are justified 3. Make suggestions and develop incentive 4. parameters for reference in future studies Parameters=Reasonable or existing limits � suggested incentives can published online for different types � of studies for PIs and IRBs
What should be involved in deciding Incentive Amounts Incentives Money Gifts Health services Other Brown 2013, IRB Features of Index Protocol Features of Research Setting Condition under study Study population Locale Risks Daily Income Prospect of direct benefit Major Causes of disease Recruitment strategies Availability of health services 16
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