Lara A. Kahale

Legislative, educational, policy and other interventions targeting physicians’ interaction with pharmaceutical companies: a systematic review

Background Pharmaceutical company representatives likely influence the prescribing habits and professional behaviour of physicians. Objective The objective of this study was to systematically review the effects of interventions targeting practising physicians’ interactions with pharmaceutical companies. Eligibility criteria We included observational studies, non-randomised controlled trials (non-RCTs) and RCTs evaluating legislative, educational, policy or other interventions targeting the interactions between physicians and pharmaceutical companies. Data sources The search strategy included an electronic search of MEDLINE and EMBASE. Two reviewers performed duplicate and independent study selection, data abstraction and assessment of risk of bias. Appraisal and synthesis methods We assessed the risk of bias in each included study. We summarised the findings narratively because the nature of the data did not allow a meta-analysis to be conducted. We assessed the quality of evidence by outcome using the GRADE methodology. Results Of 11 189 identified citations, one RCT and three observational studies met the eligibility criteria. All four studies specifically targeted one type of interaction with pharmaceutical companies, that is, interactions with drug representatives. The RCT provided moderate quality evidence of no effect of a ‘collaborative approach’ between the pharmaceutical industry and a health authority. The three observational studies provided low quality evidence suggesting a positive effect of policies aiming to reduce interaction between physicians and pharmaceutical companies (by restricting free samples, promotional material, and meetings with pharmaceutical company representatives) on prescription behaviour. Limitations We identified too few studies to allow strong conclusions. Conclusions Available evidence suggests a potential impact of policies aiming to reduce interaction between physicians and drug representatives on physicians’ prescription behaviour. We found no evidence concerning interventions affecting other types of interaction with pharmaceutical companies.

Association between physicians’ interaction with pharmaceutical companies and their clinical practices: A systematic review and meta-analysis

Background Pharmaceutical company representatives likely influence the prescribing habits and professional behaviors of physicians. The objective of this study was to systematically review the association between physicians’ interactions with pharmaceutical companies and their clinical practices. Methods We used the standard systematic review methodology. Observational and experimental study designs examining any type of targeted interaction between practicing physicians and pharmaceutical companies were eligible. The search strategy included a search of MEDLINE and EMBASE databases up to July 2016. Two reviewers selected studies, abstracted data, and assessed risk of bias in duplicate and independently. We assessed the quality of evidence using the GRADE approach. Results Twenty articles reporting on 19 studies met our inclusion criteria. All of these studies were conducted in high-income countries and examined different types of interactions, including detailing, industry-funded continuing medical education, and receiving free gifts. While all included studies assessed prescribing behaviors, four studies also assessed financial outcomes, one assessed physicians’ knowledge, and one assessed their beliefs. None of the studies assessed clinical outcomes. Out of the 19 studies, 15 found a consistent association between interactions promoting a medication, and inappropriately increased prescribing rates, lower prescribing quality, and/or increased prescribing costs. The remaining four studies found both associations and lack of significant associations for the different types of exposures and drugs examined in the studies. A meta-analysis of six of these studies found a statistically significant association between exposure and physicians’ prescribing behaviors (OR = 2.52; 95% CI 1.82–3.50). The quality of evidence was downgraded to moderate for risk of bias and inconsistency. Sensitivity analysis excluding studies at high risk of bias did not substantially change these results. A subgroup analysis did not find a difference by type of exposure. Conclusion There is moderate quality evidence that physicians’ interactions with pharmaceutical companies are associated with their prescribing patterns and quality.

Handling trial participants with missing outcome data when conducting a meta-analysis: a systematic survey of proposed approaches

BackgroundWhen potentially associated with the likelihood of outcome, missing participant data represents a serious potential source of bias in randomized trials. Authors of systematic reviews frequently face this problem when conducting meta-analyses. The objective of this study is to conduct a systematic survey of the relevant literature to identify proposed approaches for how systematic review authors should handle missing participant data when conducting a meta-analysis.MethodsWe searched MEDLINE and the Cochrane Methodology register from inception to August 2014. We included papers that devoted at least two paragraphs to discuss a relevant approach for missing data. Five pairs of reviewers, working independently and in duplicate, selected relevant papers. One reviewer abstracted data from included papers and a second reviewer verified them. We summarized the results narratively.ResultsOf 9,138 identified citations, we included 11 eligible papers. Four proposed general approaches for handling dichotomous outcomes, and all recommended a complete case analysis as the primary analysis and additional sensitivity analyses using the following imputation methods: based on reasons for missingness (n = 3), relative to risk among followed up (n = 3), best-case scenario (n = 2), and worst-case scenario (n = 3). Three of these approaches suggested taking uncertainty into account. Two papers proposed general approaches for handling continuous outcomes, and both proposed a complete case analysis as the reference analysis and the following imputation methods as sensitivity analyses: based on reasons for missingness (n = 2), based on the mean observed in the same trial or other trials (n = 1), and based on informative missingness differences in means (n = 1). The remaining eligible papers did not propose general approaches but addressed specific statistical issues.ConclusionsAll proposed approaches for handling missing participant data recommend conducting a complete case analysis for the primary analysis and some form of sensitivity analysis to evaluate robustness of results. Although these approaches require further testing, they may guide review authors in addressing missing participant data.

Knowledge, beliefs and attitudes of physicians in low and middle-income countries regarding interacting with pharmaceutical companies: a systematic review

BackgroundUnderstanding the perceptions and attitudes of physicians is important. This knowledge assists in the efforts to reduce the impact of their interactions with the pharmaceutical industry on clinical practice. It appears that most studies on such perceptions and attitudes have been conducted in high-income countries. The objective was to systematically review the knowledge, beliefs and attitudes of physicians in low and middle-income countries regarding interactions with pharmaceutical companies.MethodsEligible studies addressed any type of interaction between physicians and pharmaceutical companies. The outcomes of interest included knowledge, beliefs and attitudes of practicing physicians. The search strategy covered MEDLINE and EMBASE databases. Two reviewers completed in duplicate and independently study selection, data abstraction, and assessment of methodological features. The data synthesis consisted of a narrative summary of the findings stratified by knowledge, beliefs and attitudes.ResultsWe included ten reports from nine eligible studies, each of which had a number of methodological limitations. Four studies found that the top perceived benefits of this interaction were receiving information and rewards. In five out of eight studies assessing the perception regarding the impact of the interaction on the behavior of physician prescription, the majority of participants believed it to be minor. In one of these studies, participants perceived that impact to be lesser when asked about their own behavior. The attitudes of physicians towards information and rewards provided by pharmaceutical company representatives (PCRs) (assessed in 5 and 2 studies respectively) varied across studies. In the only study assessing their attitudes towards pharmaceutical-sponsored Continuing Medical Education, physicians considered local conferences to have higher impact. Their attitudes towards developing policies restricting physicians’ interactions with PCRs were positive in two studies. In one study, the majority of participants did not mind the public knowing that physicians were receiving gifts and awards from drug companies.ConclusionsThis review identified few studies conducted in low and middle-income countries. While physicians generally perceived the impact of interactions on their behavior to be minor, their attitudes toward receiving information and rewards varied across studies.

Three challenges described for identifying participants with missing data in trials reports, and potential solutions suggested to systematic reviewers

OBJECTIVE To categorize the challenges in determining the extent of missing participant data in randomized trials and suggest potential solutions for systematic review authors. STUDY DESIGN AND SETTING During the process of updating a series of Cochrane systematic reviews on the topic of anticoagulation in patients with cancer, we identified challenges and used an iterative approach to improve, and a consensus process to agree on the challenges identified, and to suggest potential ways of dealing with them. The five systematic reviews included 58 trials and 75 meta-analyses for patient-important dichotomous outcomes with 27,037 randomized participants. RESULTS We identified three categories of challenges: (1) Although systematic reviewers require information about missing data to be reported by outcome, trialists typically report the information by participant; (2) It is not always clear whether the trialists followed up participants in certain categories (e.g., noncompliers), that is, whether some categories of participants did or did not have missing data; (3) It is not always clear how the trialists dealt with missing data in their analysis (e.g., exclusion from the denominator vs. assumptions made for the numerator). We discuss potential solutions for each one of these challenges and suggest further research work. CONCLUSION Current reporting of missing data is often not explicit and transparent, and although our potential solutions to problems of suboptimal reporting may be helpful, reliable and valid characterization of the extent and nature of missing data remains elusive. Reporting of missing data in trials needs further improvement.

Reporting missing participant data in randomised trials: systematic survey of the methodological literature and a proposed guide

Objectives We conducted a systematic survey of the methodological literature to identify recommended approaches for how and what randomised clinical trial (RCT) authors should report on missing participant data and, on the basis of these approaches, to propose guidance for RCT authors. Methods We defined missing participant data (MPD) as missing outcome data for trial participants. We considered both categorical and continuous outcome data. We searched MEDLINE and the Cochrane Methodology Register for articles in which authors proposed approaches to reporting MPD from RCTs. We selected eligible articles independently and in duplicate and extracted data in duplicate. Using an iterative process of discussion and revisions, we used the findings to develop guidance. Results Of 10 501 unique citations identified, 13 articles reporting on 10 approaches proved eligible. The identified approaches recommend reporting the following aspects (from most to least frequently recommended): number of participants with MPD (n=10), reasons for MPD (n=7), methods used to handle MPD in the analysis (n=4), flow of participants (n=3), pattern of missingness (eg, whether at random) (n=3), differences in rates of MPD between trial arms (n=2), differences between participants with and without MPD (n=2), results of any sensitivity analyses (n=2), implication of MPD on interpreting the results (n=2) and methods used to prevent missing data (n=1). We propose a guide with nine items related to reporting the number, reasons, patterns, analytical methods and interpretation of MPD. Conclusions Most identified approaches invite trial authors to report the extent of MPD and the underlying reasons. Fewer approaches focus on reporting missingness patterns, methods for handling MPD and implications of MPD on results. Our proposed guidance could help RCT authors to better report, and readers to better identify participants with missing data.

Impact of missing participant data for dichotomous outcomes on pooled effect estimates in systematic reviews: a protocol for a methodological study

BackgroundThere is no consensus on how authors conducting meta-analysis should deal with trial participants with missing outcome data. The objectives of this study are to assess in Cochrane and non-Cochrane systematic reviews: (1) which categories of trial participants the systematic review authors consider as having missing participant data (MPD), (2) how trialists reported on participants with missing outcome data in trials, (3) whether systematic reviewer authors actually dealt with MPD in their meta-analyses of dichotomous outcomes consistently with their reported methods, and (4) the impact of different methods of dealing with MPD on pooled effect estimates in meta-analyses of dichotomous outcomes.Methods/DesignWe will conduct a methodological study of Cochrane and non-Cochrane systematic reviews. Eligible systematic reviews will include a group-level meta-analysis of a patient-important dichotomous efficacy outcome, with a statistically significant effect estimate. Teams of two reviewers will determine eligibility and subsequently extract information from each eligible systematic review in duplicate and independently, using standardized, pre-piloted forms. The teams will then use a similar process to extract information from the trials included in the meta-analyses of interest. We will assess first which categories of trial participants the systematic reviewers consider as having MPD. Second, we will assess how trialists reported on participants with missing outcome data in trials. Third, we will compare what systematic reviewers report having done, and what they actually did, in dealing with MPD in their meta-analysis. Fourth, we will conduct imputation studies to assess the effects of different methods of dealing with MPD on the pooled effect estimates of meta-analyses. We will specifically calculate for each method (1) the percentage of systematic reviews that lose statistical significance and (2) the mean change of effect estimates across systematic reviews.DiscussionThe impact of different methods of dealing with MPD on pooled effect estimates will help judge the associated risk of bias in systematic reviews. Our findings will inform recommendations regarding what assumptions for MPD should be used to test the robustness of meta-analytical results.

Knowledge, Beliefs and Attitudes of Patients and the General Public towards the Interactions of Physicians with the Pharmaceutical and the Device Industry: A Systematic Review

Objective To systematically review the evidence on the knowledge, beliefs, and attitudes of patients and the general public towards the interactions of physicians with the pharmaceutical and the device industry. Methods We included quantitative and qualitative studies addressing any type of interactions between physicians and the industry. We searched MEDLINE and EMBASE in August 2015. Two reviewers independently completed data selection, data extraction and assessment of methodological features. We summarized the findings narratively stratified by type of interaction, outcome and country. Results Of the 11,902 identified citations, 20 studies met the eligibility criteria. Many studies failed to meet safeguards for protecting from bias. In studies focusing on physicians and the pharmaceutical industry, the percentages of participants reporting awareness was higher for office-use gifts relative to personal gifts. Also, participants were more accepting of educational and office-use gifts compared to personal gifts. The findings were heterogeneous for the perceived effects of physician-industry interactions on prescribing behavior, quality and cost of care. Generally, participants supported physicians’ disclosure of interactions through easy-to-read printed documents and verbally. In studies focusing on surgeons and device manufacturers, the majority of patients felt their care would improve or not be affected if surgeons interacted with the device industry. Also, they felt surgeons would make the best choices for their health, regardless of financial relationship with the industry. Participants generally supported regulation of surgeon-industry interactions, preferably through professional rather than governmental bodies. Conclusion The awareness of participants was low for physicians’ receipt of personal gifts. Participants also reported greater acceptability and fewer perceived influence for office-use gifts compared to personal gifts. Overall, there appears to be lower awareness, less concern and more acceptance of surgeon-device industry interactions relative to physician-pharmaceutical industry interactions. We discuss the implications of the findings at the patient, provider, organizational, and systems level.

A systematic survey of the methods literature on the reporting quality and optimal methods of handling participants with missing outcome data for continuous outcomes in randomized controlled trials

OBJECTIVE To conduct (1) a systematic survey of the reporting quality of simulation studies dealing with how to handle missing participant data (MPD) in randomized control trials and (2) summarize the findings of these studies. STUDY DESIGN AND SETTING We included simulation studies comparing statistical methods dealing with continuous MPD in randomized controlled trials addressing bias, precision, coverage, accuracy, power, type-I error, and overall ranking. For the reporting of simulation studies, we adapted previously developed criteria for reporting quality and applied them to eligible studies. RESULTS Of 16,446 identified citations, the 60 eligible generally had important limitations in reporting, particularly in reporting simulation procedures. Of the 60 studies, 47 addressed ignorable and 32 addressed nonignorable data. For ignorable missing data, mixed model was most frequently the best on overall ranking (9 times best, 34.6% of times tested) and bias (10, 55.6%). Multiple imputation was also performed well. For nonignorable data, mixed model was most frequently the best on overall ranking (7, 46.7%) and bias (8, 57.1%). Mixed model performance varied on other criteria. Last observation carried forward (LOCF) was very seldom the best performing, and for nonignorable MPD frequently the worst. CONCLUSION Simulation studies addressing methods to deal with MPD suffered from serious limitations. The mixed model approach was superior to other methods in terms of overall performance and bias. LOCF performed worst.Please cite this article as: Zhang Y, Alyass A, Vanniyasingam T, Sadeghirad B, Flórez ID, Pichika SC, Kennedy SA, Abdulkarimova U, Zhang Y, Iljon T, Morgano GP, Colunga Lozano LE, Aloweni FAB, Lopes LC, Yepes-Nuñez JJ, Fei Y, Wang L, Kahale LA, Meyre D, Akl EA, Thabane L, Guyatt G, Reporting quality and optimal methods of handling participants with missing outcome data for continuous outcomes in randomized controlled trials: a systematic survey of the methods literature, Journal of Clinical Epidemiology (2017), doi: 10.1016/j.jclinepi.2017.05.016.

Effectiveness of behavioral interventions to reduce the intake of sugar sweetened beverages among children and adolescents: A systematic review and meta-analysis

Abstract Context Consumption of sugar-sweetened beverages (SSBs) among children has been associated with adverse health outcomes. Numerous behavioral interventions aimed at reducing the intake of SSBs among children have been reported, yet evidence of their effectiveness is lacking. Objective This systematic review explored the effectiveness of educational and behavioral interventions to reduce SSB intake and to influence health outcomes among children aged 4 to 16 years. Data Sources Seven databases were searched for randomized controlled trials published prior to September 2016. Studies identified were screened for eligibility. Study Selection Trials were included in the review if they met the PICOS (Population, Intervention, Comparison, Outcome, and Study design) criteria for inclusion of studies. Data Extraction Data were extracted by 2 reviewers following Cochrane guidelines and using Review Manager software. Results Of the 16 trials included, 12 were school based and 4 were community or home based. Only 3 trials provided data that could be pooled into a meta-analysis for evaluating change in SSB intake. Subgroup analyses showed a trend toward a significant reduction in SSB intake in participants in school-based interventions compared with control groups. Change in body mass index z scores was not statistically significant between groups. Conclusions The quality of evidence from included trials was considered moderate, and the effectiveness of educational and behavioral interventions in reducing SSB intake was modest. Systematic Review Registration PROSPERO registration number CRD42014004432.