Orphan Therapies: Making Best Use of Postmarket Data

Maro, Judith C.; Brown, Jeffrey S.; Pan, Meichen

doi:10.1007/s11606-014-2882-1

Cited by 4 publications

(1 citation statement)

References 38 publications

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“…Other authors are suggesting that real world data, pharmacovigilance protocols and prospective studies will also help in the growth of knowledge on biosimilars [55]. However, pharmacovigilance databases may be inadequate in rare diseases, thus fueling the search for new tools of analysis [94].…”

Section: Problematic Generic Substitutionsmentioning

confidence: 99%

Generic Substitution of Orphan Drugs for the Treatment of Rare Diseases: Exploring the Potential Challenges

Paolo

Arrigoni

2018

Drugs

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Generic drugs are important components of measures introduced by healthcare regulatory authorities to reduce treatment costs. In most patients and conditions the switch from a branded drug to its generic counterpart is performed with no major complications. However, evidence from complex diseases suggests that generic substitution requires careful evaluation in some settings and that current bioequivalence criteria may not always be adequate for establishing the interchangeability of branded and generic products. Rare diseases, also called orphan diseases, are a group of heterogeneous diseases that share important characteristics: in addition to their scarcity, most are severe, chronic, highly debilitating, and often present in early childhood. Finding a treatment for a rare disease is challenging. Thanks to incentives that encourage research and development programs in rare diseases, several orphan drugs are currently available. The elevated cost of orphan drugs is a highly debated issue and a cause of limited access to treatment for many patients. As patent protection and the exclusivity period of several orphan drugs will expire soon, generic versions of orphan drugs should reach the market shortly, with great expectations about their impact on the economic burden of rare diseases. However, consistent with other complex diseases, generic substitution may require thoughtful considerations and may be even contraindicated in some rare conditions. This article provides an overview of rare disease characteristics, reviews reports of problematic generic substitution, and discusses why generic substitution of orphan drugs may be challenging and should be undertaken carefully in rare disease patients.

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Section: Problematic Generic Substitutionsmentioning

confidence: 99%

Generic Substitution of Orphan Drugs for the Treatment of Rare Diseases: Exploring the Potential Challenges

Paolo

Arrigoni

2018

Drugs

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Distributed Networks of Databases Analyzed Using Common Protocols and/or Common Data Models

Toh

Pratt

Klungel

et al. 2019

Pharmacoepidemiology

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Using a meta-narrative literature review and focus groups with key stakeholders to identify perceived challenges and solutions for generating robust evidence on the effectiveness of treatments for rare diseases

Tingley

Coyle

Graham

et al. 2018

Orphanet J Rare Dis

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IntroductionFor many rare diseases, strong analytic study designs for evaluating the efficacy and effectiveness of interventions are challenging to implement because of small, geographically dispersed patient populations and underlying clinical heterogeneity. The objective of this study was to integrate perspectives from published literature and key rare disease stakeholders to better understand the perceived challenges and proposed methodological approaches to research on clinical interventions for rare diseases.MethodsWe used a meta-narrative literature review and focus group interviews with key rare disease stakeholders to better understand the perceived challenges in generating and synthesizing treatment effectiveness evidence, and to describe various research methods for mitigating these identified challenges. Data from both components of this study were synthesized narratively according to research paradigms that emerged from our data.ResultsResults from our meta-narrative literature review and focus group interviews revealed three fundamental challenges in generating robust treatment effectiveness evidence for rare diseases: i) limitations in recruiting a sufficient sample size to achieve planned statistical power; ii) inability to account for clinical heterogeneity and assess treatment effects across a clinical spectrum; and iii) reliance on short-term, surrogate outcomes whose clinical relevance is often unclear. We mapped these challenges and associated solutions to three interrelated research paradigms: i) explanatory evidence generation; ii) comparative effectiveness/pragmatic evidence generation; and iii) patient-oriented evidence generation. Within each research paradigm, numerous criticisms and potential solutions have been described with respect to overcoming these challenges from a research study design perspective.ConclusionsOver time, discussions about clinical research for interventions for rare diseases have moved beyond methodological approaches to overcome challenges related to explanatory evidence generation, with increased recognition of the importance of pragmatic and patient-oriented evidence. Future directions for our work include developing a framework to expand current evidence synthesis practices to take into consideration many of the concepts discussed in this paper.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0851-1) contains supplementary material, which is available to authorized users.

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Orphan Therapies: Making Best Use of Postmarket Data

Cited by 4 publications

References 38 publications

Generic Substitution of Orphan Drugs for the Treatment of Rare Diseases: Exploring the Potential Challenges

Generic Substitution of Orphan Drugs for the Treatment of Rare Diseases: Exploring the Potential Challenges

Distributed Networks of Databases Analyzed Using Common Protocols and/or Common Data Models

Using a meta-narrative literature review and focus groups with key stakeholders to identify perceived challenges and solutions for generating robust evidence on the effectiveness of treatments for rare diseases

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