S. Swaroop Vedula

Outcome Reporting in Industry-Sponsored Trials of Gabapentin for Off-Label Use

BACKGROUND There is good evidence of selective outcome reporting in published reports of randomized trials. METHODS We examined reporting practices for trials of gabapentin funded by Pfizer and Warner-Lamberts subsidiary, Parke-Davis (hereafter referred to as Pfizer and Parke-Davis) for off-label indications (prophylaxis against migraine and treatment of bipolar disorders, neuropathic pain, and nociceptive pain), comparing internal company documents with published reports. RESULTS We identified 20 clinical trials for which internal documents were available from Pfizer and Parke-Davis; of these trials, 12 were reported in publications. For 8 of the 12 reported trials, the primary outcome defined in the published report differed from that described in the protocol. Sources of disagreement included the introduction of a new primary outcome (in the case of 6 trials), failure to distinguish between primary and secondary outcomes (2 trials), relegation of primary outcomes to secondary outcomes (2 trials), and failure to report one or more protocol-defined primary outcomes (5 trials). Trials that presented findings that were not significant (P > or = 0.05) for the protocol-defined primary outcome in the internal documents either were not reported in full or were reported with a changed primary outcome. The primary outcome was changed in the case of 5 of 8 published trials for which statistically significant differences favoring gabapentin were reported. Of the 21 primary outcomes described in the protocols of the published trials, 6 were not reported at all and 4 were reported as secondary outcomes. Of 28 primary outcomes described in the published reports, 12 were newly introduced. CONCLUSIONS We identified selective outcome reporting for trials of off-label use of gabapentin. This practice threatens the validity of evidence for the effectiveness of off-label interventions.

Restoring invisible and abandoned trials: a call for people to publish the findings

Unpublished and misreported studies make it difficult to determine the true value of a treatment. Peter Doshi and colleagues call for sponsors and investigators of abandoned studies to publish (or republish) and propose a system for independent publishing if sponsors fail to respond

Differences in Reporting of Analyses in Internal Company Documents Versus Published Trial Reports: Comparisons in Industry-Sponsored Trials in Off-Label Uses of Gabapentin

Using documents obtained through litigation, S. Swaroop Vedula and colleagues compared internal company documents regarding industry-sponsored trials of off-label uses of gabapentin with the published trial reports and find discrepancies in reporting of analyses.

String Motif-Based Description of Tool Motion for Detecting Skill and Gestures in Robotic Surgery

The growing availability of data from robotic and laparoscopic surgery has created new opportunities to investigate the modeling and assessment of surgical technical performance and skill. However, previously published methods for modeling and assessment have not proven to scale well to large and diverse data sets. In this paper, we describe a new approach for simultaneous detection of gestures and skill that can be generalized to different surgical tasks. It consists of two parts: (1) descriptive curve coding (DCC), which transforms the surgical tool motion trajectory into a coded string using accumulated Frenet frames, and (2) common string model (CSM), a classification model using a similarity metric computed from longest common string motifs. We apply DCC-CSM method to detect surgical gestures and skill levels in two kinematic datasets (collected from the da Vinci surgical robot). DCC-CSM method classifies gestures and skill with 87.81% and 91.12% accuracy, respectively.

Implementation of a publication strategy in the context of reporting biases. A case study based on new documents from Neurontin® litigation

BackgroundPrevious studies have documented strategies to promote off-label use of drugs using journal publications and other means. Few studies have presented internal company communications that discussed financial reasons for manipulating the scholarly record related to off-label indications. The objective of this study was to build on previous studies to illustrate implementation of a publication strategy by the drug manufacturer for four off-label uses of gabapentin (Neurontin®, Pfizer, Inc.): migraine prophylaxis, treatment of bipolar disorders, neuropathic pain, and nociceptive pain.MethodsWe included in this study internal company documents, email correspondence, memoranda, study protocols and reports that were made publicly available in 2008 as part of litigation brought by consumers and health insurers against Pfizer for fraudulent sales practices in its marketing of gabapentin (see http://pacer.mad.uscourts.gov/dc/cgi-bin/recentops.pl?filename=saris/pdf/ucl%20opinion.pdf for the Court’s findings).We reviewed documents pertaining to 20 clinical trials, 12 of which were published. We categorized our observations related to reporting biases and linked them with topics covered in internal documents, that is, deciding what should and should not be published and how to spin the study findings (re-framing study results to explain away unfavorable findings or to emphasize favorable findings); and where and when findings should be published and by whom.ResultsWe present extracts from internal company marketing assessments recommending that Pfizer and Parke-Davis (Pfizer acquired Parke-Davis in 2000) adopt a publication strategy to conduct trials and disseminate trial findings for unapproved uses rather than an indication strategy to obtain regulatory approval. We show internal company email correspondence and documents revealing how publication content was influenced and spin was applied; how the company selected where trial findings would be presented or published; how publication of study results was delayed; and the role of ghost authorship.ConclusionsTaken together, the extracts we present from internal company documents illustrate implementation of a strategy at odds with unbiased study conduct and dissemination. Our findings suggest that Pfizer and Parke-Davis’s publication strategy had the potential to distort the scientific literature, and thus misinform healthcare decision-makers.

Surgical data science for next-generation interventions

Interventional healthcare will evolve from an artisanal craft based on the individual experiences, preferences and traditions of physicians into a discipline that relies on objective decision-making on the basis of large-scale data from heterogeneous sources.Lena Maier-Hein, Swaroop Vedula, Stefanie Speidel, Nassir Navab, Ron Kikinis, Adrian Park, Matthias Eisenmann, Hubertus Feussner, Germain Forestier, Stamatia Giannarou, Makoto Hashizume, Darko Katic, Hannes Kenngott, Michael Kranzfelder, Anand Malpani, Keno März, Thomas Neumuth, Nicolas Padoy, Carla Pugh, Nicolai Schoch, Danail Stoyanov, Russell Taylor, Martin Wagner, Gregory D. Hager, Pierre Jannin

Recognizing Surgical Activities with Recurrent Neural Networks

We apply recurrent neural networks to the task of recognizing surgical activities from robot kinematics. Prior work in this area focuses on recognizing short, low-level activities, or gestures, and has been based on variants of hidden Markov models and conditional random fields. In contrast, we work on recognizing both gestures and longer, higher-level activites, or maneuvers, and we model the mapping from kinematics to gestures/maneuvers with recurrent neural networks. To our knowledge, we are the first to apply recurrent neural networks to this task. Using a single model and a single set of hyperparameters, we match state-of-the-art performance for gesture recognition and advance state-of-the-art performance for maneuver recognition, in terms of both accuracy and edit distance. Code is available at this https URL .

Cost-effectiveness of health research study participant recruitment strategies: a systematic review.

Background: A large fraction of the cost of conducting clinical trials is allocated to recruitment of participants. A synthesis of findings from studies that evaluate the cost and effectiveness of different recruitment strategies will inform investigators in designing cost-efficient clinical trials. Purpose: To systematically identify, assess, and synthesize evidence from published comparisons of the cost and yield of strategies for recruitment of participants to health research studies. Methods: We included randomized studies in which two or more strategies for recruitment of participants had been compared. We focused our economic evaluation on studies that randomized participants to different recruitment strategies. Results: We identified 10 randomized studies that compared recruitment strategies, including monetary incentives (cash or prize), direct contact (letters or telephone call), and medical referral strategies. Only two of the 10 studies compared strategies for recruiting participants to clinical trials. We found that allocating additional resources to recruit participants using monetary incentives or direct contact yielded between 4% and 23% additional participants compared to using neither strategy. For medical referral, recruitment of prostate cancer patients by nurses was cost-saving compared to recruitment by consultant urologists. For all underlying study designs, monetary incentives cost more than direct contact with potential participants, with a median incremental cost per recruitment ratio of Int

Task-Level vs. Segment-Level Quantitative Metrics for Surgical Skill Assessment

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Pairwise Comparison-Based Objective Score for Automated Skill Assessment of Segments in a Surgical Task

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