Established in 2006 by a bequest from William J. Prager, to honour the career of Israel Mordecai Rabinowitch, M.D., C.M, 1917, D.Sc. 1932 (1890-1983), described as the father of clinical chemistry in Canada. Dr. Rabinowitch joined the McGill Faculty of Medicine in 1922, and helped build the Metabolism and Toxicology Department at Montreal General Hospital. He was one of the first medical scientists to test insulin, and by the 1930s, his diabetic clinic was the second largest in North America. He also organized and commanded Canada’s Chemical Warfare Defense Laboratory during World War II, and developed educational materials directed at protecting civilians from chemical warfare agents.
Awarded on the basis of academic merit by the Faculty of Medicine, on the recommendation of the Biomedical Ethics Unit, to one or more Master’s or PhD students pursuing studies through the Biomedical Ethics Unit. Preference will be given to graduate students pursuing theses that are in line with Dr. Rabinowitch’s medical and scientific legacy, or commitment to Jewish ethics and jurisprudence. Value: Approximately $7,500 for one year. Pending demonstration of progress towards a completed thesis, award can be renewed for a second year.
We invite students to apply for the fellowship in a short letter (1-2 pages) outlining their academic performance record, research interests, and how their research interests align with the legacy of Dr. Rabinowitch. Please submit your letter to heike.faerber [at] mcgill.ca by April 15, 2020.
Egalitarian Justice, Disability, and Genetic Interventions
Abstract: The literature on the relationship between justice and genetic intervention has been ongoing since, most notably, the mid-90s with the most common line drawn between justice and genes being the value of equality of opportunity. The popular claim in question is that equality of opportunity requires the genetic modification of persons with congenital disabilities or the prenatal genetic disposition to them. Different contributors have different understandings of equality of opportunity that support this claim, but the claim has a near consensus nevertheless. In this paper, I argue that it’s not the case that equality of opportunity demands the genetic modification of such persons. I take this to be the case for two reasons. First, when theorists think this demand flows from equality of opportunity, they mistakenly confuse opportunities with outcomes. To help
Illustrate this point, I consider two competing and widely held views about equality of opportunity and show that disabilities as such do not undermine equality of opportunity. The two outcomes they aim to produce by way of genetic interventions are the mitigation or elimination of so-called "natural inequalities" or the establishment of rough equality in cognitive capacity (the capacity for higher-level practical reasoning). Second, i argue that these two outcomes are plagued with conceptual and practical issues and should not serve as a basis for requirements of egalitarian justice. In short, my claim is that the genetic modification of persons with congenital disabilities is not a requirement of egalitarian justice, at least on the grounds of equality of opportunity or the purported outcomes genetic interventions are supposed to bring about.
Expanded Access Therapies and Terminally Ill Jewish Patients: Medical and Religious Decision-Making During End-Stage Disease
Abstract: The FDAs expanded drug access program, alternatively referred to as the compassionate use program, allows patients with serious diseases or life-threatening conditions to gain access to investigational medical products without enrolling in a clinical trial. This program has a remarkably high approval rate approximately 99% of all applications are approved
Gaining access to an otherwise inaccessible treatment option is thought to be a boon for patients, but not all patients are aware of the potential risks that accompany these interventions. The risk-benefit profiles for investigational therapies are often nebulous. By definition these therapies lack complete clinical data on safety and efficacy. Furthermore, as some of these medications are in the early phases of clinical development, they lack data from human trials. Thus, the utility of these therapies may be unknown.
Many patients do not understand the drug development pipeline, leading to erroneous expectations. Physicians must balance patient expectations and safety when discussing the use of investigational therapies. This balancing of patient expectations and safety is complicated by differences in patient attitudes towards risk and their definition of a successful medical intervention. These concerns are amplified when working with religiously devout patients whose faith places an emphasis on the maintenance of human life. Patients of Orthodox Jewish faith are particularly vulnerable given their religious views on the sanctity of life and terminal illness.
Some denominations of Orthodox Judaism encourage patients and their families to take what many health care professionals consider to be “extreme measures” when treating a terminal illness. This project aims to explore the vulnerabilities of terminally ill Orthodox Jewish patients who intend to access investigational therapies via the FDA’s expanded access program.
Thus, the goals of this project are to develop a three-part framework which will help guide terminally ill Orthodox Jewish patients and their physicians who may attempt to gain entry into the expanded access program. The three sections include 1) Determination of religious and medical inclusion/ exclusion criteria for these patients. 2) Coordination and communication between Rabbis, physicians, the patient, and their family with regards to realistic medical goal setting. 3)Possible religious and medically permissible alternatives to the expanded access program.
Measuring the Clinical Impact of Participating in Pediatric Oncology Trials
Abstract: Despite medical advancements to combat pediatric malignancies, the most common disease-related cause of death in Canadian children and the fourth leading cause of death in US children aged 1 to 18 years is cancer. However, the development of safe and effective therapies for treating children with cancer confronts major challenges. First, children cannot legally provide informed consent when enrolling in clinical trials, owing to their status as minors. Second, since pediatric cancers are rare, clinical trials face difficulty in attracting funding and recruiting patient participants. Last, there is an inherent hesitancy to expose vulnerable children to unproven drugs that have a limited evidentiary basis for safety and involve greater uncertainty about risk.
Ethical pursuit of pediatric cancer trials therefore depends on the ability to convey accurate information about the risks and the clinical impact associated with study participation. It also requires selecting treatments for testing that have the greatest prospect of impacting care. However, both of these are complicated by the limited systematic evidence about the clinical impact associated with pediatric cancer trial participation. In particular, there is presently no way of telling a guardian and/or prospective child how likely their participation in a trial will lead to major advances in pediatric cancer care. Nor are there established ways of soliciting and pooling expert judgements so that the most promising interventions are prioritized for clinical testing, or so that ethical evaluation of trial protocols reflects an accurate appraisal of potential benefit.
Thus, this project aims to predict the proportion of pediatric cancer trials (and the patients enrolled in these trials) that lead to impact progress in pediatric cancer treatment. Secondarily, I will build a predictive model to investigate which types of trials are associated with a greater probability of impacting future treatment.
The imprecision of precision medicine in cancer drug development: a systematic comparative analysis
Abstract: Precision medicine (PM) in cancer typically involves matching patients to treatments based on molecular characteristics of their tumour. PM drug development is often viewed as more rapid and requiring fewer patients than non-precision medicine approaches. As drug development is an expensive process that exposes patients to significant risks, this vision for PM drug development is highly attractive. This thesis presents the rationale and results of a systematic comparative analysis of all published trials in first-in-class, novel oncology drugs that were first FDA-approved between 2009-2014. Fourteen drugs were included, five in the PM cohort and nine in non-PM cohort. We collected 339 trials – 109 trials in PM, and 230 trials in non-PM. PM took a comparable amount of time (median 1750 days in PM v. 1825 days in non-PM; range 1120-3458 in PM vs. 929-3127 in non-PM) and patients (median total n 1909 in PM v. 1265 in non-PM; range 986-2610 in PM v. 655-5009 in non-PM) between the first efficacy trial and the receipt of their first FDA licensing event when compared to non-PM. The PM cohort explored a comparable number of drug-indication trajectories, was more likely to use surrogate endpoints than "hard" clinical endpoints, was just as likely to have patients experiencing a Grade 3-4 adverse event, and dropped biomarker for eligibility in later trajectories when compared to non-PM. The thesis is a small, observational, retrospective analysis that may not be generalizable to all novel oncology drugs. Nevertheless, these findings suggest that precision medicine may not be as effective in sparing time and patients in drug development. Going forward, institutions, sponsors, and policymakers should be aware of this thesis's results and take the findings into consideration for actions concerning precision medicine drug development in oncology.
Jewish law, Jewish ethics and Quebec's culture: potential influences on the experience of infertility for Hasidic women in Quebec
Abstract: The aim of this thesis is to examine reproductive technologies and infertility from the perspective of Orthodox Jewish ethics, law and culture. Treating infertility is a complex process; individuals vary in their course of treatment, taking into account their medical situation, religious beliefs, prevailing cultural norms, reproductive policy in their jurisdiction, financial constraints, and their community context. For Orthodox and ultra-Orthodox Jews, this context includes a religious and cultural imperative to procreate, as well as religious law and social preference dictating the most preferred types of family. Judaism is a particularly pronatalist religion, and has a large body of halakhic text on reproductive technologies. Jewish people living in North America may also be influenced in their infertility experience by the policies and cultural norms of the society in which they live. This thesis examines the aspects of halakha (Jewish law), Quebec policy, Orthodox Jewish ethics, and ultra-Orthodox and Hasidic Jewish culture that are likely to influence the experience of infertility for Hasidic Jewish women in Quebec. Orthodox Judaism has a strong legacy of opinion defining the nature of family and the importance of genetics. This paper examines the aspects of Judaism and Hasidic culture that might strongly influence this experience, and also examines aspects of Quebec's history and current policy that may also influence this experience, albeit from a different angle.
The moral efficiency of clinical trials in anti-cancer drug development
Drug development research programmes can be very extensive, costly and risky. In many cases, clinical trials of a drug continue after regulatory approval to test new indications, combinations, populations, doses and schedules. The efficiency of drug development is usually considered in economic terms that only take into account the cost of bringing a drug to market, and often neglect costs that are incurred after licensure is achieved. In what follows, we describe approaches for measuring and evaluating the moral efficiency of drug development, considering inputs such as the welfare of human subjects, and outputs such as scientific value and clinically useful information. This may better capture the ethical landscape of drug development, identify inefficiencies and bring to light dynamics that are invisible at the single-trial level. Here, we conduct a series of analyses, moving from particular cases to general principles. First, systematic review and meta-analytic methods are used to characterize patterns of patient risk and benefit, and to examine measures of clinical impact among clinical trials of sunitinib in indications that were not approved by the FDA at the time the trial was launched. Our methods are then applied to a comparison of imatinib with two of its "me too" successors, dasatinib and nilotinib. These projects reveal a large volume of research after a drug is approved by the FDA and cases of worsening risk and benefit over the course of drug development. Next, we conduct two retrospective cohort studies capturing first monotherapy and then combination therapy trials of anti-cancer drugs first approved by the FDA between 2005-2007. These quantify the clinical payoff and investment of human research subjects among indications and combinations that were first launched into testing after a drug's approval. Finally, these insights are used to define and develop the concept of "clinical agnosticism," the uncertainty of clinical efficacy that arises following positive hypothesis-generating clinical trials that lack confirmatory follow-up. This evaluation of the moral efficiency of drug development has implications for the practice of independent ethics review, monitoring of ongoing trials, interpretation of clinical trial results, regulatory approval and policy setting.