Comparative Assessment of Non-trial Access to Investigational Medical Products in the U.S. and Japan.

The U.S. and Japan have preapproval access systems for patients who have exhausted approved treatment options. We compare the systems of both countries and discuss some ethical concerns surrounding non-trial access to investigational drugs. Notable points of comparison of the two countries' systems include cost of non-trial access to investigational drugs and purpose of the non-trial access system. All stakeholders and the public must understand the ethical issues associated with non-trial preapproval access systems. The current non-trial access programs in both countries depends on pharmaceutical companies' voluntary decisions about whether patients get access to investigational products. Moreover, the potential for inequity of access raises ethical concerns. Non-trial preapproval access is an exceptional way to practice medicine with various ethical and safety concerns, so we suggest that the scope and eligibility for using these pathways should thus be limited.

Patient advocacy organizations' information for patients on pre-approval access to investigational treatments.

OBJECTIVE: To evaluate the availability of information regarding patient access to investigational treatments through clinical trials and non-trial pre-approval access pathways from a sample of patient advocacy organization (PAO) websites in the United States. RESULTS: We systematically analyzed the content of 118 randomly selected PAO websites to assess whether they contained information on clinical trials and non-trial pathways-e.g., the U.S. Food and Drug Administration (FDA) expanded access (EA) program and right to try-over the course of two months from February to March 2019. A majority (81%, n = 96) of PAOs provided a link to ClinicalTrials.gov, and 73% (n = 86) had their own clinical trial finder or list of relevant trials. 23% (n = 27) mentioned EA, with 8% (n = 9) providing specific resources for FDA's EA program. 8% (n = 10) provided a statement on the passage of the federal right to try law. A majority of PAO websites contained information on clinical trials, but a minority discussed non-trial pre-approval access. The lack of information on the latter highlights an area in need of improvement.

Single-Patient Expanded Access Requests: IRB Professionals' Experiences and Perspectives.

BACKGROUND: U.S. physicians may treat a patient with an investigational drug outside of a clinical trial by using the expanded access (EA) pathway or the recently created federal right to try (RTT) pathway. The EA pathway requires physicians to get prior permission from the U.S. Food and Drug Administration (FDA) and, except in emergency cases, institutional review board (IRB) approval. The perspectives of IRB professionals on the review of single-patient EA requests have not been empirically studied. METHODS: We used a cross-sectional online survey to ascertain IRB professionals' perspectives on IRB experiences with and preparedness for review of single-patient EA requests, as well as their attitudes about the importance of IRB review of such requests. Email invitations were sent to 234 IRB professionals connected to the SMART IRB platform. Approximately half of the survey questions used a Likert scale to assess respondents' agreement with specific statements. RESULTS: Eighty-three respondents completed the survey (36.4% response rate, with 228 deliverable e-mail invitations). Of the respondents, 73.5% were affiliated with an academic medical institution; 78.3% of respondents agreed that it is important for a designated member of an IRB to review single-patient EA requests before investigational drugs are used by patients. The majority indicated that local review of the EA request was important and that a single designated reviewer was sufficient (rather than full board). Further, 86.6% felt that their IRBs were prepared to review these requests, and 9.2% indicated that not all the single-patient EA requests reviewed by their IRBs in 2017 were approved. CONCLUSIONS: A large majority of IRB professionals affiliated with the SMART IRB platform who responded to this survey felt IRB review of single-patient EA requests is important and that their IRBs were prepared to handle such requests.

Ethical Issues in Gender-Affirming Care for Youth.

Transgender and gender-nonconforming (TGNC) youth who suffer from gender dysphoria are at a substantially elevated risk of numerous adverse physical and psychosocial outcomes compared with their cisgender peers. Innovative treatment options used to support and affirm an individual's preferred gender identity can help resolve gender dysphoria and avoid many negative sequelae of nontreatment. Yet, despite advances in these relatively novel treatment options, which appear to be highly effective in addressing gender dysphoria and mitigating associated adverse outcomes, ethical challenges abound in ensuring that young patients receive appropriate, safe, affordable treatment and that access to this treatment is fair and equitable. Ethical considerations in gender-affirming care for TGNC youth span concerns about meeting the obligations to maximize treatment benefit to patients (beneficence), minimizing harm (nonmaleficence), supporting autonomy for pediatric patients during a time of rapid development, and addressing justice, including equitable access to care for TGNC youth. Moreover, although available data describing the use of gender-affirming treatment options are encouraging, and the risks of not treating TGNC youth with gender dysphoria are evident, little is known about the long-term effects of both hormonal and surgical interventions in this population. To support ethical decision-making about treatment options, we encourage the development of a comprehensive registry in the United States to track long-term patient outcomes. In the meantime, providers who work with TGNC youth and their families should endeavor to offer ethically sound, patient-centered, gender-affirming care based on the best currently available evidence.

Improving Expanded Access in the United States: The Role of the Institutional Review Board.

BACKGROUND: The FDA allows patients with a serious or immediately life-threatening illness to use investigational medical products outside of clinical trials through its "expanded access" program. In response to criticism that the process to apply for expanded access is too onerous, numerous changes have been made over the last few years. These have been largely focused on the FDA and the pharmaceutical industry, while institutional review boards (IRBs)-which must approve expanded access protocols, except in emergencies when there is not time to do so-have remained relatively unstudied. We conducted a pilot study to review a sample of publicly available IRB policies from the United States to investigate how these entities handle expanded access. METHODS: We performed an online search to find publicly available policies for IRBs operating in the United States, utilizing a convenience sampling strategy, selecting the first 100 eligible policies we identified. RESULTS: Of the 95 policies reviewed, the majority (92.6%, n = 88) contained language referencing nonemergency expanded access and/or expanded access for emergency requests for a single patient. Of these 88 policies, 11.4% (n = 19) did not explicitly specify detailed procedures for handling nonemergency single-patient expanded access requests. Of the 88 policies that mentioned expanded access in nonemergency situations, 11.5% did not explicitly specify whether full IRB review was required, as was the rule at that time. There was considerable variation in other aspects of these policies, including charging patients for use of investigational products and the use of data from expanded access. CONCLUSIONS: Based on the findings of our pilot, IRB policies on expanded access vary considerably. It is often difficult to find, interpret, and understand IRB policies on expanded access. Further research is needed to determine if and to what extent this negatively impacts patient access to investigational products outside of clinical trials.

Meaningful Use of Electronic Health Records for Quality Assessment and Review of Clinical Ethics Consultation.

Evolving practice requires peer review of clinical ethics (CE) consultation for quality assessment and improvement. Many institutions have identified the chart note as the basis for this process, but to our knowledge, electronic health record (EHR) systems are not necessarily designed to easily include CE consultation notes. This article provides a framework for the inclusion of CE consultation notes into the formal EHR, describing a developed system in the Epic EHR that allows for the elaborated electronic notation of the CE chart note. The implementation of the "meaningful use" criteria for EHR, mandated by the Health Information Technology for Economic and Clinical Health (HITECH) Act of 2009, requires that health professionals meet certain standards for quality, efficiency, and safety, all of which overlap with the goals of standardization, peer review, and quality improvement within CE consultation.

Charlie Gard and the Limits of Parental Authority.

The parents of Charlie Gard, who was born August 4, 2016, with an exceedingly rare and incurable disease called mitochondrial DNA depletion syndrome, fought a prolonged and heated legal battle to allow him access to experimental treatment that they hoped would prolong his life and to prevent his doctors from withdrawing life-sustaining care. Charlie's clinicians at the Great Ormond Street Hospital in London believed that the brain damage Charlie had suffered as a result of frequent epileptic seizures, along with many other severe disabilities, would render any innovative therapy futile, and they disagreed with his parents' wishes to use an experimental therapy. They felt it in Charlie's best interest that he be allowed to die. A battle ensued among Charlie's parents, his doctors, and a guardian who had been appointed to represent him that drew the attention of politicians and prominent persons from all over the world. The case was much in the news over the past year, but it has also been frequently misunderstood.