Live Blogging: Post-Trial Responsibilities Conference, Session 3

By Robin Pierce

Session 3 of the Post Trial Responsibilities Conference, Lessons Learned, featured four speakers who have been involved in the conduct of trials for which post trial access was an issue. Moderated by Petrie-Flom Executive Director, Holly Fernandez Lynch, the session aimed to better understand real world experiences implementing post-trial responsibilities, including both successes and failures, and to more clearly articulate and assess the complexities involved. To do this, the speakers used case studies drawn from actual trials conducted around the world.

The first case study, presented by Joseph Millum of NIH, dealt with NIH-funded global HIV research, covered by the NIH policy on post-trial access to ARVs. Confronting the tough issues at the outset, Millum stated plainly that if there were no post trial access in the study at hand, which aimed to evaluate third line treatment options for HIV patients failing other regimens, there would be no way for affected participants to obtain the drugs that they needed to stay alive after the study. Here, Millum identified two key challenges – 1) access to drugs and 2) obtaining clinical care.

Millum devoted the rest of the discussion to describing the creation and implementation of a two part solution in which the manufacturers negotiated an agreement to provide darunavir, etravirine, and raltegravir free of charge for two years after study participation. Another element of the solution was created out of a recognition that in order for drugs to be administered at study sites, they had to be part of a study. Therefore, a final step was added to the study in which participants taking the drugs were given the option of staying in the study for an additional 96 weeks. For this, researchers tailored the consent process to state that after the study, the participant and his or her doctor will decide what treatment the participant should have and that study staff would discuss how the participants may be able to obtain the drugs post-trial.

In concluding discussion of his case study, Millum identified several important issues that should be focused on in devising an appropriate post trial plan. 1. Who is responsible for PTA? 2. A single party alone cannot provide PTA, rather it requires collaboration 3. For how long after the trial should PTA be provided? 4. Access to what? 5. Access how? PTA is usually thought of as post trial, but here it was incorporated into a new trial.

The next speaker in the Lessons Learned session was Nancy Padian from UC Berkeley. Her case study was of a Phase 3 effectiveness trial of diaphragm and lubricant gel for HIV prevention among women in Zimbabwe and South Africa. She identified at the outset that among the most important issues for the researchers regarding PTA were provision of the intervention, other health services offered during the trial, and other resources provided during the trial, e.g. infrastructure.

In thinking through post-trial access in this case study, Padian noted that she and her team had failed to account for the fact that because recruitment was rolling, not every subject would finish the trial at the same time; some would finish before others, precluding the possibility of knowing whether the intervention worked at the time their participation ended.  Their solution, after meeting with ethicists and lawyers, was to come up with a counseling strategy explaining what they knew and did not yet know regarding efficacy and that the participant and her provider should decide how to proceed. They also attached a quiz to the IC form to ensure that participants understood sufficiently to make a decision.

They offered: risk reduction counseling to all participants, condom provision and counseling, STI treatment services, cervical CA diagnosis and treatment, partner testing and referrals, all of which exceeded the local standard of care.

In explaining why the Global Best Standard was not offered in the trial, Padian discussed issues of sustainability of care, saying that if the “best standard” cannot be attained and sustained in the host community, it may not be relevant to the institutions or practices of host community. Therefore, she urged, researchers should aspire to the “highest attainable and sustainable standard” – during and after research.

Finally, Padian discussed the infrastructural responsibilities that they assumed, many of which lingered well into the post-trial period. They built brick and mortar clinics during the trial and provided fleets of vehicles. And they trained a huge number of staff, who went on to serve other trials in the country.

Walter Strauss from Merck told the story of Indinavir (CRIXIVAN). Tracing the discovery process back to the 1990’s, Strauss described not only the scientific developments but also the human elements, citing the death of a lead chemist in the Pan Am Lockerbie plane disaster. Strauss discussed trials that had taken place in the US, Europe, and Australia, and then discussed the monotherapy trial in Brazil, which was Merck’s first trial in a then regarded “developing country”.

Strauss identified as key factors that drove design of PTA :1) scientific/medical value  2) responsibility to participants 3) access to treatment and 4) potential risks associated with treatment discontinuation. Other key observations included PTA considerations varied by country and  regard for multiple stakeholders.

The last speaker of the session was Laurie Letvak of Novartis calling in, grounded by a broken foot. She gave an overview of considerations in a Gleevec (imatinib mesylate) trial in CML. She emphasized the need to evolve one’s strategy over time. In her overview she proposed the following considerations: is the drug already marketed or is it not yet approved for any indication, are there alternative treatments available (for patients on drug/placebo), and what other elements of care should be the responsibility of the company? But noted that medical care is not the remit of a company conducting research. Letvak repeated the admonition to try to anticipate what kind of data will need to be collected.  Letvak offered some final thoughts – 1) proactive planning and anticipation of scenarios 2) anticipate extent of data collection 3) need to communicate and align expectations of all stakeholders, consider local regulations and limitations.