Does source of funding and conflict of interest influence the outcome and quality of spinal research?

Background/contextThere has been longstanding controversy surrounding the influence of funding source on the conduct and outcome of medical research. In 2011, a systematic review of the use of recombinant bone morphogenetic protein-2 revealed underreporting of unfavorable outcomes in some industry-sponsored trials. We hypothesize that Industrial funding and the presence of potential conflict of interest will be associated with low levels of evidence (LOE) and greater proportions of favorable outcomes in spinal research.PurposeThe aim of this study is to investigate the association between funding source and potential conflict of interest on the LOE and study outcome in the current spinal research.Study design/settingSystematic review of all the spinal publications in five leading spinal, orthopedics, neurosurgery, and general medical journals during 2010 (print and online). Supplements were included.Outcome measureOutcome and the LOE of research papers.MethodsTwo reviewers independently assessed all publications. Commentaries, editorials, letters, open operating theatres, case reports, narrative reviews, and study protocols were excluded. The self-reported potential conflict of interest and type of funding was extracted from each paper. Funding type was classified as foundation, industry, public, intramural, multiple (including industry), multiple (without industry), and unfunded. The outcome of each study was classified as favorable, unfavorable, equivocal, or not applicable. Clinical publications were ranked using the LOE guidelines produced by the Oxford Center for Evidence-Based Medicine.ResultsOverall, 1356 papers were analyzed, out of which 864 were suitable for LOE grading. There was good interobserver reliability for assignment of LOE grade, κ=0.897 (p<.01) and study outcome κ=0.804 (p<.01). A significant association was found between LOE and source of funding (p<.01). Industry-funded studies had the greatest proportion of level IV evidence (65%). There was a significant association between the funding source and study outcome (p=.01). The proportion of industry-funded studies with favorable outcomes (88%) was higher than that of publicly and foundation-funded studies (73% and 74%, respectively). The associated odds ratio for reporting favorable outcomes in industry-funded studies compared with studies with public and foundation funding was 2.7 (95% confidence interval [CI], 1.4–5.3), and 2.6 (95% CI, 1.3–5.2), respectively. A significant association between LOE and study outcome (p<.01) was also identified. Level I studies had the highest proportions of unfavorable (14%) and equivocal (23%) outcomes. Level IV studies had the highest proportion of favorable outcome (85%). There was no association between self-reported conflict of interest and LOE (p=.83) or study outcome (p=.25).ConclusionWe demonstrated a significant association between source of funding, study outcome, and LOE in spinal research. A large proportion of industry funded research was shown to provide level IV evidence and report favorable outcome.     

Civiale,stones and statistics: the dawn of evidence‐based medicine

The statistical research on bladder stones conducted by Paris urologist Jean Civiale in the early 19th century provided historical roots for evidence‐based medicine. Translations of original documents by Civiale describing his work on treating bladder stones, and the discussion by members of the Paris Academy of Sciences that commented on his results in 1835, were reviewed. By collecting statistical data on a wide scale throughout Europe, Civiale argued that his new transurethral procedure, called lithotripsy, was superior to the more widely used but highly morbid technique, lithotomy. The Paris Academy of Sciences commented on his research and chose the occasion to debate whether or not numerical reasoning and statistics had any place in medical and surgical practice. Civiale’s insights and methods espoused similar concepts and ideas driving today’s new paradigm of evidence‐based medicine.     

Randomised controlled trials as part of clinical care: A seven‐step routinisation framework proposal

Evidence translation in wound care relies on the need for evidence generation. Clinical practice may generate evidence only if evidence‐generating research projects, such as randomised controlled trials (RCTs), became routinised in clinical settings. The aim of this study was to identify optimal trial‐related practices to routinise trial‐related activities in Melbourne‐located wound clinics as reported by clinicians and researchers. We conducted a secondary analysis of the available data on how to routinise RCTs in clinical care, with a focus on enablers and suggestions provided by the participants during face‐to‐face and telephone interviews. Data were obtained from a qualitative observational study nested within a randomised, double‐blinded, placebo‐controlled trial on clinical effectiveness of aspirin as an adjunct to compression therapy in healing chronic venous leg ulcers (ASPiVLU). We developed a seven‐step Routinisation of Trials in Clinical Care Framework. These steps include: (1) pre‐trial clinical site assessment, (2) optimising pre‐recruitment arrangements, (3) developing and updating trial‐related skills, (4) embedding RCT recruitment as part of routine clinical care, (5) promoting teamwork and trial‐related collaboration, (6) addressing trial‐related financial issues, and (7) communicating trial results to clinicians.     

Systematic overview and critical appraisal of meta‐analyses of interventions in intensive care medicine

Rationale

Meta‐analysed intervention effect estimates are perceived to represent the highest level of evidence. However, such effects and the randomized clinical trials which are included in them need critical appraisal before the effects can be trusted.

Objective

Critical appraisal of a predefined set of all meta‐analyses on interventions in intensive care medicine to assess their quality and assessed the risks of bias in those meta‐analyses having the best quality.

Methods

We conducted a systematic search to select all meta‐analyses of randomized clinical trials on interventions used in intensive care medicine. Selected meta‐analyses were critically appraised for basic scientific criteria, (1) presence of an available protocol, (2) report of a full search strategy, and (3) use of any bias risk assessment of included trials. All meta‐analyses which qualified these criteria were scrutinized by full “Risk of Bias in Systematic Reviews” ROBIS evaluation of 4 domains of risks of bias, and a “Preferred Reporting Items for Systematic Reviews and Meta‐Analyses” PRISMA evaluation.

Results

We identified 467 meta‐analyses. A total of 56 meta‐analyses complied with these basic scientific criteria. We scrutinized the risks of bias in the 56 meta‐analyses by full ROBIS evaluation and a PRISMA evaluation. Only 4 meta‐analyses scored low risk of bias in all the 4 ROBIS domains and 41 meta‐analyses reported all 27 items of the PRISMA checklist.

Conclusion

In contrast with what might be perceived as the highest level of evidence only 0.9% of all meta‐analyses were judged to have overall low risk of bias.

     

Evidence‐based medicine training in residency: a survey of urology programme directors

OBJECTIVE

To investigate whether and in what format urology residents receive formal training in evidence‐based clinical practice.

METHODS

In 2007 we conducted a survey of the Accreditation Council for Graduate Medical Education (ACGME)‐accredited urology residency programmes in the USA. The survey instrument was sent to all programmes, using postal mailing, e‐mail and a web–based interface. Programme director and coordinator names and basic demographic information such as programme size and length were retrieved from the institutions’ websites and the ACGME database.

RESULTS

Of 117 ACGME‐accredited urology programmes, 108 responded (92.3%). Most respondents either agreed or strongly agreed with statements that formal evidence‐based medicine (EBM) training was valuable to urology residents (97, 89.8%) and should be part of all residency programme curricula (91, 84.3%). Eighty‐four programmes (77.8%) indicated that their curricula included formal educational activities related to EBM. These programmes provided a median (interquartile range) of 10 (4.8–25.0) h of EBM teaching per academic year. Most programmes (65.9%) provided fewer hours of EBM training than programme directors perceived as ideal. Asked what would make it easier to integrate EBM into the programme, respondents identified urology‐specific educational materials (33.3%), a formal curriculum (24.4%) and faculty development (16.3%) as central needs.

CONCLUSION

In this survey we found that most programme directors recognize formal EBM teaching as an important aspect of urology residency training. However, most programmes devote less time to EBM training than they would like, and urology‐specific resources have been lacking. These findings support increased efforts to provide urology residents with opportunities to learn EBM‐related knowledge and skills in a variety of educational formats.     

Evaluating the evidence: the methodological and reporting quality of comparative observational studies of surgical interventions in urological publications

OBJECTIVE

To develop and apply a standardized evaluation form for assessing the methodological and reporting quality of observational studies of surgical interventions in urology.

METHODS

An evaluation standard was developed using the Consolidated Standards for Reporting Trials statement and previously reported surgical reporting quality instruments. Consensus scoring among three reviewers was developed using two distinct sets of studies. All comparative observational trials involving therapeutic surgical procedures published in four major urological journals in 1995 and 2005 were randomly assigned to each reviewer. Categories of reporting adequacy included background, intervention, statistical analysis, results and discussion.

RESULTS

Twenty‐seven articles in 1995 and 62 in 2005 met the inclusion criteria; 90% of studies were retrospective. From 1995 to 2005, the overall reporting quality score increased by 3.9 points (95% confidence interval, CI, 2.7–5.9; P = 0.001), from a mean (sd ) of 19.1 (3.9) to 23.0 (4.2) on a scale of 0–42. There were significant improvements in the reporting categories of study background (+0.7 points, 95% CI 0.1–1.3, P = 0.043, 0–8‐point scale), intervention (+1.6 points, 0.8–2.3, P = 0.001, 0–9‐point scale), and statistical analysis (+0.8 points, 0.2–1.4, P = 0.006, 0–9‐point scale). There were smaller and statistically insignificant improvements for results (+0.5 points, ?0.3 to 1.2, P = 0.217, 0–10‐point scale) and discussion reporting (+0.4 points, ?0.1 to 0.8, P = 0.106, 0–6‐point scale).

CONCLUSIONS

There have been minor improvements in the reporting of observational studies of surgical intervention between 1995 and 2005. However, reporting quality remains suboptimal. Clinical investigators, reviewers and journal editors should continue to strive for transparent reporting of the observational studies representing the bulk of the clinical evidence for urological procedures.     

Staying at the cutting edge: a review and analysis of evidence reporting and grading; the recommendations of the American Urological Association

The American Urological Association (AUA), as the premier urological organization in the USA, has been a pioneering force in the development of practice guidelines. Recently the AUA evaluated their guidelines development procedures and implemented several changes that resulted in more scientifically rigorous, transparent and efficient processes. These changes include narrowing the scope of the guideline, strengthening the systematic literature review, updating data‐analysis capabilities, altering panel members’ roles to exclude laborious data extraction, and identifying and specifying levels of evidence for guideline recommendations. In addition to a more scientifically sound guideline, the outcome of these modifications is a timely, less costly document involving fewer burdens on panel members.     

Analysis of run-in and treatment data in a wound outcomes registry: clinical impact of topical platelet-rich plasma gel on healing trajectory

Randomised controlled trials in chronic wounds typically exclude patients with comorbidities and confounding factors. Well‐designed observational studies can provide complementary clinical evidence that randomised trials cannot address. This study determined if wound care registry outcomes could be an alternative data source and if the results would be robust and valid. Changes in wound area and depth were hypothesised to be different between run‐in therapies and platelet‐rich plasma (AutoloGel?, Cytomedix, Inc) treatment. From a treatment registry of 285 chronic wounds, 46 had run‐in and post‐treatment data. Seven chronic wound categories were identified. Mean wound age at study start was 52·4 days. General linear model repeated measures showed a credible and robust data set. Statistically significant differences for wound area and depth were observed between run‐in and post‐treatment period at multiple time points. Wound area and depth ≥50% reduction were analysed using Kaplan–Meier methods. During run‐in, 15% of wound area improved compared to 28% post‐treatment and 11% of wound depth improved during run‐in compared to 39% post‐treatment. Significant clinical outcomes indicated many previously non responsive wounds began actively healing in response to platelet‐rich plasma therapy, indicating that registry data can be used as a complementary source of evidence.     

Influence of diabetes mellitus on postoperative complications and failure in head and neck free flap reconstruction: A systematic review and meta‐analysis

We performed a systematic review and meta‐analysis to determine whether diabetic patients have an increased rate of postoperative complications compared to nondiabetic patients after head and neck free flap reconstruction. A systematic review of PubMed Database between 1966 and 2012 was performed. RevMan 5.0 was used for meta‐analysis. A retrospective medical chart review of 7890 patients to identify those who had a failed microsurgical reconstruction of the head and neck region at Chang Gung Memorial Hospital was also carried out. The result revealed that patients with diabetes mellitus have a 1.76 increased risk of complications (odds ratio [OR] = 1.76; 95% confidence interval [CI] = 1.11–2.79) with minimal heterogeneity (I ² = 22%; p = .28). The prevalence of diabetes mellitus in patients with failed free flaps for head and neck reconstruction is 15%. The incidence of diabetes mellitus in these patients with failed free flaps is 2.3 times higher than in the general population.<copy;2013> © 2014 Wiley Periodicals, Inc. Head Neck 37 : 615–618, 2015     

A cross‐sectional study to quantify the prevalence of avian influenza viruses in poultry at intervention and non‐intervention live bird markets in central Vietnam, 2014

In Vietnam, live bird markets are found in most populated centres, providing the means by which fresh poultry can be purchased by consumers for immediate consumption. Live bird markets are aggregation points for large numbers of poultry, and therefore, it is common for a range of avian influenza viruses to be mixed within live bird markets as a result of different poultry types and species being brought together from different geographical locations. We conducted a cross‐sectional study in seven live bird markets in four districts of Thua Thien Hue Province in August and December, 2014. The aims of this study were to (i) document the prevalence of avian influenza in live bird markets (as measured by virus isolation); and (ii) quantify individual bird‐, seller‐ and market‐level characteristics that rendered poultry more likely to be positive for avian influenza virus at the time of sale. A questionnaire soliciting details of knowledge, attitude and avian influenza practices was administered to poultry sellers in study markets. At the same time, swabs and faecal samples were collected from individual poultry and submitted for isolation of avian influenza virus. The final data set comprised samples from 1,629 birds from 83 sellers in the seven live bird markets. A total of 113 birds were positive for virus isolation; a prevalence of 6.9 (95% CI 5.8–8.3) avian influenza virus‐positive birds per 100 birds submitted for sale. After adjusting for clustering at the market and individual seller levels, none of the explanatory variables solicited in the questionnaire were significantly associated with avian influenza virus isolation positivity. The proportions of variance at the individual market, seller and individual bird levels were 6%, 48% and 46%, respectively. We conclude that the emphasis of avian influenza control efforts in Vietnam should be at the individual seller level as opposed to the market level.     

Role of ultrasound compared to age‐related formulas for uncuffed endotracheal intubation in a pediatric population

Background: It is often difficult to determine the correct size of endotracheal tubes (ETT) needed for intubating pediatric patients. Therefore, we evaluated the role of ultrasound in pediatric patients to compare the correct size of an uncuffed (ETT) with the minimal transverse diameter of the subglottic airway (MTDSA) measured by ultrasound and with tube size predicted by different age‐related formulas. Methods: A total of 50 pediatric patients ≤5 years were enrolled. As a standard, we defined the adequate ETT size with no audible leakage below a ventilation pressure of 15 mbar and with an audible leakage above 25 mbar. The maximum allowed difference between the prediction method result and the ETT that fit was defined as 0.3 mm. Ultrasound was performed before the intubation procedure; the intubating anesthesiologists were blinded to the results of the ultrasound measurement. Agreement between the two age‐based formulas most commonly used at our department and MTDSA with the correct ETT size (standard) was analyzed using a Bland–Altman plot. Correlation and regression analyses were performed and the numbers of correct intubation trials recorded. Results: The frequency of bias ≤0.3 mm between each method and the correct ETT in the first attempt was <50% and the mean number of reintubations 1.6 ± 1.3. In contrast to age‐related formulas, however, the ultrasonographically determined MTDSA was not significantly different from the correct ETT. MTDSA was highly associated with the outer diameter of the ETT (r = 0.869, R² = 0.754). Conclusions: Measuring MTDSA by ultrasound facilitates selection of the appropriate ETT in pediatric patients and may reduce the number of reintubations.     

Assessment of Farmer Knowledge of Large Ruminant Health and Production in Developing Village‐Level Biosecurity in Northern Lao PDR

The purpose of this study was to determine baseline knowledge and identify knowledge gaps of farmers on biosecurity, risk of transmission of transboundary diseases and large ruminant health and production in three provinces of northern Laos, Hua Phan (HP), Luang Prabang (LPB) and Xieng Khoung (XK). The survey was conducted in six villages that are project sites for an Australian Centre for International Agricultural Research (ACIAR) project, with two villages located in each of the three provinces. A census survey was conducted by interview with all 238 farmers participating in the ACIAR project, using a structured questionnaire. The interviews were conducted in Lao language and took 1–2 h per farmer. The answers were recorded in Lao and the survey data were translated into English and transcribed into Microsoft Excel, and a linear mixed model in the Genstat statistical analysis package was used to compare quantitative traits between the target provinces. The results showed that the prediction mean of farmer knowledge scores on parasitic disorders, infectious disease, reproduction and nutrition management were significantly different between the target provinces. The prediction mean of farmer knowledge scores on infectious disease questions ranged between 5.11 in HP to 8.54 in XK of 24 marks (P < 0.001). The prediction mean of total knowledge scores was 13.48 in LPB and 19.29 in XK of 42 marks (P < 0.001). The results indicate both the need for and scope required to attain improvements in farmer knowledge of large ruminant health and production. It was concluded that a participatory research and extension programme to address village‐level biosecurity and reduce disease risks, plus enhance large ruminant production capabilities of smallholder producers, is a valid and potentially important strategy to address transboundary disease risk and rural poverty in northern Laos.