Ethical Challenges in Biomarker‐Driven Drug Development

Hey, Spencer Phillips

doi:10.1002/cpt.862

Cited by 10 publications

(5 citation statements)

References 6 publications

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“…Better oversight about the validity and use of biomarkers in clinical trials may have helped guide resources to trials of HDL-C levels and niacin that would have contributed to evolving knowledge. 57 , 58 …”

Section: Discussionmentioning

confidence: 99%

“…Many of these trials in retrospect were unhelpful because they repeatedly retested niacin’s effect on surrogate measures, including lipid biomarkers such as HDL-C level, without formal validation that these biomarkers were clinically useful. Better oversight about the validity and use of biomarkers in clinical trials may have helped guide resources to trials of HDL-C levels and niacin that would have contributed to evolving knowledge …”

Section: Discussionmentioning

confidence: 99%

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Assessment of the Role of Niacin in Managing Cardiovascular Disease Outcomes

et al. 2019

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Key Points Question What is the evidence supporting the remaining US Food and Drug Administration–approved indications of niacin for patients with cardiovascular disease? Findings In a systematic review and meta-analysis of 119 clinical trials that included 35 760 participants, 17 trials reported niacin’s effect on cardiovascular outcomes and did not suggest that niacin prevents cardiovascular disease overall. However, a stratified meta-analysis showed that niacin as monotherapy was associated with a reduction of some cardiovascular events, a result primarily derived from 2 trials conducted in the 1970s and 1980s. Meaning Niacin may have a role as a monotherapy drug for lipid control in statin-intolerant patients, but, given substantial advancements in cardiovascular disease management since 1990, this indication should be restudied in current-day patients receiving usual baseline care.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Assessment of the Role of Niacin in Managing Cardiovascular Disease Outcomes

et al. 2019

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“…The number of drugs targeting subpopulations of specific cancers has increased over the last decade with a simultaneous increase in the number of orphan designation by the FDA for drugs indicated for cancers defined as biomarker-based subsets of more common cancers 23 29–31. However, it is interesting to note that the EMA does not follow this pattern (figure 2).…”

Section: Discussionmentioning

confidence: 99%

Application of orphan drug designation to cancer treatments (2008–2017): a comprehensive and comparative analysis of the USA and EU

Vokinger

Kesselheim

2019

BMJ Open

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ObjectiveTo determine differences in the characteristics of cancer drugs designated as orphan drugs by the Food and Drug Administration (FDA) and European Medicines Agency (EMA).Design and settingIdentification of all cancer drugs (initial or supplementary indication) with orphan status approved by the FDA between 2008–2017 based on publicly accessible reports. The European public assessment reports (EPAR) was searched to determine whether these FDA-approved drugs were also approved by the EMA.Main outcome measuresExtraction of active ingredient, trade name, approval date and approved indication from two FDA data sources (Orphan Drug Product Designation Database, Drugs@FDA) and comparison with the same data from EPAR.ResultsThe FDA approved 135 cancer drugs with orphan indications that met our inclusion criteria, of which 101 (75%) were also approved by the EMA. 80/101 (79%) were first approved in the USA. Only 41/101 (41%) also received orphan designation by the EMA. 33/101 (33%) were approved for biomarker-based indications in the USA, however, only nine approved cancer drug indications by the EMA were biomarker-derived drugs. 78% (47/60) of approved cancer drugs that were only approved in the USA with orphan status were indicated for solid tumours, 22% (13/60) had indications for non-solid tumours. By contrast, out of those approved cancer drugs that received orphan designation by both agencies, 20% (8/41) were indicated for solid, and 80% (33/41) for non-solid tumours.ConclusionsOrphan designation was intended to encourage drug development for rare conditions. This study shows that the FDA approves more cancer drugs with such designations compared with the EMA, especially for subgroups of more prevalent cancers. One reason for the difference could be that the European Union requires demonstration of significant benefit for drugs that target the same indication as a drug already on the market to earn the orphan designation.

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“…Translation and ultimately adoption into the clinic can only be accelerated if we begin to streamline clinical trial processes . Greater rates of success in clinical development will be achieved by innovation in the development of biomarkers that can predict responses, outcomes, and adverse events that advantage novel clinical trial designs . Regulatory decisions about the relative value of developing therapeutics will reflect new paradigms in assessing relative risk and benefit .…”

mentioning

confidence: 99%

“…It is noteworthy that while the pace of biomarker development is accelerating, there remain gaps in commercial incentives that drive biomarker innovation . Moreover, the growing dependence of clinical drug development programs on biomarkers has created previously unanticipated challenges in ethical frameworks surrounding human clinical trials …”

mentioning

confidence: 99%

Process Improvement for Maximized Therapeutic Innovation Outcome

Terzic

2017

Clin Pharma and Therapeutics

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Deconvoluting key biological mechanisms forms the framework for therapeutic discovery. Strategies that enable effective translation of those insights along the development and regulatory path ultimately drive validated clinical application in patients and populations. Accordingly, parity in What vs. How we transform novel mechanistic insights into therapeutic paradigms is essential in achieving success. Aligning molecular discovery with innovations in structures and processes along the discovery–development–regulation–utilization continuum maximizes the return on public and private investments for next‐generation solutions in managing health and disease.

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Ethical Challenges in Biomarker‐Driven Drug Development

Cited by 10 publications

References 6 publications

Assessment of the Role of Niacin in Managing Cardiovascular Disease Outcomes

Assessment of the Role of Niacin in Managing Cardiovascular Disease Outcomes

Application of orphan drug designation to cancer treatments (2008–2017): a comprehensive and comparative analysis of the USA and EU

Process Improvement for Maximized Therapeutic Innovation Outcome

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