Joe T R Clarke1, Doug Coyle2, Gerald Evans3, Janet Martin4, Eric Winquist4. 1. Hospital for Sick Children and University of Toronto, Toronto, ON, Canada. Electronic address: joeclarke@sympatico.ca. 2. University of Ottawa, Ottawa, ON, Canada. 3. Kingston General Hospital and School of Medicine, Queen's University, Kingston, ON, Canada. 4. Schulich School of Medicine & Dentistry, Western University, London, ON, Canada; London Health Sciences Centre, London, ON, Canada.
Abstract
BACKGROUND: The designation of a disease as "rare" is associated with some substantial benefits for companies involved in new drug development, including expedited review by regulatory authorities and relaxed criteria for reimbursement. How "rare disease" is defined therefore has major financial implications, both for pharmaceutical companies and for insurers or public drug reimbursement programs. All existing definitions are based, somewhat arbitrarily, on disease incidence or prevalence. OBJECTIVES: What is proposed here is a functional definition of rare based on an assessment of the feasibility of measuring the efficacy of a new treatment in conventional randomized controlled trials, to inform regulatory authorities and funding agencies charged with assessing new therapies being considered for public funding. METHODS: It involves a five-step process, involving significant negotiations between patient advocacy groups, pharmaceutical companies, physicians, and public drug reimbursement programs, designed to establish the feasibility of carrying out a randomized controlled trial with sufficient statistical power to show a clinically significant treatment effect. RESULTS AND CONCLUSIONS: The steps are as follows: 1) identification of a specific disease, including appropriate genetic definition; 2) identification of clinically relevant outcomes to evaluate efficacy; 3) establishment of the inherent variability of measurements of clinically relevant outcomes; 4) calculation of the sample size required to assess the efficacy of a new treatment with acceptable statistical power; and 5) estimation of the difficulty of recruiting an adequate sample size given the estimated prevalence or incidence of the disorder in the population and the inclusion criteria to be used.
BACKGROUND: The designation of a disease as "rare" is associated with some substantial benefits for companies involved in new drug development, including expedited review by regulatory authorities and relaxed criteria for reimbursement. How "rare disease" is defined therefore has major financial implications, both for pharmaceutical companies and for insurers or public drug reimbursement programs. All existing definitions are based, somewhat arbitrarily, on disease incidence or prevalence. OBJECTIVES: What is proposed here is a functional definition of rare based on an assessment of the feasibility of measuring the efficacy of a new treatment in conventional randomized controlled trials, to inform regulatory authorities and funding agencies charged with assessing new therapies being considered for public funding. METHODS: It involves a five-step process, involving significant negotiations between patient advocacy groups, pharmaceutical companies, physicians, and public drug reimbursement programs, designed to establish the feasibility of carrying out a randomized controlled trial with sufficient statistical power to show a clinically significant treatment effect. RESULTS AND CONCLUSIONS: The steps are as follows: 1) identification of a specific disease, including appropriate genetic definition; 2) identification of clinically relevant outcomes to evaluate efficacy; 3) establishment of the inherent variability of measurements of clinically relevant outcomes; 4) calculation of the sample size required to assess the efficacy of a new treatment with acceptable statistical power; and 5) estimation of the difficulty of recruiting an adequate sample size given the estimated prevalence or incidence of the disorder in the population and the inclusion criteria to be used.
Authors: M K Javaid; L Forestier-Zhang; L Watts; A Turner; C Ponte; H Teare; D Gray; N Gray; R Popert; J Hogg; J Barrett; R Pinedo-Villanueva; C Cooper; R Eastell; N Bishop; R Luqmani; P Wordsworth; J Kaye Journal: Orphanet J Rare Dis Date: 2016-11-08 Impact factor: 4.123
Authors: Andrea Romigi; Giuseppe Vitrani; Temistocle Lo Giudice; Diego Centonze; Valentina Franco Journal: Drug Des Devel Ther Date: 2018-08-30 Impact factor: 4.162
Authors: Andrew E Mulberg; Christina Bucci-Rechtweg; Joseph Giuliano; David Jacoby; Franklin K Johnson; Qing Liu; Deborah Marsden; Scott McGoohan; Robert Nelson; Nita Patel; Klaus Romero; Vikram Sinha; Sheela Sitaraman; John Spaltro; Vivian Kessler Journal: Orphanet J Rare Dis Date: 2019-02-08 Impact factor: 4.123