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Supplemental material, sj-pdf-1-jrs-10.1177_0141076821994535 for The US Food and Drug Administration’s authorisation of Purdue’s controlled-release methylphenidate for adult ADHD: comments on the regulatory practice by Kim Boesen, Karsten Juhl Jørgensen and Peter C Gøtzsche in Journal of the Royal Society of Medicine

Supplemental material, sj-pdf-1-jrs-10.1177_0141076821994535 for The US Food and Drug Administration’s authorisation of Purdue’s controlled-release methylphenidate for adult ADHD: comments on the regulatory practice by Kim Boesen, Karsten Juhl Jørgensen and Peter C Gøtzsche in Journal of the Royal Society of Medicine

Additional file 1.

An error occurred in the results sections of the abstract and main body of this research paper by Rasmussen et al (BMJ 2018;363:c3654, doi:10.1136/bmj.k3654). The number of studies reporting funder involvement in design should be 173 (87%) rather than 183 (92%).

Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.

The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in email discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, , introduction, methods, results, and discussion sections of articles. 18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the Web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies., Biyomedikal araştırmaların çoğu gözlemsel niteliktedir. Bu tür araştırma raporlarının yazımı sıklıkla yetersizdir. Bu durum gözlemsel araştırmaların güçlü ve zayıf yönlerinin ve genellenebilirliğinin değerlendirilmesini zorlaştırmaktadır. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) girişimi, tam ve doğru bir gözlemsel araştırma raporunun neleri içermesi gerektiği konusunda öneriler geliştirmiştir. Bu önerilerin kapsamı kohort, vaka-kontrol ve kesitsel çalışmalar olmak üzere üç ana çalışma tasarımını kapsayacak şekilde tanımlanmıştır. Eylül 2004’te, taslak kontrol listesinin maddelerini oluşturmak için araştırmacı, metodolog ve dergi editörlerinden oluşan iki günlük bir workshop yapılmıştır. Bu liste, deneysel kanıtları ve metodolojik varsayımları dikkate alan geniş bir STROBE katılımcı grubu ile birlikte e-mail tartışmasında ve koordinasyon grubunun yaptığı bir dizi toplantıda revize edilmiştir. Workshop ve arka arkaya tekrarlayan danışma ve revizyon süreci sonucunda makalenin başlık, özet, giriş, metot, bulgular ve tartışma bölümleri ile ilgili 22 maddeden oluşan bir kontrol listesi (STROBE Bildirimi) hazırlanmıştır. 18 madde her üç araştırma desenine de genel ve dört madde ise kohort, vaka-kontrol ve kesitsel çalışmalara özeldir. Ayrıca, buna ek olarak ayrıntılı bir Açıklama ve İşleme dokümanı yayınlanmıştır ve bu yayına PLoS Medicine, Annals of Internal Medicine ve Epidemiology’nin Web sitesinden ücretsiz olarak erişilebilir. STROBE Bildirimi’nin gözlemsel araştırma raporlarının yazım kalitesinin geliştirilmesine katkı sağlaması ümit edilmektedir.

Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate

Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. 18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the Web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies., This paper describes the recommendations of The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative on what should be included in an accurate and complete report of an observational study.

NSAIDs are widely used. Almost 10% of people in The Netherlands used a non-aspirin NSAID in 1987, and the overall use was 11 defined daily doses per 1000 population per day. In Australia in 1994, overall use was 35 defined daily doses per 1000 population a day, with 36% of the people receiving NSAIDs for osteoarthritis, 42% for sprain and strain or low back pain, and 4% for rheumatoid arthritis; 35% of the people receiving NSAIDs were aged over 60 years.We conducted a systematic review and aimed to answer the following clinical questions: Are there any important differences between NSAIDs? What are the effects of topical NSAIDs; and of co-treatments to reduce the risk of gastrointestinal adverse effects of NSAIDs? We searched: Medline, Embase, The Cochrane Library and other important databases up to December 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).We found 35 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.In this systematic review we present information relating to the benefits and harms of the following interventions: alternative analgesics, H(2) blockers, misoprostol, NSAIDs (systemic, topical, differences in efficacy between, dose-response relationship of), proton pump inhibitors.

There is a delicate balance between the benefits and harms of mammography screening, and women should decide for themselves, on an informed basis. The invitation to have a mammography is the only source of information provided to all eligible women, and we explored whether it provides such a basis. We collected invitations from English-speaking and Scandinavian countries. The major benefit of screening, a reduction in breast cancer mortality, was mentioned in 30 of 31 invitations, whereas the most important harms, overdiagnosis and overtreatment, were not mentioned in any of the invitations.

Objective: To investigate whether information on mammographic screening presented on websites by interest groups is balanced, is independent of source of funding, and reflects recent findings. Design: Cross sectional study using a checklist with 17 information items. Setting: 27 websites in Scandinavian and English speaking countries. Results: The 13 sites from advocacy groups and the 11 from governmental institutions all recommended mammographie screening, whereas the three from consumer organisations questioned screening (P = 0.0007). All the advocacy groups accepted industry funding, apparently without restrictions. In contrast the three consumer organisations acknowledged the risk of bias related to industry funding, and two of them did not accept such funding at all. Advocacy groups and governmental organisations favoured information items that shed positive light on screening. The major harms of screening, overdiagnosis and overtreatment, were mentioned by only four of these groups, but by all three sites from consumer organisations (P = 0.02). In addition, the chosen information was often misleading or erroneous. The selection of information items for websites did not reflect recent findings, apart from the consumer sites, which were much more balanced and comprehensive than other sites (median of 9 information items v 3 items, P = 0.03). Conclusions: The information material provided by professional advocacy groups and governmental organisations is information poor and severely biased in favour of screening. Few websites live up to accepted standards for informed consent such as those stated in the General Medical Council's guidelines.

OBJECTIVEFunding of systematic reviews by drug and device companies and other financial conflicts of interest among authors may have an impact on how the reviews areconducted. The aim of this study was to investigate if financial conflicts of interest are associated with results, conclusions, and methodological quality of systematic reviews.DESIGNThis is a Cochrane methodology review. We searched PubMed, EMBASE, and the Cochrane Methodology Register as well as the reference lists of included studies and Web of Science for studies citing the included studies. We included observational studies of any design that investigated samples of systematic reviews with and without industry funding or other financial conflicts of interest, published up to November 2016. For studies to be eligible, they had to investigate at least 1 of our outcomes: effect size estimates, statistically favorable results, favorable conclusions, and methodological quality. Two review authors independently extracted data and assessed risk of bias in relation to study inclusion, data extraction, and comparability of the investigated systematicreviews. We reported our findings on effect size estimates qualitatively. We calculated pooled risk ratios (RRs) with 95% confidence intervals for statistically favorable results, favorable conclusions, and methodological quality.RESULTSNine observational studies with a total of 983 systematic reviews of drug studies and 15 systematic reviews of device studies were included. Effect size estimates and frequency of statistically favorable results were similar between systematic reviews with and without financial conflicts of interest. Systematic reviews withfinancial conflicts of interest more often had favorable conclusions compared with systematic reviews without financial conflicts of interest (RR, 1.96; 95% CI, 1.23-3.13).CONCLUSIONSSystematic reviews with financial conflicts of interest related to drug and device companies more often have favorable conclusions and to some degree lowermethodological quality compared with systematic reviews without financial conflicts of interest. It remains unclear whether financial conflicts of interest have an impact on the results. OBJECTIVEFunding of systematic reviews by drug and device companies and other financial conflicts of interest among authors may have an impact on how the reviews are conducted. The aim of this study was to investigate if financial conflicts of interest are associated with results, conclusions, and methodological quality of systematic reviews.DESIGNThis is a Cochrane methodology review. We searched PubMed, EMBASE, and the Cochrane Methodology Register as well as the reference lists of included studies and Web of Science for studies citing the included studies. We included observational studies of any design that investigated samples of systematic reviews with and without industry funding or other financial conflicts of interest, published up to November 2016. For studies to be eligible, they had to investigate at least 1 of our outcomes: effect size estimates, statistically favorable results, favorable conclusions, and methodological quality. Two review authors independently extracted data and assessed risk of bias in relation to study inclusion, data extraction, and comparability of the investigated systematic reviews. We reported our findings on effect size estimates qualitatively. We calculated pooled risk ratios (RRs) with 95% confidence intervals for statistically favorable results, favorable conclusions, and methodological quality.RESULTSNine observational studies with a total of 983 systematic reviews of drug studies and 15 systematic reviews of device studies were included. Effect size estimates and frequency of statistically favorable results were similar between systematic reviews with and without financial conflicts of interest (Table). Systematic reviews with financial conflicts of interest more often had favorable conclusions compared with systematic reviews without financial conflicts of interest (RR, 1.96; 95% CI, 1.23-3.13). CONCLUSIONSSystematic reviews with financial conflicts of interest related to drug and device companies more often have favorable conclusions and to some degree lower methodological quality compared with systematic reviews without financial conflicts of interest. It remains unclear whether financial conflicts of interest have an impact on the results.

Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. It was first published in 1996 and updated in 2001. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have endorsed the CONSORT statement. The statement facilitates critical appraisal and interpretation of RCTs. During the 2001 CONSORT revision, it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports. A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement. After an expert meeting in January 2007, the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement. This update improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias. This explanatory and elaboration document-intended to enhance the use, understanding, and dissemination of the CONSORT statement-has also been extensively revised. It presents the meaning and rationale for each new and updated checklist item providing examples of good reporting and, where possible, references to relevant empirical studies. Several examples of flow diagrams are included. The CONSORT 2010 Statement, this revised explanatory and elaboration document, and the associated website (www.consort-statement.org) should be helpful resources to improve reporting of randomised trials.

Objectives To examine the extent of multiplicity of data in trial reports and to assess the impact of multiplicity on meta-analysis results. Design Empirical study on a cohort of Cochrane systematic reviews. Data sources All Cochrane systematic reviews published from issue 3 in 2006 to issue 2 in 2007 that presented a result as a standardised mean difference (SMD). We retrieved trial reports contributing to the first SMD result in each review, and downloaded review protocols. We used these SMDs to identify a specific outcome for each meta-analysis from its protocol. Review methods Reviews were eligible if SMD results were based on two to ten randomised trials and if protocols described the outcome. We excluded reviews if they only presented results of subgroup analyses. Based on review protocols and index outcomes, two observers independently extracted the data necessary to calculate SMDs from the original trial reports for any intervention group, time point, or outcome measure compatible with the protocol. From the extracted data, we used Monte Carlo simulations to calculate all possible SMDs for every meta-analysis. Results We identified 19 eligible meta-analyses (including 83 trials). Published review protocols often lacked information about which data to choose. Twenty-four (29%) trials reported data for multiple intervention groups, 30 (36%) reported data for multiple time points, and 29 (35%) reported the index outcome measured on multiple scales. In 18 meta-analyses, we found multiplicity of data in at least one trial report; the median difference between the smallest and largest SMD results within a meta-analysis was 0.40 standard deviation units (range 0.04 to 0.91). Conclusions Multiplicity of data can affect the findings of systematic reviews and meta-analyses. To reduce the risk of bias, reviews and meta-analyses should comply with prespecified protocols that clearly identify time points, intervention groups, and scales of interest.

Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. It was first published in 1996 and updated in 2001. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have endorsed the CONSORT statement. The statement facilitates critical appraisal and interpretation of RCTs. During the 2001 CONSORT revision, it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports. A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement. After an expert meeting in January 2007, the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement. This update improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias. This explanatory and elaboration document-intended to enhance the use, understanding, and dissemination of the CONSORT statement-has also been extensively revised. It presents the meaning and rationale for each new and updated checklist item providing examples of good reporting and, where possible, references to relevant empirical studies. Several examples of flow diagrams are included. The CONSORT 2010 Statement, this revised explanatory and elaboration document, and the associated website (www.consort-statement.org) should be helpful resources to improve reporting of randomised trials.