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
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 wa...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-06-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-018-0851-1 |
| _version_ | 1817990701195984896 |
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| author | Kylie Tingley Doug Coyle Ian D. Graham Lindsey Sikora Pranesh Chakraborty Kumanan Wilson John J. Mitchell Sylvia Stockler-Ipsiroglu Beth K. Potter in collaboration with the Canadian Inherited Metabolic Diseases Research Network |
| author_facet | Kylie Tingley Doug Coyle Ian D. Graham Lindsey Sikora Pranesh Chakraborty Kumanan Wilson John J. Mitchell Sylvia Stockler-Ipsiroglu Beth K. Potter in collaboration with the Canadian Inherited Metabolic Diseases Research Network |
| author_sort | Kylie Tingley |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T01:02:32Z |
| format | Article |
| id | doaj.art-94b04835bd0a4e088db0ea76039580dd |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-14T01:02:32Z |
| publishDate | 2018-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-94b04835bd0a4e088db0ea76039580dd2022-12-22T02:21:21ZengBMCOrphanet Journal of Rare Diseases1750-11722018-06-0113111910.1186/s13023-018-0851-1Using 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 diseasesKylie Tingley0Doug Coyle1Ian D. Graham2Lindsey Sikora3Pranesh Chakraborty4Kumanan Wilson5John J. Mitchell6Sylvia Stockler-Ipsiroglu7Beth K. Potter8in collaboration with the Canadian Inherited Metabolic Diseases Research NetworkSchool of Epidemiology and Public Health, University of OttawaSchool of Epidemiology and Public Health, University of OttawaSchool of Epidemiology and Public Health, University of OttawaHealth Sciences Library, University of OttawaMetabolics and Newborn Screening, Department of Pediatrics, Children’s Hospital of Eastern OntarioSchool of Epidemiology and Public Health, University of OttawaDepartment of Pediatrics and Department of Medical Genetics, McGill University Health CentreDivision of Biochemical Diseases, BC Children’s HospitalSchool of Epidemiology and Public Health, University of OttawaAbstract 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.http://link.springer.com/article/10.1186/s13023-018-0851-1Rare diseasesEvidence generationComparative effectivenessPatient-oriented outcomesEvidence synthesisResearch methods |
| spellingShingle | Kylie Tingley Doug Coyle Ian D. Graham Lindsey Sikora Pranesh Chakraborty Kumanan Wilson John J. Mitchell Sylvia Stockler-Ipsiroglu Beth K. Potter in collaboration with the Canadian Inherited Metabolic Diseases Research Network 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 Rare diseases Evidence generation Comparative effectiveness Patient-oriented outcomes Evidence synthesis Research methods |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Rare diseases Evidence generation Comparative effectiveness Patient-oriented outcomes Evidence synthesis Research methods |
| url | http://link.springer.com/article/10.1186/s13023-018-0851-1 |
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