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Tingley K, Coyle D, Graham ID, et al. 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. Orphanet J Rare Dis. 2018;13(1):104doi: 10.1186/s13023-018-0851-1.
Tingley, K., Coyle, D., Graham, I. D., Sikora, L., Chakraborty, P., Wilson, K., Mitchell, J. J., Stockler-Ipsiroglu, S., Potter, B. K. (2018). 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. Orphanet journal of rare diseases, 13(1), 104. https://doi.org/10.1186/s13023-018-0851-1
Tingley, Kylie, et al. "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." Orphanet journal of rare diseases vol. 13,1 (2018): 104. doi: https://doi.org/10.1186/s13023-018-0851-1
Tingley K, Coyle D, Graham ID, Sikora L, Chakraborty P, Wilson K, Mitchell JJ, Stockler-Ipsiroglu S, Potter BK. 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. Orphanet J Rare Dis. 2018 Jun 28;13(1):104. doi: 10.1186/s13023-018-0851-1. PMID: 29954425; PMCID: PMC6022712.
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Orphanet J Rare Dis. 2018 Jun 28;13(1):104. doi: 10.1186/s13023-018-0851-1.

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.

Orphanet journal of rare diseases

Kylie Tingley, Doug Coyle, Ian D Graham, Lindsey Sikora, Pranesh Chakraborty, Kumanan Wilson, John J Mitchell, Sylvia Stockler-Ipsiroglu, Beth K Potter,

Affiliations

  1. School of Epidemiology and Public Health, University of Ottawa, 600 Peter Morand Crescent, Ottawa, ON, K1G 5Z3, Canada.
  2. Ottawa Hospital Research Institute, Ottawa, ON, Canada.
  3. Health Sciences Library, University of Ottawa, Ottawa, ON, Canada.
  4. Metabolics and Newborn Screening, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
  5. Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada.
  6. Newborn Screening Ontario, Ottawa, ON, Canada.
  7. Department of Pediatrics and Department of Medical Genetics, McGill University Health Centre, Montreal, QC, Canada.
  8. Division of Biochemical Diseases, BC Children's Hospital, Vancouver, BC, Canada.
  9. Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
  10. School of Epidemiology and Public Health, University of Ottawa, 600 Peter Morand Crescent, Ottawa, ON, K1G 5Z3, Canada. [email protected].

PMID: 29954425 PMCID: PMC6022712 DOI: 10.1186/s13023-018-0851-1

Abstract

INTRODUCTION: For 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.

METHODS: We 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.

RESULTS: Results 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.

CONCLUSIONS: Over 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.

Keywords: Comparative effectiveness; Evidence generation; Evidence synthesis; Patient-oriented outcomes; Rare diseases; Research methods

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