Sharing Clinical Trial Data

Lo, Bernard

doi:10.1001/jama.2015.292

Cited by 145 publications

(47 citation statements)

References 201 publications

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“…38 This effort would show the value of responsible data sharing, as detailed in a recent Institute of Medicine report. 39, 40 Finally, as variant annotations are updated, agile clinical systems would ideally make this information available in near-real time to physicians and genetic-testing laboratories. 41 Many physicians express a desire for additional guidance on genetic testing.…”

Section: Discussionmentioning

confidence: 99%

Genetic Misdiagnoses and the Potential for Health Disparities

Manrai¹,

et al. 2016

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BACKGROUND For more than a decade, risk stratification for hypertrophic cardiomyopathy has been enhanced by targeted genetic testing. Using sequencing results, clinicians routinely assess the risk of hypertrophic cardiomyopathy in a patient’s relatives and diagnose the condition in patients who have ambiguous clinical presentations. However, the benefits of genetic testing come with the risk that variants may be misclassified. METHODS Using publicly accessible exome data, we identified variants that have previously been considered causal in hypertrophic cardiomyopathy and that are overrepresented in the general population. We studied these variants in diverse populations and reevaluated their initial ascertainments in the medical literature. We reviewed patient records at a leading genetic-testing laboratory for occurrences of these variants during the near-decade-long history of the laboratory. RESULTS Multiple patients, all of whom were of African or unspecified ancestry, received positive reports, with variants misclassified as pathogenic on the basis of the understanding at the time of testing. Subsequently, all reported variants were recategorized as benign. The mutations that were most common in the general population were significantly more common among black Americans than among white Americans (P<0.001). Simulations showed that the inclusion of even small numbers of black Americans in control cohorts probably would have prevented these misclassifications. We identified methodologic shortcomings that contributed to these errors in the medical literature. CONCLUSIONS The misclassification of benign variants as pathogenic that we found in our study shows the need for sequencing the genomes of diverse populations, both in asymptomatic controls and the tested patient population. These results expand on current guidelines, which recommend the use of ancestry-matched controls to interpret variants. As additional populations of different ancestry backgrounds are sequenced, we expect variant reclassifications to increase, particularly for ancestry groups that have historically been less well studied. (Funded by the National Institutes of Health.)

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Section: Discussionmentioning

confidence: 99%

Genetic Misdiagnoses and the Potential for Health Disparities

Manrai¹,

et al. 2016

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“…Our reference standard for transparency was that all trials should be registered as per International Committee of Medical Journal Editors (ICJME) requirements, 30 31 World Health Organisation guidance, 32 33 and legislative requirements 34 ; with methods and results reported in summary form within 12 months of trial completion through online results reporting or other publication, as required under WHO guidance, 1 EU legislation, 35 36 and Food and Drug Administration Amendments Act (FDAAA) of 2007; that CSRs should be made publicly available if they have been created, in accordance with current EU legislation 36 and various calls from civic society and academia, 23 37 and that IPD should be available on request in some form to researchers. 38 39 We then operationalised these broad commitments into structured questions across the four domains of registration, methods and results sharing, CSRs, and IPD, assessing the policy commitments on each domain in detail (see web appendix 1). Prospective commitments and retrospective commitments were coded separately.…”

Section: Search Strategymentioning

confidence: 99%

Pharmaceutical companies’ policies on access to trial data, results, and methods: audit study

Goldacre

Lane

Mahtani

et al. 2017

BMJ

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“…Posjednici podataka odgovorni su za stvaranje de-identificiranih podatkovnih nizova koji štite privatnost pacijenata kroz maskiranje ili generalizaciju glavnih identifikatora. Usto, zakonski obvezujući ugovori o razmjepatients 29, 30 . Researchers are responsible for presenting the data in a format amenable for external secondary use.…”

Section: Statistička Pitanjaunclassified

“…Nedavna anketa koju je proveo britanski UK Clinical Trial Units razotkrila je neke moguće rizike vezane za razmjenu podaka 29 . Ti su se rizici u osnovi sastojali od a) zloporabe podataka, b) netočnih sekundarnih analiza, c) količine potrebnih sredstava i d) identifikacije pacijenata 29, 30 . Istraživači su odgovorni za prikazivanje podataka u tory statistical analyses 18 .…”

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