Showing papers by "Jerome Amir Singh published in 2017"

Results from the Workshop “Problem Formulation for the Use of Gene Drive in Mosquitoes”

Abstract: Reducing the incidence of malaria has been a public health priority for nearly a century. New technologies and associated vector control strategies play an important role in the prospect of sustained reductions. The development of the CRISPR/Cas9 gene editing system has generated new possibilities for the use of gene-drive constructs to reduce or alter vector populations to reduce malaria incidence. However, before these technologies can be developed and exploited, it will be necessary to understand and assess the likelihood of any potential harms to humans or the environment. To begin this process, the Foundation for the National Institutes of Health and the International Life Sciences Institute Research Foundation organized an expert workshop to consider the potential risks related to the use of gene drives in Anopheles gambiae for malaria control in Africa. The resulting discussion yielded a series of consensus points that are reported here.

Undue inducement: a case study in CAPRISA 008.

Abstract: Participant safety and data integrity, critical in trials of new investigational drugs, are achieved through honest participant report and precision in the conduct of procedures. HIV prevention post-trial access studies in middle-income countries potentially offer participants many benefits including access to proven efficacious but unlicensed technologies, ancillary care that often exceeds local standards-of-care, financial reimbursement for participation and possibly unintended benefits if participants choose to share or sell investigational drugs. This case study examines the possibility that this combination of benefits may constitute an undue inducement for some participants in middle-income countries, where economic challenges are prevalent. A case study is presented of a single participant in a cohort of 382 participants who used concealment, fabrication and deception to ensure eligibility for a post-trial access study of an unlicensed HIV prevention technology at potential risk to her health and that of her fetus. A root cause analysis revealed her desire to access HIV prevention during an unplanned pregnancy with a partner whose faithfulness was in question. Researchers should consider implementation of systems to efficiently identify similar cases without inconveniencing the majority of participants Trial registration number NCT01691768.

Ethical and Legal Considerations for Realising Post-trial Access of Novel Experimental Interventions: Lessons from the CAPRISA 004 Trial

Abstract: The CAPRISA 004 trial, a phase 2b, double-blind, randomised, placebo-controlled trial, revolutionised the HIV prevention arena, particularly the microbicide field, by becoming the first study to demonstrate efficacy of a HIV microbicide product. The trial found that 1% tenofovir gel was 39 % efficacious in preventing vaginal HIV infection, and 51% efficacious in preventing herpes simplex virus type 2 (HSV-2) amongst women [1]. The study also found that women who adhered to the prescribed regimen of two doses of tenofovir gel for more than 80% of their sex acts had a 54% lower risk of HIV infection. Despite the trial’s success, as the CAPRISA 004 trial was a phase 2b trial, drug regulatory authorities—such as the United States Federal Drug Administration (FDA) and South Africa’s Medicine Control Council (MCC)—required additional confirmatory evidence from a phase 3 trial before registering and license the product as a HIV prevention agent for females. In the aftermath of the CAPRISA 004 trial, even if a follow-up phase 3 confirmatory trial yielded evidence in support of the CAPRISA 004 trial’s findings, it was realistic to expect that tenofovir gel would only obtain licensure 4–5 years after the conclusion of the CAPRISA 004 trial. Such a delay raised profound ethical, legal and human rights issues regarding CAPRISA 004 trial participants’ access to tenofovir gel during the period between the conclusion of the CAPRISA 004 trial and the results of the follow-up phase 3 confirmatory trial (the FACTS-001 trial [2]), and moreover, between the conclusion of the CAPRISA 004 trial and its potential licensure by regulatory authorities. How CAPRISA considered and realised its post-trial obligations towards relevant participants of the CAPRISA 004 trial may be instructive to others facing similar dilemmas.