BackgroundThe U.S. Food and Drug Administration traditionally has kept confidential significant amounts of information relevant to the approval or non-approval of specific drugs, devices, and biologics and about the regulatory status of such medical products in FDA’s pipeline.ObjectiveTo develop practical recommendations for FDA to improve its transparency to the public that FDA could implement by rulemaking or other regulatory processes without further congressional authorization. These recommendations would build on the work of FDA’s Transparency Task Force in 2010.MethodsIn 2016-2017, we convened (...) a team of academic faculty from Harvard Medical School, Brigham and Women’s Hospital, Yale Medical School, Yale Law School, and Johns Hopkins Bloomberg School of Public Health to develop recommendations through an iterative process of reviewing FDA’s practices, considering the legal and policy constraints on FDA in expanding transparency, and obtaining insights from independent observers of FDA.ResultsThe team developed 18 specific recommendations for improving FDA’s transparency to the public. FDA could adopt all these recommendations without further congressional action.FundingThe development of the Blueprint for Transparency at the U.S. Food and Drug Administration was funded by the Laura and John Arnold Foundation. (shrink)

BackgroundAlthough the peer review process is believed to ensure scientific rigor, enhance research quality, and improve manuscript clarity, many investigators are concerned that the process is too slow, too expensive, too unreliable, and too static. In this feasibility study, we sought to survey corresponding authors of recently published clinical research studies on the speed and efficiency of the publication process.MethodsWeb-based survey of corresponding authors of a 20% random sample of clinical research studies in MEDLINE-indexed journals with Ovid MEDLINE entry dates (...) between December 1 and 15, 2016. Survey addressed perceived manuscript importance before first submission, approximate first submission and final acceptance dates, and total number of journal submissions, external peer reviews, external peer reviewers, and revisions requested, as well as whether authors would have considered publicly sharing their manuscript on an online platform instead of submitting to a peer-reviewed journal.ResultsOf 1780 surveys distributed, 27 corresponding authors opted out or requested that we stop emailing them and 149 emails failed (e.g., emails that bounced n = 64, returned with an away from office message n = 70, or were changed/incorrect n = 15), leaving 1604 respondents, of which 337 completed the survey (21.0%). Respondents and non-respondents were similar with respect to study type and publication journals’ impact factor, although non-respondent authors had more publications (p = 0.03). Among respondents, the median impact factor of the publications’ journal was 2.7 (interquartile range (IQR), 2.0–3.6) and corresponding authors’ median h-index and number of publications was 9 (IQR, 3–20) and 27 (IQR, 10–77), respectively. The median time from first submission to journal acceptance and publication was 5 months (IQR, 3–8) and 7 months (IQR, 5–12), respectively. Most respondents (62.0%, n = 209) rated the importance of their research as a 4 or 5 (5-point scale) prior to submission. Median number of journal submissions was 1 (IQR, 1–2), external peer reviews was 1 (IQR, 1–2), external peer reviewers was 3 (IQR, 2–4), and revisions requested was 1 (IQR, 1–1). Sharing manuscripts to a public online platform, instead of submitting to a peer-reviewed journal, would have been considered by 55.2% (n = 186) of respondents.ConclusionCorresponding authors have high perceptions of their research and reported requiring few manuscript submissions prior to journal acceptance, most commonly by lower impact factor journals. (shrink)

ObjectivesTo compare changes in the number and amount of payments received by orthopedic and non-orthopedic surgeons from industry between 2014 and 2017.MethodsUsing the Centers for Medicare and Medicaid Services (CMS) Open Payment database from 2014 to 2017, we conducted a retrospective cohort study of industry payments to surgeons, including general payments and research payments.ResultsAmong orthopedic surgeons, the total number of general payments decreased from 248,698 in 2014 to 241,966 in 2017, but their total value increased from $97.1 million in 2014 (...) to $110.2 million in 2017. Among non-orthopedic surgeons, the total number decreased from 604,884 in 2014 to 582,490 in 2017, while the total value remained stable at approximately $159 million. Between 2014 and 2017, there was a differential increase in the median number of general payments received by non-orthopedic when compared to orthopedic surgeons (incidence rate ratio, 1.09; 95% CI, 1.08–1.09; p < 0.001), but a differential decline in the median value of general payments (− 8.9%; 95% CI, − 9.5%, − 8.4%; p < 0.001). Findings were consistent when stratified by nature of payment. In contrast, between 2014 and 2017, there was neither a differential change in the median number nor median value of research payments received by non-orthopedics.ConclusionExamination of a natural experiment of prior public disclosure of payments to orthopedic surgeons suggests that the Physician Payment Sunshine Act was associated with an increase in the number, but a decline in the value, of general payments received by non-orthopedic surgeons, but not on research payments received. (shrink)

BackgroundThe Freedom of Information Act (FOIA) provides access to unreleased government records that can be used to enhance the transparency and integrity of biomedical research. We characterized FOIA requests to Department of Health and Human Services (HHS) agencies, including request outcomes, processing times, backlogs, and costs.MethodsUsing HHS FOIA annual reports, we extracted data on the number of FOIA requests received and processed by HHS agencies between 2008 and 2017, as well as request outcomes. Processing times were reported in three time (...) increments, < 1–20, 21–60, or 61+ days, and trends in backlog status were also described. Information about costs and fees collected were aggregated.ResultsBetween 2008 and 2017, 69.6% of 530,094 HHS FOIA requests were received by the Centers for Medicare and Medicaid Services (CMS), 18.9% by the Food and Drug Administration (FDA), and 11.6% by all other HHS agencies. During this period, CMS processed 374,728 requests, FDA 114,938, and other HHS agencies 61,890. CMS and FDA reduced backlogged requests by 9396 (89.7%) and 4289 (65.3%), respectively, leaving backlogs of 1081 and 2279 requests at the end of 2017. CMS fully or partially granted 60.3% of requests whereas FDA fully or partially granted 72.4%. Of all requests to CMS, 82.0% were considered simple and 18.0% complex; 82.2% of simple requests and 54.9% of complex requests were processed in 20 days, and 5.6% and 29.9% were processed in 61+ days. In contrast, 60.2% of requests to FDA were considered simple and 39.8% complex; 28.8% of simple requests and 9.0% of complex requests were processed in 20 days, and 58.3% and 81.5% were processed in 61+ days. The costs to HHS associated with FOIA requests totaled $446.4 million ($809 per processed request), increasing from $28.1 million ($423 per request) in 2008 to $53.3 million ($1544 per request) in 2017. In total, HHS collected $8.5 million in fees (1.9% of total costs).ConclusionsFOIA is frequently used to obtain information about HHS and its agencies. With growing costs, minimal fees collected, and lengthy processing times, HHS agencies’ FOIA programs might be made more efficient through greater proactive record disclosure. (shrink)

Surrogate endpoints are a common application of biomarkers to estimate clinical benefit in clinical trials, despite questions about reliability. This article discusses ongoing opportunities for their validation, in the context of a regulatory environment in which they are increasingly championed.