What Precision Medicine Can Learn from Rare Genetic Disease Research and Translation

Abstract

The goal of this article is to examine the intersections of precision health and rare diseases. Specifically, we propose 3 lessons from the last decade of applying genomics to rare diseases: (1) precision can end one odyssey and start another;(2) precise interventions can exacerbate health disparities and create other ethical dilemmas; and (3) democratization of data will transform research and translation. By studying experiences of patients with rare diseases, researchers, clinicians, and policymakers can anticipate similar challenges in precision medicine and hopefully mitigate potential harms or injustices. Rare Diseases and Precision MedicineMore than 25 million Americans suffer from one of over 7000 rare conditions, 1 each one of which has an incidence of 1 in 200 000 or less. The rarity of these conditions creates challenges, such as convincing agencies and companies to fund development of effective and affordable treatments, provide programmatic support, and facilitate patient interaction and support opportunities. content/uploads/2018/03/ALK-Positive_Outreach-Update_20180315.pdf. Published March 15, 2018. Accessed March 26, 2018. 23. Arbour KC, Riely GJ. Diagnosis and treatment of anaplastic lymphoma kinasepositive non-small cell lung cancer.

Objectivity in rare disease research: A philosophical approach

“…These in turn require such things as statistical significance, unbiased data, and impartial interpretation-the reality of which is problematic in rare disease research due in part to small patient numbers, low priority for medication/treatment development, and restrictive inclusion/exclusion criteria in dug trials (Gericke et al, 2005;Tabor & Goldenberg, 2018). These in turn require such things as statistical significance, unbiased data, and impartial interpretation-the reality of which is problematic in rare disease research due in part to small patient numbers, low priority for medication/treatment development, and restrictive inclusion/exclusion criteria in dug trials (Gericke et al, 2005;Tabor & Goldenberg, 2018).…”

“…This concern carries with it the possibility that a false judgement claim regarding the reliability of results will be made and/or left unchallenged by the researcher or wider scientific community (Jokula, 2016). In areas such as rare disease, where significant gaps currently exist, the addition of knowledge that does not advance science, or improve understanding, can have wide-reaching negative implications, including reluctance of funders to provide ongoing research support, increased barriers to participating in clinical trials, and stagnant care and treatment options (Tabor & Goldenberg, 2018). In areas such as rare disease, where significant gaps currently exist, the addition of knowledge that does not advance science, or improve understanding, can have wide-reaching negative implications, including reluctance of funders to provide ongoing research support, increased barriers to participating in clinical trials, and stagnant care and treatment options (Tabor & Goldenberg, 2018).…”

“…As the number of individuals living with a particular disease is relatively small-and there are a significant number of rare conditions-an array of challenges complicates the knowledge development in this area of study (Institute of Medicine Committee on Accelerating Rare Diseases Research & Orphan Products, 2010). Some of those difficulties include attracting public and private funding for research and development, recruiting enough numbers of research participants for clinical studies, appropriately using clinical research designs for small populations, and securing adequate expertise at the federal level that reviews rare disease research applications or authorizes the marketing of medications or treatments for rare conditions (Gericke et al, 2005;IOM, 2010;Jokula, 2016;Tabor & Goldenberg, 2018). These challenges make it difficult for researchers to recruit an adequate number of patients to reach scientifically valid conclusions (Faber & Fonseca, 2014;Gupta, 2012).…”

“…Tabor and Goldenberg (2018) outline ethical dilemmas associated with rare disease research, including perceived lack of validity/reliability resulting from small sample sizes. For instance, if objectivity requires universality, indisputably rare disease knowledge development cannot be objective.…”

“…This tension between traditionally 'reliable' science and the influence of subjective bias is increasingly present in the rare disease literature, forming the basis of procedural and ethical discussions. Tabor and Goldenberg (2018) outline ethical dilemmas associated with rare disease research, including perceived lack of validity/reliability resulting from small sample sizes. Ethical implications of increased ties to industry with respect to funding are discussed by Gericke, Riesberg, and Busse (2005) through the lens of utilitarian bioethics.…”