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Brittany C Tsou,1 Kerry Smith,1 Rahul Shah,1 Fasika A Woreta,1 S Swaroop Vedula,2 Shameema Sikder1 1Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Malone Center for Engineering in Healthcare, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USACorrespondence: Shameema Sikder, Wilmer Eye Institute, Johns Hopkins University School of Medicine, 600 N Wolfe St, Baltimore, MD, 21218, USA, Tel +1-240-482-1108, Email ssikder1@jhmi.eduPurpose: To estimate the opportunity cost to attending surgeons of teaching residents cataract surgery in the operating room.Patients and methods: Operating room records at an academic teaching hospital from July 2016 to July 2020 were analyzed in this retrospective review of cases. Cases were identified using Current Procedural Terminology (CPT) codes 66982 and 66984 for cataract surgery. Outcomes measured include operative time and work relative value units (wRVUs). Cost analysis was performed using the generic 2021 Medicare Conversion Factor.Results: Of 8813 cases, 2906 (33.0%) included resident involvement. For CPT 66982 cases, median (interquartile range (IQR)) operative time was 47 (22) minutes with resident involvement and 28 (18) minutes without (p< 0.001). For CPT 66984 cases, median (IQR) operative time was 34 (15) minutes with resident involvement and 20 (11) minutes without (p< 0.001). Median wRVUs was 78.5 (20.9) with resident involvement and 61.0 (14.4) without (p< 0.001) which converted to an opportunity cost (IQR) per case of &dollar;1393.72 (&dollar;1055.63). Among cases involving residents, median operative time was significantly higher during the first and second quarters (p< 0.001) and for every quarter when compared to cases performed by attendings only (p< 0.001).Conclusion: Teaching cataract surgery in the operating room is associated with a considerable opportunity cost for attending surgeons.Keywords: cataract surgery, resident involvement, opportunity cost, relative value units

BACKGROUND: Ophthalmia neonatorum is an infection of the eyes in newborns that can lead to blindness, particularly if the infection is caused by Neisseria gonorrhoeae. Antiseptic or antibiotic medication is dispensed into the eyes of newborns, or dispensed systemically, soon after delivery to prevent neonatal conjunctivitis and potential vision impairment. OBJECTIVES: 1. To determine if any type of systemic or topical eye medication is better than placebo or no prophylaxis in preventing ophthalmia neonatorum. 2. To determine if any one systemic or topical eye medication is better than any other medication in preventing ophthalmia neonatorum. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, and three trials registers, date of last search 4 October 2019. We also searched references of included studies and contacted pharmaceutical companies. SELECTION CRITERIA: We included randomised and quasi‐randomised controlled trials of any topical, systemic, or combination medical interventions used to prevent ophthalmia neonatorum in newborns compared with placebo, no prophylaxis, or with each other. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. Outcomes were: blindness or any adverse visual outcome at 12 months, conjunctivitis at 1 month (gonococcal (GC), chlamydial (CC), bacterial (BC), any aetiology (ACAE), or unknown aetiology (CUE)), and adverse effects. MAIN RESULTS: We included 30 trials with a total of 79,198 neonates. Eighteen studies were conducted in high‐income settings (the USA, Europe, Israel, Canada), and 12 were conducted in low‐ and middle‐income settings (Africa, Iran, China, Indonesia, Mexico). Fifteen of the 30 studies were quasi‐randomised. We judged every study to be at high risk of bias in at least one domain. Ten studies included a comparison arm with no prophylaxis. There were 14 different prophylactic regimens and 12 different medications in the 30 included studies. Any prophylaxis compared to no prophylaxis Unless otherwise indicated, the following evidence comes from studies assessing one or more of the following interventions: tetracycline 1%, erythromycin 0.5%, povidone‐iodine 2.5%, silver nitrate 1%. None of the studies reported data on the primary outcomes: blindness or any adverse visual outcome at any time point. There was only very low‐certainty evidence on the risk of GC with prophylaxis (4/5340 newborns) compared to no prophylaxis (5/2889) at one month (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.24 to 2.65, 3 studies). Low‐certainty evidence suggested there may be little or no difference in effect on CC (RR 0.96, 95% CI 0.57 to 1.61, 4874 newborns, 2 studies) and BC (RR 0.84, 95% CI 0.37 to 1.93, 3685 newborns, 2 studies). Moderate‐certainty evidence suggested a probable reduction in risk of ACAE at one month (RR 0.65, 95% 0.54 to 0.78, 9666 newborns, 8 studies assessing tetracycline 1%, erythromycin 0.5%, povidone‐iodine 2.5%, silver nitrate 1%, colostrum, bacitracin‐phenacaine ointment). There was only very low‐certainty evidence on CUE (RR 1.75, 95% CI 0.37 to 8.28, 330 newborns, 1 study). Very low‐certainty evidence on adverse effects suggested no increased nasolacrimal duct obstruction (RR 0.93, 95% CI 0.68 to 1.28, 404 newborns, 1 study of erythromycin 0.5% and silver nitrate 1%) and no increased keratitis (single study of 40 newborns assessing silver nitrate 1% with no events). Any prophylaxis compared to another prophylaxis Overall, evidence comparing different interventions did not suggest any consistently superior intervention. However, most of this evidence was of low‐certainty and was extremely limited. AUTHORS' CONCLUSIONS: There are no data on whether prophylaxis for ophthalmia neonatorum prevents serious outcomes such as blindness or any adverse visual outcome. Moderate‐certainty evidence suggests that the use of prophylaxis may lead to a reduction in the incidence of ACAE in newborns but the evidence for effect on GC, CC or BC was less certain. Comparison of individual interventions did not suggest any consistently superior intervention, but data were limited. A trial comparing tetracycline, povidone‐iodine (single administration), and chloramphenicol for GC and CC could potentially provide the community with an effective, universally applicable prophylaxis against ophthalmia neonatorum.

Stimulus deprivation amblyopia (SDA) develops due to an obstruction to the passage of light secondary to a condition such as cataract. The obstruction prevents formation of a clear image on the retina. SDA can be resistant to treatment, leading to poor visual prognosis. SDA probably constitutes less than 3% of all amblyopia cases, although precise estimates of prevalence are unknown. In developed countries, most patients present under the age of one year; in less developed parts of the world patients are likely to be older at the time of presentation. The mainstay of treatment is removal of the cataract and then occlusion of the better-seeing eye, but regimens vary, can be difficult to execute, and traditionally are believed to lead to disappointing results.Our objective was to evaluate the effectiveness of occlusion therapy for SDA in an attempt to establish realistic treatment outcomes. Where data were available, we also planned to examine evidence of any dose response effect and to assess the effect of the duration, severity, and causative factor on the size and direction of the treatment effect.We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2013), EMBASE (January 1980 to October 2013), the Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2013), PubMed (January 1946 to October 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com ), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 October 2013.We planned to include randomized and quasi-randomized controlled trials of participants with unilateral SDA with visual acuity worse than 0.2 LogMAR or equivalent. We did not specify any restrictions for inclusion based upon age, gender, ethnicity, co-morbidities, medication use, or the number of participants.Two review authors independently assessed study abstracts identified by the electronic searches.We did not identify any trials that met the inclusion criteria specified in the protocol for this review.We found no evidence on the effectiveness of any treatment for SDA. Future randomized controlled trials are needed in order to evaluate the safety and effectiveness of occlusion, duration of treatment, level of vision that can be realistically achieved, effects of age at onset and magnitude of visual defect, optimum occlusion regimen, and factors associated with satisfactory and unsatisfactory outcomes with the use of various interventions for SDA.

Lumbar spine surgery suffers from high variability in patient outcomes,1–9 heterogeneous treatment patterns, and a high frequency of undesirable outcomes, such as revision surgery,8 failed back surgery,7 and recurrent lumbar disk herniations.10 This heterogeneity could be attributed to variable patient characteristics, surgeon preferences, hospital and surgeon volume, and complexity of the intervention.11–13 However, current understanding of the contributing factors that determine the outcome variability remains ambiguous and underexplored.14–16 In this context, models to predict patient outcomes provide a valuable resource for patient selection, treatment optimization, and rehabilitative pathway design.11,17–19 Previous studies that investigated variability in pain and functional outcomes were limited to analyzing patient demographic and preoperative clinical characteristics as the underlying factors.11,12,19 While such factors [e.g., age, body mass index (BMI), and smoking status] partially contribute to the outcome variability, additional surgery-specific features could further illuminate and improve the utility of prediction models. Some studies have tended toward development of increasingly complex modeling techniques (e.g., deep neural networks14,20) to improve accuracy, particularly for scenarios in which the predictor variables arise from a limited number of available preoperative characteristics (i.e., demographic data). In spite of devising complex machine learning algorithms, model generalizability is challenging to achieve with a limited set of predictor variables that may not fully explain the variability in clinical outcomes. Even though advanced learning methods perform better under conditions of sparse data and/or limited input variables, increasingly complex models also introduce challenges to explainability in the predictions and the ability to identify actionable features. A large number of images are routinely acquired for perioperative diagnostic and therapeutic evaluation purposes before, during, and after spine surgery. These images play a vital role in diagnosing spinal pathology, determining surgery indications, ensuring safe intervention via intraoperative guidance, and assessing the surgical product in postoperative and follow-up visits. Such images capture distinctive features related to anatomy, pathology, and the changes effected during surgery. In fact, qualitative radiological assessment has been an important basis for outcome measurement prior to (or complementary to) patient-reported outcomes (PROs). Thus, incorporating automatically derived image features in addition to previously investigated patient characteristics could improve the accuracy and utility of prediction models. Consequently, several studies have evaluated the relationship between individual measures manually obtained from images and patient outcomes in lumbar, thoracic, and cervical spine surgery. Example measures include Modic changes,21,22 signal intensity-based metrics,23–25 and the lowest instrumented vertebra take-off angle.26,27 In contrast to manually obtained features, recent advances facilitate the automatic extraction of several anatomical features from spine imaging.28–31 Example image-based features include automatic labeling of vertebral levels, global spinal alignment, endplate angles, intervertebral space, number of levels treated, and measurements of surgical instrumentation. To our knowledge, there are no previous studies evaluating statistical models to predict patient outcomes in lumbar spine surgery that use automatically derived quantitative measurements from radiological images. The objective of this study was to develop and validate a data-analytic framework referred to as “SpineCloud,” which includes quantitative features automatically derived from spine imaging in addition to patient demographic and clinical characteristics to predict function and pain improvement after lumbar spine surgery. A learning algorithm was trained and validated to make predictions by combining disparate features based on demographics and image analytics. In this work, we used a boosted decision tree algorithm that inherently handles ordinal and continuous variables in a common predictor variable space. The prediction task was modeled as a binary classification to estimate functional improvement or nonimprovement at 3- and 12-month intervals after surgery.

This paper introduces Surgical Data Science as an emerging scientific discipline. Key perspectives are based on discussions during an intensive two-day international interactive workshop that brought together leading researchers working in the related field of computer and robot assisted interventions. Our consensus opinion is that increasing access to large amounts of complex data, at scale, throughout the patient care process, complemented by advances in data science and machine learning techniques, has set the stage for a new generation of analytics that will support decision-making and quality improvement in interventional medicine. In this article, we provide a consensus definition for Surgical Data Science, identify associated challenges and opportunities and provide a roadmap for advancing the field.

Background Aqueous shunts are employed to control intraocular pressure (IOP) for people with primary or secondary glaucomas who fail or are not candidates for standard surgery. Objectives To assess the effectiveness and safety of aqueous shunts for reducing IOP in glaucoma compared with standard surgery, another type of aqueous shunt, or modification to the aqueous shunt procedure. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 8), MEDLINE Ovid (1946 to August 2016), Embase.com (1947 to August 2016), PubMed (1948 to August 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to August 2016), ClinicalTrials.gov (www.clinicaltrials.gov); searched 15 August 2016, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 15 August 2016. We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 15 August 2016. We also searched the reference lists of identified trial reports and the Science Citation Index to find additional trials. Selection criteria We included randomized controlled trials that compared various types of aqueous shunts with standard surgery or to each other in eyes with glaucoma. Data collection and analysis Two review authors independently screened search results for eligibility, assessed the risk of bias, and extracted data from included trials. We contacted trial investigators when data were unclear or not reported. We graded the certainty of the evidence using the GRADE approach. We followed standard methods as recommended by Cochrane. Main results We included 27 trials with a total of 2099 participants with mixed diagnoses and comparisons of interventions. Seventeen studies reported adequate methods of randomization, and seven reported adequate allocation concealment. Data collection and follow-up times varied. Four trials compared an aqueous shunt (Ahmed or Baerveldt) with trabeculectomy, of which three reported one-year outcomes. At one-year, the difference in IOP between aqueous shunt groups and trabeculectomy groups was uncertain (mean difference (MD) 2.55 mmHg, 95% confidence interval (CI) -0.78 to 5.87; 380 participants; very low-certainty evidence). The difference in logMAR visual acuity was also uncertain (MD 0.12 units, 95% CI -0.07 to 0.31; 380 participants; very low-certainty evidence). In two trials, the difference in visual field score was uncertain (MD -0.25, 95% CI -1.91 to 1.40; 196 participants; very low-certainty evidence). The mean number of antiglaucoma medications was higher in the aqueous shunt group than the trabeculectomy group in one trial (MD 0.80, 95% CI 0.48 to 1.12; 184 participants; low-certainty evidence). The effect on needing additional glaucoma surgery was uncertain between groups in two trials (risk ratio (RR) 0.24, 95% CI 0.04 to 1.36; 329 participants; very low-certainty evidence). In one trial, fewer total adverse events were reported in the aqueous shunt group than the trabeculectomy group (RR 0.59, 95% CI 0.43 to 0.81; 212 participants; very low-certainty evidence). No trial reported quality-of-life outcomes at one-year follow-up. Two trials that compared the Ahmed implant with the Baerveldt implant for glaucoma found higher mean IOP in the Ahmed group at one-year follow-up (MD 2.60 mmHg, 95% CI 1.58 to 3.62; 464 participants; moderate-certainty evidence). The difference in logMAR visual acuity was uncertain between groups (MD -0.07 units, 95% CI -0.27 to 0.13; 501 participants; low-certainty evidence). The MD in number of antiglaucoma medications was within one between groups (MD 0.35, 95% CI 0.11 to 0.59; 464 participants; moderate-certainty evidence). More participants in the Ahmed group required additional glaucoma surgery than the Baerveldt group (RR 2.77, 95% CI 1.02 to 7.54; 514 participants; moderate-certainty evidence). The two trials reported specific adverse events but not overall number of adverse events. Neither trial reported visual field or quality-of-life outcomes at one-year follow-up. One trial compared the Ahmed implant with the Molteno implant for glaucoma over two-year follow-up. Mean IOP was higher in the Ahmed group than the Molteno group (MD 1.64 mmHg, 95% CI 0.85 to 2.43; 57 participants; low-certainty evidence). The differences in logMAR visual acuity (MD 0.08 units, 95% CI -0.24 to 0.40; 57 participants; very low-certainty evidence) and mean deviation in visual field (MD -0.18 dB, 95% CI -3.13 to 2.77; 57 participants; very low-certainty evidence) were uncertain between groups. The mean number of antiglaucoma medications was also uncertain between groups (MD -0.38, 95% CI -1.03 to 0.27; 57 participants; low-certainty evidence). The trial did not report the proportion needing additional glaucoma surgery, total adverse events, or quality-of-life outcomes. Two trials compared the double-plate Molteno implant with the Schocket shunt for glaucoma; one trial reported outcomes only at six-month follow-up, and the other did not specify the follow-up time. At six-months, mean IOP was lower in the Molteno group than the Schocket group (MD -2.50 mmHg, 95% CI -4.60 to -0.40; 115 participants; low-certainty evidence). Neither trial reported the proportion needing additional glaucoma surgery, total adverse events, or visual acuity, visual field, or quality-of-life outcomes. The remaining 18 trials evaluated modifications to aqueous shunts, including 14 trials of Ahmed implants (early aqueous suppression versus standard medication regimen, 2 trials; anti-vascular endothelial growth factor agent versus none, 4 trials; corticosteroids versus none, 2 trials; shunt augmentation versus none, 3 trials; partial tube ligation versus none, 1 trial; pars plana implantation versus conventional implantation, 1 trial; and model M4 versus model S2,1 trial); 1 trial of 500 mm2 Baerveldt versus 350 mm2 Baerveldt; and 3 trials of Molteno implants (single-plate with oral corticosteroids versus single-plate without oral corticosteroids, 1 trial; double-plate versus single-plate, 1 trial; and pressure-ridge versus double-plate with tube ligation, 1 trial). Authors' conclusions Information was insufficient to conclude whether there are differences between aqueous shunts and trabeculectomy for glaucoma treatment. While the Baerveldt implant may lower IOP more than the Ahmed implant, the evidence was of moderate-certainty and it is unclear whether the difference in IOP reduction is clinically significant. Overall, methodology and data quality among existing randomized controlled trials of aqueous shunts was heterogeneous across studies, and there are no well-justified or widely accepted generalizations about the superiority of one surgical procedure or device over another.

Training skillful and competent surgeons is critical to ensure high quality of care and to minimize disparities in access to effective care. Traditional models to train surgeons are being challenged by rapid advances in technology, an intensified patient-safety culture, and a need for value-driven health systems. Simultaneously, technological developments are enabling capture and analysis of large amounts of complex surgical data. These developments are motivating a “surgical data science” approach to objective computer-aided technical skill evaluation (OCASE-T) for scalable, accurate assessment; individualized feedback; and automated coaching. We define the problem space for OCASE-T and summarize 45 publications representing recent research in this domain. We find that most studies on OCASE-T are simulation based; very few are in the operating room. The algorithms and validation methodologies used for OCASE-T are highly varied; there is no uniform consensus. Future research should emphasize competency assessment in the operating room, validation against patient outcomes, and effectiveness for surgical training.

Ocular infestation with Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea and consequently lead to complications such as glaucoma, cataract, and posterior synechiae.The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids for ocular toxoplasmosis.We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to October 2012), EMBASE (January 1980 to October 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We searched the reference lists of included studies for any additional studies not identified by the electronic searches. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 October 2012.We planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with active ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, or different doses or times of initiation of corticosteroids.Two authors independently screened titles and abstracts retrieved from the electronic searches. We retrieved full-text articles of studies categorized as 'unsure' or 'include' after review of the abstracts. Two authors independently reviewed each full-text article. Discrepancies were resolved through discussion.The electronic searches retrieved 368 titles and abstracts. We reviewed 20 full-text articles. We identified no trials eligible for inclusion in this systematic review.Although research has identified wide variation in practices regarding use of corticosteroids, our systematic review did not identify evidence from randomized controlled trials for the role of corticosteroids in the management of ocular toxoplasmosis. Several questions remain unanswered by well-conducted randomized trials in this context, including whether use of corticosteroids is more effective than use of anti-parasitic therapy alone, when corticosteroids should be initiated in the treatment regimen (early versus late course of treatment), and which dosage and duration of steroid use is best. These questions are easily amenable to research using a randomized controlled design and they are ethical due to the absence of evidence to support or discourage use of corticosteroids for this condition. The question of foremost importance, however, is whether they should be used as adjunct therapy (that is, additional) to anti-parasitic agents.

Background Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent development and progression of the ocular complications of diabetes. Simultaneous blood pressure control has been advocated for the same purpose, but findings reported from individual studies have supported varying conclusions regarding the ocular benefit of interventions on blood pressure. Objectives The primary aim of this review was to summarize the existing evidence regarding the effect of interventions to control or reduce blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs. A secondary aim was to compare classes of anti-hypertensive medications with respect to the same outcomes. Search methods We searched a number of electronic databases including CENTRAL as well as ongoing trial registries. We last searched the electronic databases on 25 April 2014. We also reviewed reference lists of review articles and trial reports selected for inclusion. In addition, we contacted investigators of trials with potentially pertinent data. Selection criteria We included in this review randomized controlled trials (RCTs) in which either type 1 or type 2 diabetic participants, with or without hypertension, were assigned randomly to intense versus less intense blood pressure control, to blood pressure control versus usual care or no intervention on blood pressure, or to different classes of anti-hypertensive agents versus placebo. Data collection and analysis Pairs of review authors independently reviewed titles and abstracts from electronic and manual searches and the full text of any document that appeared to be relevant. We assessed included trials independently for risk of bias with respect to outcomes reported in this review. We extracted data regarding trial characteristics, incidence and progression of retinopathy, visual acuity, quality of life, and cost-effectiveness at annual intervals after study entry whenever provided in published reports and other documents available from included trials. Main results We included 15 RCTs, conducted primarily in North America and Europe, that had enrolled 4157 type 1 and 9512 type 2 diabetic participants, ranging from 16 to 2130 participants in individual trials. In 10 of the 15 RCTs, one group of participants was assigned to one or more anti-hypertensive agents and the control group received placebo. In three trials, intense blood pressure control was compared to less intense blood pressure control. In the remaining two trials, blood pressure control was compared with usual care. Five of the 15 trials enrolled type 1 diabetics, and 10 trials enrolled type 2 diabetics. Six trials were sponsored entirely by pharmaceutical companies, seven trials received partial support from pharmaceutical companies, and two studies received support from government-sponsored grants and institutional support. Study designs, populations, interventions, and lengths of follow-up (range one to nine years) varied among the included trials. Overall, the quality of the evidence for individual outcomes was low to moderate. For the primary outcomes, incidence and progression of retinopathy, the quality of evidence was downgraded due to inconsistency and imprecision of estimates from individual studies and differing characteristics of participants. For primary outcomes among type 1 diabetics, one of the five trials reported incidence of retinopathy and one trial reported progression of retinopathy after 4 to 5 years of treatment and follow-up; four of the five trials reported a combined outcome of incidence and progression over the same time interval. Among type 2 diabetics, 5 of the 10 trials reported incidence of diabetic retinopathy and 3 trials reported progression of retinopathy; one of the 10 trials reported a combined outcome of incidence and progression during a 4- to 5-year follow-up period. One trial in which type 2 diabetics participated had reported no primary (or secondary) outcome targeted for this review. The evidence from these trials supported a benefit of more intensive blood pressure control intervention with respect to 4- to 5-year incidence of diabetic retinopathy (estimated risk ratio (RR) 0.80; 95% confidence interval (CI) 0.71 to 0.92) and the combined outcome of incidence and progression (estimated RR 0.78; 95% CI 0.63 to 0.97). The available evidence provided less support for a benefit with respect to 4- to 5-year progression of diabetic retinopathy (point estimate was closer to 1 than point estimates for incidence and combined incidence and progression, and the CI overlapped 1; estimated RR 0.88; 95% CI 0.73 to 1.05). The available evidence regarding progression to proliferative diabetic retinopathy or clinically significant macular edema or moderate to severe loss of best-corrected visual acuity did not support a benefit of intervention on blood pressure: estimated RRs and 95% CIs 0.95 (0.83 to 1.09) and 1.06 (0.85 to 1.33), respectively, after 4 to 5 years of follow-up. Findings within subgroups of trial participants (type 1 and type 2 diabetics; participants with normal blood pressure levels at baseline and those with elevated levels) were similar to overall findings. The adverse event reported most often (7 of 15 trials) was death, yielding an estimated RR 0.86 (95% CI 0.64 to 1.14). Hypotension was reported from three trials; the estimated RR was 2.08 (95% CI 1.68 to 2.57). Other adverse ocular events were reported from single trials. Authors' conclusions Hypertension is a well-known risk factor for several chronic conditions in which lowering blood pressure has proven to be beneficial. The available evidence supports a beneficial effect of intervention to reduce blood pressure with respect to preventing diabetic retinopathy for up to 4 to 5 years. However, the lack of evidence to support such intervention to slow progression of diabetic retinopathy or to prevent other outcomes considered in this review, along with the relatively modest support for the beneficial effect on incidence, weakens the conclusion regarding an overall benefit of intervening on blood pressure solely to prevent diabetic retinopathy.

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., Background Details about the type of analysis (e.g., intent to treat [ITT]) and definitions (i.e., criteria for including participants in the analysis) are necessary for interpreting a clinical trial's findings. Our objective was to compare the description of types of analyses and criteria for including participants in the publication (i.e., what was reported) with descriptions in the corresponding internal company documents (i.e., what was planned and what was done). Trials were for off-label uses of gabapentin sponsored by Pfizer and Parke-Davis, and documents were obtained through litigation. Methods and Findings For each trial, we compared internal company documents (protocols, statistical analysis plans, and research reports, all unpublished), with publications. One author extracted data and another verified, with a third person verifying discordant items and a sample of the rest. Extracted data included the number of participants randomized and analyzed for efficacy, and types of analyses for efficacy and safety and their definitions (i.e., criteria for including participants in each type of analysis). We identified 21 trials, 11 of which were published randomized controlled trials, and that provided the documents needed for planned comparisons. For three trials, there was disagreement on the number of randomized participants between the research report and publication. Seven types of efficacy analyses were described in the protocols, statistical analysis plans, and publications, including ITT and six others. The protocol or publication described ITT using six different definitions, resulting in frequent disagreements between the two documents (i.e., different numbers of participants were included in the analyses). Conclusions Descriptions of analyses conducted did not agree between internal company documents and what was publicly reported. Internal company documents provide extensive documentation of methods planned and used, and trial findings, and should be publicly accessible. Reporting standards for randomized controlled trials should recommend transparent descriptions and definitions of analyses performed and which study participants are excluded. Please see later in the article for the Editors' Summary, Editors' Summary Background To be credible, published research must present an unbiased, transparent, and accurate description of the study methods and findings so that readers can assess all relevant information to make informed decisions about the impact of any conclusions. Therefore, research publications should conform to universally adopted guidelines and checklists. Studies to establish whether a treatment is effective, termed randomized controlled trials (RCTs), are checked against a comprehensive set of guidelines: The robustness of trial protocols are measured through the Standard Protocol Items for Randomized Trials (SPIRIT), and the Consolidated Standards of Reporting Trials (CONSORT) statement (which was constructed and agreed by a meeting of journal editors in 1996, and has been updated over the years) includes a 25-point checklist that covers all of the key points in reporting RCTs. Why Was This Study Done? Although the CONSORT statement has helped improve transparency in the reporting of the methods and findings from RCTs, the statement does not define how certain types of analyses should be conducted and which patients should be included in the analyses, for example, in an intention-to-treat analysis (in which all participants are included in the data analysis of the group to which they were assigned, whether or not they completed the intervention given to the group). So in this study, the researchers used internal company documents released in the course of litigation against the pharmaceutical company Pfizer regarding the drug gabapentin, to compare between the internal and published reports the reporting of the numbers of participants, the description of the types of analyses, and the definitions of each type of analysis. The reports involved studies of gabapentin used for medical reasons not approved for marketing by the US Food and Drug Administration, known as “off-label” uses. What Did the Researchers Do and Find? The researchers identified trials sponsored by Pfizer relating to four off-label uses of gabapentin and examined the internal company protocols, statistical analysis plans, research reports, and the main publications related to each trial. The researchers then compared the numbers of participants randomized and analyzed for the main (primary) outcome and the type of analysis for efficacy and safety in both the internal research report and the trial publication. The researchers identified 21 trials, 11 of which were published RCTs that had the associated documents necessary for comparison. The researchers found that in three out of ten trials there were differences in the internal research report and the main publication regarding the number of randomized participants. Furthermore, in six out of ten trials, the researchers were unable to compare the internal research report with the main publication for the number of participants analyzed for efficacy, because the research report either did not describe the primary outcome or did not describe the type of analysis. Overall, the researchers found that seven different types of efficacy analyses were described in the protocols, statistical analysis plans, and publications, including intention-to-treat analysis. However, the protocol or publication used six different descriptions for the intention-to-treat analysis, resulting in several important differences between the internal and published documents about the number of patients included in the analysis. What Do These Findings Mean? These findings from a sample of industry-sponsored trials on the off-label use of gabapentin suggest that when compared to the internal research reports, the trial publications did not always accurately reflect what was actually done in the trial. Therefore, the trial publication could not be considered to be an accurate and transparent record of the numbers of participants randomized and analyzed for efficacy. These findings support the need for further revisions of the CONSORT statement, such as including explicit statements about the criteria used to define each type of analysis and the numbers of participants excluded from each type of analysis. Further guidance is also needed to ensure consistent terminology for types of analysis. Of course, these revisions will improve reporting only if authors and journals adhere to them. These findings also highlight the need for all individual patient data to be made accessible to readers of the published article. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001378. For more information, see the CONSORT statement website The EQUATOR Network website is a resource center for the good reporting of health research studies and has more information about the SPIRIT initiative and the CONSORT statement