Use of real‐world evidence in regulatory decisions for rare diseases in the United States—Current status and future directions

Wu, Jun; Wang, Cunlin; Toh, Sengwee; Pisa, Federica Edith; Bauer, Larry

doi:10.1002/pds.4962

Cited by 74 publications

(62 citation statements)

References 2 publications

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“…Natural history plays a paramount role in rare disease clinical trials and drug development. The United States Food and Drug Administration recommended that in single-arm interventional trials for rare diseases, natural history studies should be used as an external control [4]. In the current study, we described the genotype distribution of a cohort of Chinese patients with DMD and their responses to GC treatment.…”

Section: Discussionmentioning

confidence: 99%

Genotype characterization and delayed loss of ambulation by glucocorticoids in a large cohort of patients with Duchenne muscular dystrophy

Zhang

Qin

et al. 2021

Orphanet J Rare Dis

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Background Duchenne muscular dystrophy (DMD) is the most common genetic muscle disease in human. We aimed to describe the genotype distribution in a large cohort of Chinese DMD patients and their delayed loss of ambulation by glucocorticoid (GC) treatments. This is to facilitate protocol designs and outcome measures for the emerging DMD clinical trials. Results A total of 1163 patients with DMD were recruited and genotyped. Genotype variations were categorized as large deletions, large duplications, and small mutations. Large deletions were further analyzed for those amenable to exon-skipping therapies. Participants aged 5 years or older were grouped into GC-treated and GC-naïve groups. Clinical progression among different genotypes and their responses to GC treatments were measured by age at loss of ambulation (LOA). Among the mutation genotypes, large deletions, large duplications, and small mutations accounted for 68.79%, 7.14%, and 24.07%, respectively. The mean age at diagnosis was 4.59 years; the median ages at LOA for the GC-naïve, prednisone/prednisolone-treated, and deflazacort-treated groups were 10.23, 12.02, and 13.95 years, respectively. The “deletion amenable to skipping exon 44” subgroup and the nonsense-mutation subgroup had older ages at LOA than the “other deletions” subgroup. Subgroups were further analyzed by both genotypes and GC status. All genotypes showed significant beneficial responses to GC treatment. Deletions amenable to skipping exon 44 showed a lower hazard ratio (0.155). The mean age at death was 18.57 years in this DMD group. Conclusion Genotype variation influences clinical progression in certain DMD groups. Beneficial responses to GC treatment were observed among all DMD genotypes. Compared with other genotypes, deletions amenable to skipping exon 44 had a lower hazard ratio, which may indicate a stronger protective effect of GC treatments on this subgroup. These data are valuable for designing future clinical trials, as clinical outcomes may be influenced by the genotypes.

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Section: Discussionmentioning

confidence: 99%

Genotype characterization and delayed loss of ambulation by glucocorticoids in a large cohort of patients with Duchenne muscular dystrophy

Zhang

Qin

et al. 2021

Orphanet J Rare Dis

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“…FDA, EMA, and NMPA have established databases, data sharing platforms and structured data quality standards to ensure the production of high-quality RWD. FDA, EMA, and Health Canada have developed frameworks and programs to promote the use of highquality RWD and to support the identification of opportunities where RWE can enhance clinical trials by overcoming clinical trial limitations (18,59). In terms of informing regulatorydecision, EMA has cooperated with FDA and Japan regulatory partners on orphan drug supervision.…”

Section: Discussionmentioning

confidence: 99%

Integrating Real-World Evidence in the Regulatory Decision-Making Process: A Systematic Analysis of Experiences in the US, EU, and China Using a Logic Model

Chen

Lai

et al. 2021

Front. Med.

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Real world evidence (RWE) and real-world data (RWD) are drawing ever-increasing attention in the pharmaceutical industry and drug regulatory authorities (DRAs) all over the world due to their paramount role in supporting drug development and regulatory decision making. However, there is little systematic documentary analysis about how RWE was integrated for the use by the DRAs in evaluating new treatment approaches and monitoring post-market safety. This study aimed to analyze and discuss the integration of RWE into regulatory decision-making process from the perspective of DRAs. Different development strategies to develop and adopt RWE by the DRAs in the US, Europe, and China were reviewed and compared, and the challenges encountered were discussed. It was found that different strategies on development of RWE were applied by FDA, EMA, and NMPA. The extent to which RWE was adopted in China was relatively limited compared to that in the US and EU, which was highly related to the national pharmaceutical environment and development stages. A better understanding of the overall goals, inputs, activities, outputs, and outcomes in developing RWE will help inform actions to harness RWD and leverage RWE for better health care decisions.

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“…8 Similarly, a more recent international review of the use of RWD for new drug applications and additional indications found that they have so far mostly concentrated on rare diseases in oncology and metabolism, such as for the approval of cerliponase alfa, asfotase alfa, and uridine triacetate. 3 , 9 However, in order to improve efficient patient access to therapies, global regulators such as FDA are now examining how to optimize the incorporation of RWE across the drug life cycle. 1 , 4…”

Section: Why Is Real-world Evidence Important For Pharmacists?mentioning

confidence: 99%

Old dog with new tricks: An introduction to real-world evidence for pharmacists

Rahmatian

Tadrous

2021

American Journal of Health-System Pharmacy

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Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

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Use of real‐world evidence in regulatory decisions for rare diseases in the United States—Current status and future directions

Cited by 74 publications

References 2 publications

Genotype characterization and delayed loss of ambulation by glucocorticoids in a large cohort of patients with Duchenne muscular dystrophy

Genotype characterization and delayed loss of ambulation by glucocorticoids in a large cohort of patients with Duchenne muscular dystrophy

Integrating Real-World Evidence in the Regulatory Decision-Making Process: A Systematic Analysis of Experiences in the US, EU, and China Using a Logic Model

Old dog with new tricks: An introduction to real-world evidence for pharmacists

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