Group 2: Ethical, Regulatory, &Group 2: Ethical, Regulatory, & Community Issues

D R th M kli (Ch i ) Alb t Ei t i C ll f M di iDr. Ruth Macklin (Chair), Albert Einstein College of MedicineMs. Charla Andrews, USAMC-AFRIMSMr. Kevin Fisher, AIDS Vaccine Advocacy CoalitionDr. Yupin Lawanprasert, Thai FDAMs. Patricia Morgan, USAMC-AFRIMSDr Chawetsan Namwat MOPH-ThailandDr. Chawetsan Namwat, MOPH ThailandDr. Saladin Osmanov, WHODr. Punnee Pitisuttithum, Mahidol University

S h k O h l dDr. Supachai Rerks-Ngarm, MOPH-ThailandMs. Nusara Thaitawat, USAMC-AFRIMSMr. Nimit Tienudom, AIDS-Access Foundation,

Note Taker: Ms. Liz Shoaf

The Ministry of Public Health, researchers, and sponsors have no obligation at this time to provide the RV144 vaccine regimen to the placebo group in the trial. The following reasons, taken together,

th j tifi ti f thi d tiare the justification for this recommendation.1. The level of efficacy demonstrated in the trial is too low, and the

confidence interval too, wide to warrant provision of this vaccine regimen to the placebo control group.

2. The roadmap established during the trial set the level of efficacy at 50%, which is higher than that demonstrated in the trial. This determination provided a reasonable expectation to the participants for what they would receive if they were in the placebo group.

3. There is insufficient data to support a conclusion about the durability of the RV144 vaccine regimen.

4. Providing the RV144 vaccine regimen to the placebo group may make h i li ibl f ibl b fi l i f h i i i ithem ineligible for any possible benefits resulting from their participation

in future trials.

5. A possibility of rare risks from the vaccine that did not show up in the RV144 trial, and the possibility of increased risk behavior, cannot be ruled , p y ,out.

However, the volunteers who were in the l b f th RV144 t i l h ld bplacebo group for the RV144 trial should be

given priority in the future for access to the RV144 vaccine regimen if it demonstrates sufficiently higher efficacy in future trials.

Even if future trials show sufficient efficacy only Even if future trials show sufficient efficacy only in specific high risk groups, there may be a presumption that the RV144 vaccine regimen

ld b i il l ffi i i l i kwould be similarly efficacious in a lower risk group, and therefore, appropriate for provision to the placebo group in the RV144 trial.

For reasons provided in recommendation #1, it is ethically acceptable to use a placebo control in a y p pfuture trial of a vaccine of similar concept to the RV144 vaccine regimen.

At present, the level of efficacy and unanswered scientific questions in the completed RV144 trialscientific questions in the completed RV144 trial justify the use of placebos in other trials.

G id i t 15 C t l G i th UNAIDS/WHO◦ Guidance point 15, Control Groups, in the UNAIDS/WHO Guidance Document states, “a placebo control is ethically acceptable when there is no HIV prevention

d lit th t h b i tifi ll lid t d ”modality that has been scientifically validated.”

For reasons provided in recommendation #1, the RV144 i i d hRV144 vaccine regimen does not meet the necessary requirements for inclusion in a prevention package.prevention package.

However, if after future trials this vaccine regimen is approved by the national regulatory authority, it must be provided in a prevention package of any future HIV preventive vaccine trialpackage of any future HIV preventive vaccine trial (Guidance point 13, Standards of Prevention, UNAIDS/WHO Guidance Document).

Protocols for future trials of the RV144 Protocols for future trials of the RV144 vaccine regimen and other HIV preventive vaccines should specify the level of efficacy required for provision of a successful product to the placebo group. This should also be included in the consent documentincluded in the consent document.

As this is the first vaccine to demonstrate a level of efficacy, and given the contribution of Thailand in reaching this result, there are compelling scientific and ethical

i f h i h hreasons to continue further vaccine research that may benefit the Thai people. The ethical reason is based on the principle of “justice as reciprocity.”

1. Given current knowledge, the Ministry of Public Health should encourage continued interpretation and expansion of the results of the RV144 trials in Thailand involving the RV144 vaccine regimen or other promising vaccine developments. g p g p

2. Researchers should seek answers to remaining scientific questions concerning the RV144 vaccine regimen in order to reach a conclusive outcome about efficacy in a timely manner..

3. The Ministry of Public Health should encourage all efforts to pursue the development of new vaccine concepts that may be beneficial to the Thai population, in particular, the segment of the population at higher risk of HIV exposurethe population at higher risk of HIV exposure.

Enhanced community participation should occur i ll i i l Th Mi i f P bli H l hin all vaccine trials. The Ministry of Public Health in its capacity of overseeing research in Thailand should ensure that researchers “consultshould ensure that researchers consult communities through a transparent and meaningful participatory process which involves them in an early and sustained manner in thethem in an early and sustained manner in the design, development, implementation, and distribution of results of bio-medical HIV prevention trials.” (Guidance point 2, Community Participation, UNAIDS/WHO Guidance Document).

Given the complexity of the RV144 trial results, the Ministry of Public Health in itsresults, the Ministry of Public Health in its capacity of overseeing research in Thailand, should seek to ensure that vaccine trial results and implications are communicated to the public in clear and understandable languagelanguage. ◦ To this end, researchers should engage

communities in consultation and dialogue throughout all stages of vaccine trials (UNAIDS/AVAC Good Participatory Practice Guidelines for biomedical prevention trials). p )