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Orphan therapies: making best use of postmarket data.

ABSTRACT: BACKGROUND: Postmarket surveillance of the comparative safety and efficacy of orphan therapeutics is challenging, particularly when multiple therapeutics are licensed for the same orphan indication. To make best use of product-specific registry data collected to fulfill regulatory requirements, we propose the creation of a distributed electronic health data network among registries. Such a network could support sequential statistical analyses designed to detect early warnings of excess risks. We use a simulated example to explore the circumstances under which a distributed network may prove advantageous. METHODS: We perform sample size calculations for sequential and non-sequential statistical studies aimed at comparing the incidence of hepatotoxicity following initiation of two newly licensed therapies for homozygous familial hypercholesterolemia. We calculate the sample size savings ratio, or the proportion of sample size saved if one conducted a sequential study as compared to a non-sequential study. Then, using models to describe the adoption and utilization of these therapies, we simulate when these sample sizes are attainable in calendar years. We then calculate the analytic calendar time savings ratio, analogous to the sample size savings ratio. We repeat these analyses for numerous scenarios. KEY RESULTS: Sequential analyses detect effect sizes earlier or at the same time as non-sequential analyses. The most substantial potential savings occur when the market share is more imbalanced (i.e., 90% for therapy A) and the effect size is closest to the null hypothesis. However, due to low exposure prevalence, these savings are difficult to realize within the 30-year time frame of this simulation for scenarios in which the outcome of interest occurs at or more frequently than one event/100 person-years. CONCLUSIONS: We illustrate a process to assess whether sequential statistical analyses of registry data performed via distributed networks may prove a worthwhile infrastructure investment for pharmacovigilance.

SUBMITTER: Maro JC

PROVIDER: S-EPMC4124121 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Orphan therapies: making best use of postmarket data.

Maro Judith C JC Brown Jeffrey S JS Dal Pan Gerald J GJ Li Lingling L

Journal of general internal medicine 20140801

<h4>Background</h4>Postmarket surveillance of the comparative safety and efficacy of orphan therapeutics is challenging, particularly when multiple therapeutics are licensed for the same orphan indication. To make best use of product-specific registry data collected to fulfill regulatory requirements, we propose the creation of a distributed electronic health data network among registries. Such a network could support sequential statistical analyses designed to detect early warnings of excess ri ...[more]

PMID: 25029972

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Project description:Orphan crops are indigenous and invariably grown by small and marginal farmers under subsistence farming systems. These crops, which are common and widely accepted by local farmers, are highly rich in nutritional profile, good for medicinal purposes, and well adapted to suboptimal growing conditions. However, these crops have suffered neglect and abandonment from the scientific community because of very low or no investments in research and genetic improvement. A plausible reason for this is that these crops are not traded internationally at a rate comparable to that of the major food crops such as wheat, rice, and maize. Furthermore, marginal environments have poor soils and are characterized by extreme weather conditions such as heat, erratic rainfall, water deficit, and soil and water salinity, among others. With more frequent extreme climatic events and continued land degradation, orphan crops are beginning to receive renewed attention as alternative crops for dietary diversification in marginal environments and, by extension, across the globe. Increased awareness of good health is also a major contributor to the revived attention accorded to orphan crops. Thus, the introduction, evaluation, and adaptation of outstanding varieties of orphan crops for dietary diversification will contribute not only to sustained food production but also to improved nutrition in marginal environments. In this review article, the concept of orphan crops vis-à-vis marginality and food and nutritional security is defined for a few orphan crops. We also examined recent advances in research involving orphan crops and the potential of these crops for dietary diversification within the context of harsh marginal environments. Recent advances in genomics coupled with molecular breeding will play a pivotal role in improving the genetic potential of orphan crops and help in developing sustainable food systems. We concluded by presenting a potential roadmap to future research engagement and a policy framework with recommendations aimed at facilitating and enhancing the adoption and sustainable production of orphan crops under agriculturally marginal conditions.

Project description:BackgroundBest interests is a ubiquitous principle in medical policy and practice, informing the treatment of both children and adults. Yet theory underlying the concept of best interests is unclear and rarely articulated. This paper examines bioethical literature for theoretical accounts of best interests to gain a better sense of the meanings and underlying philosophy that structure understandings.MethodsA scoping review of was undertaken. Following a literature search, 57 sources were selected and analysed using the thematic method.ResultsThree themes emerged. The first placed best interests within the structure of wider theory, noting relationships with consequentialism, deontology, prudential value theory, rights and political philosophy. The second mapped a typology of processes of decision-making, among which best interests was ambiguously positioned. It further indicated factors that informed best interests decision-making, primarily preferences, dignity and quality of life. The final theme considered best interests from a relational perspective.ConclusionsCharacterisation of best interests as strictly paternalist and consequentialist is questionable: while accounts often suggested a consequentialist basis for best interests, arguments appeared philosophically weak. Deontological accounts, found in law and Kantianism, and theories of political liberalism influenced accounts of best interests, with accounts often associating best interests with negative patient preferences (i.e. individual refusals). There was much more emphasis on negative interests than positive interests. Besides preference, factors like dignity and quality of life were held to inform best interests decisions, but generally were weakly defined. To the extent that preferences were unable to inform decision making, decisions were either made by proxy authority or by an intersubjective process of diffuse authority. Differing approaches reflect bifurcations in liberal philosophy between new liberalism and neo-liberalism. Although neither account of authority appears dominant, bias to negative interests suggests that bioethical debate tends to reflect the widespread ascendancy of neo-liberalism. This attitude was underscored by the way relational accounts converged on private familial authority. The visible connections to theory suggest that best interests is underpinned by socio-political trends that may set up frictions with practice. How practice negotiates these frictions remains a key question.

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Orphan therapies: making best use of postmarket data.

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Orphan therapies: making best use of postmarket data.

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