Rare Disease Prevention and Treatment: the Need for a Level Playing Field

Abstract

Pharmacogenetic tests are being used increasingly to prevent rare and potentially life-threatening adverse drug reactions. For many tests, however, cost-effectiveness is hard to demonstrate, and with the exception of a few cases, widespread implementation remains a distant prospect. Many orphan drugs for rare diseases are also not cost effective but are nonetheless normally reimbursed. In this article, we argue that the health technology assessment of pharmacogenetic tests aimed to prevent rare but severe adverse drug reactions should be on a level playing field with orphan drugs. This is supported by a number of arguments, concerning the severity, rarity and iatrogenic nature of adverse drug reactions, the distribution of benefits and costs and societal preference towards prevention over treatment.

Estimating the Effectiveness of DPYD Genotyping in Italian Individuals Suffering from Cancer Based on the Cost of Chemotherapy-Induced Toxicity

“…The severity of the impacted clinical events and the attendant costs relative to the cost of testing would also determine whether high NNG's prohibited cost effectiveness, as in the case of HLA-related Steven-Johnsons reactions and toxic epidermal necrolysis. 31 Among the four DPYD variants considered, three are indeed rare (0.2%-1.4% in white Europeans) while DPYD-HapB3 has a higher minor allele frequency (4.8%).…”

Evidence to Support Inclusion of Pharmacogenetic Biomarkers in Randomised Controlled Trials

“…For example, evidence standards could be based on risk, with biomarkers for lower risk applications requiring less evidence and regulatory oversight than those for high risk applications [145]. Recommendations could also be based on the disease being treated, similar to how orphan drugs for rare diseases are given accelerated approvals [146,147]. Biomarkers used for more serious indications could be allowed to proceed to trial with less or lower quality evidence than biomarkers for less serious conditions.…”

Why We Don’t Need “Unmet Needs”! On the Concepts of Unmet Need and Severity in Health-Care Priority Setting

“…Historically, this has left rare conditions largely untreated. However, as common conditions now, to a great extent, have access to effective treatments and given special incentives for developing treatment for rare conditions, we see a constant development of new (and expensive) treatments for rare conditions [13,14,27,51]. Should we use these developed treatments (despite cost) since they will meet unmet needs and will the fact that these needs are unmet give extra reason on top of severity to accept higher cost-effectiveness thresholds?…”

“…Given the increased discrepancy between available and required resources to meet demographic challenges, medico-technical development and raised expectations, the challenges of priority setting in health-care has been more pressing during the last years. Democratic expectations for decisions in publicly financed health-care 1 3 Health Care Analysis (2019) 27: [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] systems are that they are transparent, legitimate, and that decision-makers are held accountable for decisions. This requires that priority setting decisions are open, systematic and well-founded [11,35].…”