The Effectiveness, Safety and Costs of orphan Drugs: An Evidence-Based Review

Onakpoya, Igho; Spencer, Elizabeth A.; Thompson, Matthew; Heneghan, Carl

doi:10.1016/j.clinthera.2015.05.069

Cited by 11 publications

(13 citation statements)

References 10 publications

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“…16,30,31 However, the lack of clear standards for pediatric clinical trials apparently raises inconsistencies in the efficacy evidence required for regulatory approval, as suggested by some previous studies. [17][18][19]32,33 Mifamurtide, an orphan drug for osteosarcoma in children and young adults, is an example for which each authority made a different regulatory decision. Although the EMA approved mifamurtide in 2009 based on the results of study INT-0133, a randomized controlled phase III trial, the FDA considered the study design inappropriate and requested data from additional clinical trials.…”

Section: Articlementioning

confidence: 99%

Timing of Pediatric Drug Approval and Clinical Evidence Submitted to Regulatory Authorities: International Comparison Among Japan, the United States, and the European Union

Hirota

Yamaguchi

2020

Clin Pharma and Therapeutics

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Many prescription drugs approved for adult use lack pediatric labeling information, resulting in their off-label use in children. Drug regulatory authorities have developed legal and regulatory frameworks to promote pediatric drug development. However, the current state of pediatric indication approval and quality of efficacy evidence, which forms the basis of regulatory approvals, is unknown. Here, we analyzed novel therapeutics approved in Japan, the United States, and the European Union during 2005-2014 to investigate the timing and frequency of pediatric indication approval, and characterized the design of pediatric studies supporting regulatory approval. We found that the United States and European Union experienced a higher frequency of supplemental indication approval in pediatrics based on better-designed studies than Japan. The speed and efficiency of pediatric drug development will improve by coordinating pediatric studies on an international basis. The results also implied the necessity for a robust system of postmarketing monitoring of pediatric efficacy and safety.

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Section: Articlementioning

confidence: 99%

Timing of Pediatric Drug Approval and Clinical Evidence Submitted to Regulatory Authorities: International Comparison Among Japan, the United States, and the European Union

Hirota

Yamaguchi

2020

Clin Pharma and Therapeutics

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“…A growing number of drug development programs are targeted toward small populations, diminishing the number of patients available for clinical drug testing within a reasonable time frame. Unsurprisingly, a large fraction of recently approved drugs for rare conditions were not studied in RCTs …”

Section: What Is the Counterfactual?mentioning

confidence: 99%

“Threshold‐crossing”: A Useful Way to Establish the Counterfactual in Clinical Trials?

Eichler¹,

Bloechl-Daum

Bauer

et al. 2016

Clin Pharma and Therapeutics

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A central question in the assessment of benefit/harm of new treatments is: how does the average outcome on the new treatment (the factual) compare to the average outcome had patients received no treatment or a different treatment known to be effective (the counterfactual)? Randomized controlled trials (RCTs) are the standard for comparing the factual with the counterfactual. Recent developments necessitate and enable a new way of determining the counterfactual for some new medicines. For select situations, we propose a new framework for evidence generation, which we call “threshold‐crossing.” This framework leverages the wealth of information that is becoming available from completed RCTs and from real world data sources. Relying on formalized procedures, information gleaned from these data is used to estimate the counterfactual, enabling efficacy assessment of new drugs. We propose future (research) activities to enable “threshold‐crossing” for carefully selected products and indications in which RCTs are not feasible.

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“…Despite successes with the development of new medicines for rare diseases, orphan drug regulations have had the unintended consequence of high costs , allowing orphan drug manufacturers to profit excessively from the incentives on offer . A number of orphan drugs are not deemed to represent good value for money , even with special allowance for exceeding conventional thresholds of cost‐effectiveness .…”

Section: Introductionmentioning

confidence: 99%