The ethical value—and to some scholars, necessity—of providing trial patients with post-trial access (PTA) to an investigational drug has been subject to significant attention in the field of research ethics. Although no consensus has emerged, it seems clear that, in some trial contexts, various factors make PTA particularly appropriate. We outline the atypical aspects of psychedelic clinical trials that support the case for introducing the provision of PTA within research in this field, including the broader legal status of psychedelics, the (...) nature of the researcher-therapist/participant relationship, and the extended time-frame of the full therapeutic process. As is increasingly understood, the efficacy of psychedelic-assisted psychotherapy is driven as much by extrapharmacological elements and the cultural therapeutic container as by the drug itself. As such, we also advocate for a refocusing of attention from post-trial access to a broader concept encompassing other elements of post-trial care. We provide an overview of some of the potential post-trial care provisions that may be appropriate in psychedelic clinical trials. Although the World Medical Association’s Declaration of Helsinki calls on researchers, sponsors, and governments to make provisions for post-trial access, such provision may feel impracticable or out-of-reach within psychedelic trials that are already constrained by a high resource demand and significant bureaucratic burden. We show how conceiving of post-trial provision as an integral site of the research process, and an appropriate destination for research funding, will serve to develop the infrastructure necessary for the post-legalisation psychedelic medicine ecosystem. (shrink)

There is growing interest among pharmaceutical policymakers in how to “disinvest” from subsidized medicines. This is due to both the rapidly rising costs of healthcare and the increasing use of accelerated and conditional reimbursement pathways which mean that medicines are being subsidized on the basis of less robust evidence of safety and efficacy. It is crucial that disinvestment decisions are morally sound and socially legitimate, but there is currently no framework to facilitate this. We therefore reviewed the bioethics literature in (...) order to identify ethical principles and concepts that might be relevant to pharmaceutical disinvestment decisions. This revealed a number of key ethical considerations—both procedural and substantive—that need to be considered when making pharmaceutical disinvestment decisions. These principles do not, however, provide practical guidance so we present a framework outlining how they might be applied to different types of disinvestment decisions. We also argue that, in this context, even the most rigorous ethical reasoning is likely to be overridden by moral intuitions and psychological biases and that disinvestment decisions will need to strike the right balance between respecting justifiable moral intuitions and overriding unjustifiable psychological impulses. (shrink)

This paper discusses the need to focus on the dignity of human participants as a legal and ethical basis for providing post-trial access to healthcare. Debate about post-trial benefits has mostly focused on access to products or interventions proven to be effective in clinical trials. However, such access may be modelled on a broad fair benefits framework that emphasises both collateral benefits and interventional products of research, instead of prescribed post-trial access alone. The wording of the current version of the (...) Declaration of Helsinki could in fact be interpreted to broaden the scope to include other collateral benefits by applying such a broad fair benefits framework. We argue that this possibility should be utilised by low and middle income countries’ health research ethics committees in order to ensure that research participants who enrol in clinical trials so as to receive medical care continue to access care after the trial is concluded, as befits their dignity. Although each LMIC has unique concerns, nonetheless there are common challenges based especially on emerging issues, such as post-trial access to healthcare. Accordingly, the South African perspective is used to draw lessons that can benefit other LMICs. (shrink)

Increasing ethical attention and debate is focusing on whether individuals who take part in clinical trials should be given access to post-trial care. However, the main focus of this debate has been upon drug trials undertaken in low-income settings. To broaden this debate, we report findings from interviews with individuals (n = 24) who participated in a clinical trial of a closed-loop system, which is a medical device under development for people with type 1 diabetes that automatically adjusts blood glucose (...) to help keep it within clinically recommended ranges. Individuals were recruited from UK sites and interviewed following trial close-out, at which point the closed-loop had been withdrawn. While individuals were stoical and accepting of the requirement to return the closed-loop, they also conveyed varying degrees of distress. Many described having relaxed diabetes management practices while using the closed-loop and having become deskilled as a consequence, which made reverting back to pre-trial regimens challenging. Participants also described unanticipated consequences arising from using a closed-loop. As well as deskilling, these included experiencing psychological and emotional benefits that could not be sustained after the closed-loop had been withdrawn and participants reevaluating their pre- and post-trial life in light of having used a closed-loop and now perceiving this life much more negatively. Participants also voiced frustrations about experiencing better blood glucose control using a closed-loop and then having to revert to using what they now saw as antiquated and imprecise self-management tools. We use these findings to argue that ethical debates about post-trial provisioning need to be broadened to consider potential psychological and emotional harms, and not just clinical harms, that may result from withdrawal of investigated treatments. We also suggest that individuals may benefit from information about potential nonclinical harms to help make informed decisions about trial participation. (shrink)

Purpose We examine the levels of post-trial responsibility ascribed to different stakeholders, following a community-based clinical trial and how the ‘responsibility’ is understood. Methods We employed photovoice, unstructured observations and key informant interviews to gain insights into contexts of access to care following transition to the public health system post trial. We used an inductive narrative analysis to explore experiences and understandings of post-trial access. Results In their photovoice stories, many participants expressed a sense of abandonment after the trial. This (...) was viewed as a contributing factor to failing to re-engage with care available in the public health system. This led to the experiences of loss as some trial participants defaulted and died. Research investigators, department of health participants and sponsor agreed that PTA was especially important for communities in resource-limited settings. The government has an obligation towards its citizens while researchers have a responsibility to ensure a smooth transition of patients to public clinics. Sponsors have a responsibility to ensure that the trial is conducted in accordance with the protocol and post-trial agreements are in place and adhered to. Research partnerships among stakeholders were affected by power imbalances making it difficult to negotiate and plan for post-trial care responsibilities. Conclusions The research community still struggles with understanding the scope of PTA responsibilities. Power dynamics between public health actors and research sponsors need to be managed to ensure that government involvement is not tokenistic. The responsibility of trial participants and ethics committees needs to be investigated further. Data are available upon request. (shrink)

Clinical trials are essential to establish the safety and efficacy of investigational products, contributing to risk/benefit assessments that ultimately determine whether these products meet the criteria for market authorisation. Clinical trials are also an important source of revenue and expertise generation for countries in which they are conducted. In developing countries, they represent substantial foreign direct investment. In spite of the substantial capital input that clinical trials require, the issue of funding post-trial access to beneficial therapies remains contentious, especially in (...) resource-limited settings. In this article, we explore this situation and propose mechanisms to establish ‘win-win’ situations where both patients and clinical trial sponsors derive benefit from post-trial access programmes in low- and middle-income countries. (shrink)