Standards of Prevention:    Ethics in the Era   of ART Prophylaxis               Jonathan Jay, JD MAO’Neill Institute for ...
IntroductionWhat should researchers do to reduce HIV risk among study participants in prevention trials?“Standards of prev...
Biomedical HIV prevention methodsFor sexual transmission• In widespread clinical practice:    –   Male/female condoms    –...
ART chemoprophylaxis• Microbicide (vaginal TDF 1% gel)  – CAPRISA 004: 39% efficacy• PrEP (oral tenofovir/Truvada)   – iPr...
Ongoing/future research• Expand on PrEP, microbicide data   – Confirmatory studies   – Feasibility/cost-effectiveness• Opt...
HIV Prevention Trial Design• Randomized controlled trial = gold                                                    STUDY P...
STUDY PARTICIPANTS           Double-blind RCT           for           biomedical HIV       NEW           prevention       ...
Incidence and sample size
Hypothetical HIV Vaccine TrialSource: NIH Combination Prevention Workshop, 2010 (unpublished)
Current/future trialsHVTN 505:• Combo vaccine vs. placebo  – 2200 MSM in U.S.MTN-020:• Dapivirine ring vs. placebo  – 4000...
Methods• Analyzed UNAIDS/WHO guidance• Analyzed key international ethics documents  – Declaration of Helsinki (WMA)  – CIO...
Approaches to standards of prevention1. Maximum benefit to participants  – Key ethical issues         •      Beneficence: ...
Approaches to standards of prevention2. Match local clinical practice  – Key ethical issues     •   Public health goals   ...
UNAIDS/WHO approach• Most influential guidance on standards of  prevention• Aligned with “maximum benefits” approach  – Pa...
UNAIDS/WHO and ARV prophylaxis“All state of the art” is problematic  1. Methodological/scientific issues  2. When to inclu...
Intermediate conclusions• Both sides are right—must understand principles  in light of valid concerns• UNAIDS/WHO should b...
Threshold Approach• Set threshold for presumptive inclusion• Provide analysis of how modality might be  withheld 1.     Me...
Clinically Reasonable• Background package should be clinically  reasonable      – Efficacy, safety; behavioral; acceptabil...
Three-step frameworkStep 1: when validated for clinical use, should bepresumptively providedStep 2: is withholding the mod...
AcknowledgmentsGlenda Gray       Contact:Ken Mayer         jsj@law.georgetown.eduIan McGowanLiza DawsonCollin O’NeilHannah...
Upcoming SlideShare
Loading in …5
×

Standards of Prevention: Ethics in the Era of ART Prophylaxis

531
-1

Published on

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
531
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
3
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Standards of Prevention: Ethics in the Era of ART Prophylaxis

  1. 1. Standards of Prevention: Ethics in the Era of ART Prophylaxis Jonathan Jay, JD MAO’Neill Institute for National and Global Health Law Georgetown University National HIV Prevention Conference August 16, 2011
  2. 2. IntroductionWhat should researchers do to reduce HIV risk among study participants in prevention trials?“Standards of prevention”Answering this question: more difficult in the age of safe, effective ARV-based prevention (PrEP, microbicide)
  3. 3. Biomedical HIV prevention methodsFor sexual transmission• In widespread clinical practice: – Male/female condoms – STI testing and treatment – PEP – Male circumcision – Treatment as prevention• Proof of concept: – PrEP – Microbicide
  4. 4. ART chemoprophylaxis• Microbicide (vaginal TDF 1% gel) – CAPRISA 004: 39% efficacy• PrEP (oral tenofovir/Truvada) – iPrEx: 42% efficacy among MSM – FEM-PrEP: stopped for futility (women) – Partners: 62/73% among men and women – TDF2: 62% among men and women
  5. 5. Ongoing/future research• Expand on PrEP, microbicide data – Confirmatory studies – Feasibility/cost-effectiveness• Optimizing combination strategies• New modalities – Vaccine – Rectal microbicide – Additional ARV options
  6. 6. HIV Prevention Trial Design• Randomized controlled trial = gold STUDY PARTICIPANTS standard Random assignment NEW• Placebo-controlled RCT (e.g. iPrEx, PLACEBO MODALITY CAPRISA 004) – Randomization New infections – New infections counted – Compare study groups
  7. 7. STUDY PARTICIPANTS Double-blind RCT for biomedical HIV NEW prevention PLACEBO MODALITYUNAIDS/WHO 2007: CONDOM ACCESS“appropriatecounselingand access RISK REDUCTION COUNSELINGto all state Backgroundof the art packageHIV risk STI TEST & TREATreductionmethods”must be PrEP/MICROBICIDE?provided
  8. 8. Incidence and sample size
  9. 9. Hypothetical HIV Vaccine TrialSource: NIH Combination Prevention Workshop, 2010 (unpublished)
  10. 10. Current/future trialsHVTN 505:• Combo vaccine vs. placebo – 2200 MSM in U.S.MTN-020:• Dapivirine ring vs. placebo – 4000 women in Southern Africa
  11. 11. Methods• Analyzed UNAIDS/WHO guidance• Analyzed key international ethics documents – Declaration of Helsinki (WMA) – CIOMS Ethics Guidance – Belmont Report (USA)• Literature review• Consultations with HIV prevention researchers
  12. 12. Approaches to standards of prevention1. Maximum benefit to participants – Key ethical issues • Beneficence: – Maximize benefits, minimize risks to subjectsa – Do not withhold current, proven interventionb • Non-exploitation – Avoid taking advantage of subjects a: Belmont Report (U.S. Presidential Commission) b: Declaration of Helsinki (World Medical Assn)
  13. 13. Approaches to standards of prevention2. Match local clinical practice – Key ethical issues • Public health goals – Trials which are speedier, less expensive, less complex • Non-maleficence – Subjects are no worse off than outside study • Sustainability – May be impossible to guarantee long-term access to some modalities
  14. 14. UNAIDS/WHO approach• Most influential guidance on standards of prevention• Aligned with “maximum benefits” approach – Package must include “all state of the art” interventions UNAIDS/WHO Ethical Considerations in Biomedical HIV Prevention Trials, 2007
  15. 15. UNAIDS/WHO and ARV prophylaxis“All state of the art” is problematic 1. Methodological/scientific issues 2. When to include • Evidence continuously emerging • Too late/too early both ethically problematic 3. Appropriate combination approach • Ensuring benefit • Adequacy as baseline
  16. 16. Intermediate conclusions• Both sides are right—must understand principles in light of valid concerns• UNAIDS/WHO should be updated/revised• A new approach would better fit the challenges posed by ARV chemoprophylaxis – Jay, Gray, Mayer, McGowan (forthcoming)
  17. 17. Threshold Approach• Set threshold for presumptive inclusion• Provide analysis of how modality might be withheld 1. Methodological/scientific issues 2. When to include • Evidence continuously emerging • Too late/too early both ethically problematic 3. Appropriate combination approach • Ensuring benefit • Adequacy as baseline
  18. 18. Clinically Reasonable• Background package should be clinically reasonable – Efficacy, safety; behavioral; acceptability 1. Methodological/scientific issues 2. When to include • Evidence continuously emerging • Too late/too early both ethically problematic 3. Appropriate combination approach • Ensuring benefit • Adequacy as baseline
  19. 19. Three-step frameworkStep 1: when validated for clinical use, should bepresumptively providedStep 2: is withholding the modality methodologicallynecessary?Step 3: does the study address a compelling publichealth need?
  20. 20. AcknowledgmentsGlenda Gray Contact:Ken Mayer jsj@law.georgetown.eduIan McGowanLiza DawsonCollin O’NeilHannah BurrisKelli GarciaJackie Huh
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×