ACcurate COnsensus Reporting Document (ACCORD) explanation and elaboration: Guidance and examples to support reporting consensus methods.

BACKGROUND: When research evidence is limited, inconsistent, or absent, healthcare decisions and policies need to be based on consensus amongst interested stakeholders. In these processes, the knowledge, experience, and expertise of health professionals, researchers, policymakers, and the public are systematically collected and synthesised to reach agreed clinical recommendations and/or priorities. However, despite the influence of consensus exercises, the methods used to achieve agreement are often poorly reported. The ACCORD (ACcurate COnsensus Reporting Document) guideline was developed to help report any consensus methods used in biomedical research, regardless of the health field, techniques used, or application. This explanatory document facilitates the use of the ACCORD checklist. METHODS AND FINDINGS: This paper was built collaboratively based on classic and contemporary literature on consensus methods and publications reporting their use. For each ACCORD checklist item, this explanation and elaboration document unpacks the pieces of information that should be reported and provides a rationale on why it is essential to describe them in detail. Furthermore, this document offers a glossary of terms used in consensus exercises to clarify the meaning of common terms used across consensus methods, to promote uniformity, and to support understanding for consumers who read consensus statements, position statements, or clinical practice guidelines. The items are followed by examples of reporting items from the ACCORD guideline, in text, tables and figures. CONCLUSIONS: The ACCORD materials - including the reporting guideline and this explanation and elaboration document - can be used by anyone reporting a consensus exercise used in the context of health research. As a reporting guideline, ACCORD helps researchers to be transparent about the materials, resources (both human and financial), and procedures used in their investigations so readers can judge the trustworthiness and applicability of their results/recommendations.

ACCORD (ACcurate COnsensus Reporting Document): A reporting guideline for consensus methods in biomedicine developed via a modified Delphi.

BACKGROUND: In biomedical research, it is often desirable to seek consensus among individuals who have differing perspectives and experience. This is important when evidence is emerging, inconsistent, limited, or absent. Even when research evidence is abundant, clinical recommendations, policy decisions, and priority-setting may still require agreement from multiple, sometimes ideologically opposed parties. Despite their prominence and influence on key decisions, consensus methods are often poorly reported. Our aim was to develop the first reporting guideline dedicated to and applicable to all consensus methods used in biomedical research regardless of the objective of the consensus process, called ACCORD (ACcurate COnsensus Reporting Document). METHODS AND FINDINGS: We followed methodology recommended by the EQUATOR Network for the development of reporting guidelines: a systematic review was followed by a Delphi process and meetings to finalize the ACCORD checklist. The preliminary checklist was drawn from the systematic review of existing literature on the quality of reporting of consensus methods and suggestions from the Steering Committee. A Delphi panel (n = 72) was recruited with representation from 6 continents and a broad range of experience, including clinical, research, policy, and patient perspectives. The 3 rounds of the Delphi process were completed by 58, 54, and 51 panelists. The preliminary checklist of 56 items was refined to a final checklist of 35 items relating to the article title (n = 1), introduction (n = 3), methods (n = 21), results (n = 5), discussion (n = 2), and other information (n = 3). CONCLUSIONS: The ACCORD checklist is the first reporting guideline applicable to all consensus-based studies. It will support authors in writing accurate, detailed manuscripts, thereby improving the completeness and transparency of reporting and providing readers with clarity regarding the methods used to reach agreement. Furthermore, the checklist will make the rigor of the consensus methods used to guide the recommendations clear for readers. Reporting consensus studies with greater clarity and transparency may enhance trust in the recommendations made by consensus panels.

Existing guidance on reporting of consensus methodology: a systematic review to inform ACCORD guideline development.

OBJECTIVE: To identify evidence on the reporting quality of consensus methodology and to select potential checklist items for the ACcurate COnsensus Reporting Document (ACCORD) project to develop a consensus reporting guideline. DESIGN: Systematic review. DATA SOURCES: Embase, MEDLINE, Web of Science, PubMed, Cochrane Library, Emcare, Academic Search Premier and PsycINFO from inception until 7 January 2022. ELIGIBILITY CRITERIA: Studies, reviews and published guidance addressing the reporting quality of consensus methodology for improvement of health outcomes in biomedicine or clinical practice. Reports of studies using or describing consensus methods but not commenting on their reporting quality were excluded. No language restrictions were applied. DATA EXTRACTION AND SYNTHESIS: Screening and data extraction of eligible studies were carried out independently by two authors. Reporting quality items addressed by the studies were synthesised narratively. RESULTS: Eighteen studies were included: five systematic reviews, four narrative reviews, three research papers, three conference abstracts, two research guidance papers and one protocol. The majority of studies indicated that the quality of reporting of consensus methodology could be improved. Commonly addressed items were: consensus panel composition; definition of consensus and the threshold for achieving consensus. Items least addressed were: public patient involvement (PPI); the role of the steering committee, chair, cochair; conflict of interest of panellists and funding. Data extracted from included studies revealed additional items that were not captured in the data extraction form such as justification of deviation from the protocol or incentives to encourage panellist response. CONCLUSION: The results of this systematic review confirmed the need for a reporting checklist for consensus methodology and provided a range of potential checklist items to report. The next step in the ACCORD project builds on this systematic review and focuses on reaching consensus on these items to develop the reporting guideline. PROTOCOL REGISTRATION: https://osf.io/2rzm9.

ACCORD guideline for reporting consensus-based methods in biomedical research and clinical practice: a study protocol.

BACKGROUND: Structured, systematic methods to formulate consensus recommendations, such as the Delphi process or nominal group technique, among others, provide the opportunity to harness the knowledge of experts to support clinical decision making in areas of uncertainty. They are widely used in biomedical research, in particular where disease characteristics or resource limitations mean that high-quality evidence generation is difficult. However, poor reporting of methods used to reach a consensus - for example, not clearly explaining the definition of consensus, or not stating how consensus group panellists were selected - can potentially undermine confidence in this type of research and hinder reproducibility. Our objective is therefore to systematically develop a reporting guideline to help the biomedical research and clinical practice community describe the methods or techniques used to reach consensus in a complete, transparent, and consistent manner. METHODS: The ACCORD (ACcurate COnsensus Reporting Document) project will take place in five stages and follow the EQUATOR Network guidance for the development of reporting guidelines. In Stage 1, a multidisciplinary Steering Committee has been established to lead and coordinate the guideline development process. In Stage 2, a systematic literature review will identify evidence on the quality of the reporting of consensus methodology, to obtain potential items for a reporting checklist. In Stage 3, Delphi methodology will be used to reach consensus regarding the checklist items, first among the Steering Committee, and then among a broader Delphi panel comprising participants with a range of expertise, including patient representatives. In Stage 4, the reporting guideline will be finalised in a consensus meeting, along with the production of an Explanation and Elaboration (E&E) document. In Stage 5, we plan to publish the reporting guideline and E&E document in open-access journals, supported by presentations at appropriate events. Dissemination of the reporting guideline, including a website linked to social media channels, is crucial for the document to be implemented in practice. DISCUSSION: The ACCORD reporting guideline will provide a set of minimum items that should be reported about methods used to achieve consensus, including approaches ranging from simple unstructured opinion gatherings to highly structured processes.

The Carbon Costs of In-Person Versus Virtual Medical Conferences for the Pharmaceutical Industry: Lessons from the Coronavirus Pandemic.

BACKGROUND: Many in-person congresses have shifted to a virtual format owing to coronavirus disease 2019 (COVID-19). We assessed carbon emissions savings associated with virtual attendance at international medical congresses for a mid-sized pharmaceutical company, to identify which aspects are driving the carbon cost. METHODS: We assessed carbon emissions that were the responsibility of company attendees (including their guests) for the most attended congresses by employees (American Society of Clinical Oncology [ASCO], European Neuroendocrine Tumor Society [ENETS], European Society for Medical Oncology [ESMO], World Congress for NeuroRehabilitation [WCNR]). For in-person estimates, we considered travel, accommodation and congress attendance; for online estimates, we considered office and internet-related energy use. Emissions were defined using recognised data sources. RESULTS: For 1723 anticipated in-person attendees, calculated total carbon emissions were 3,262,574 kgCO2e (mean per in-person company attendee, 1894 kgCO2e: ASCO, 4172; ESMO, 1479; WCNR, 1153; ENETS, 1009). For context, the average UK resident's annual carbon footprint is 5600 kgCO2e. Travel accounted for 91-96% of total emissions, mainly through long distance and business-class air travel. Calculated total carbon emissions associated with 1839 virtual attendees were 19,095 kgCO2e (mean per virtual company attendee, 10.4 kgCO2e; equivalent to approximately 0.3-1.1% of in-person attendance emissions across all four congresses assessed). CONCLUSION: Carbon emissions associated with virtual attendance were two orders of magnitude lower than for in-person attendance, and therefore the benefits of in-person attendance at medical congresses must be balanced against the carbon cost. Due diligence around who should attend and how they should travel to face-to-face meetings, and consideration of hybrid and domestic satellite options could be part of a balanced solution to reducing carbon emissions.

Open Pharma recommendations for plain language summaries of peer-reviewed medical journal publications.

Plain language summaries of peer-reviewed medical journal publications are a means of sharing research with a broad range of audiences and may improve the transparency, accountability, accessibility, discoverability, and inclusivity of medical research. There is currently an ongoing, industry-wide effort to establish consensus on plain language summaries, and initiatives are already in place that provide detailed guidance on plain language best practice, co-creation methods, patient-focused content, graphic and digital considerations, and publisher-specific guidelines. However, there remains a need for a foundational set of recommendations that complement existing initiatives to outline the minimum steps needed to develop discoverable, plain language summaries that are trustworthy, credible, and of high quality. Here, we present the Open Pharma recommendations for plain language summaries of peer-reviewed medical journal publications. These recommendations were initially developed by the Open Pharma Accessibility workstream and were extensively reviewed and refined during an expert roundtable and a focused, public consultation. Open Pharma is a multi-sponsor collaboration of pharmaceutical companies, non-pharmaceutical funders, publishers, patients, academics, regulators, editors, and societies seeking to identify and drive positive changes in the publishing of pharmaceutical company-funded research. We recommend that plain language summaries should be in the style of an abstract, free of technical jargon, unbiased, non-promotional, peer reviewed, and easily accessed. Plain language summaries should also meet the technical requirements to be indexed in directories such as PubMed. Ultimately, these recommendations are intended to be a concise outline of a minimum standard that provides top-line guidance on plain language summaries for authors, medical writers, publishers, and research funders.

PLAIN LANGUAGE SUMMARYArticles published in peer-reviewed medical journals are written using technical language. Plain language summaries are short summaries of these articles, written in everyday language that is easy to understand by anyone interested in medical research. This can include patients, patient advocates, caregivers, healthcare professionals, and policymakers. Sharing research through plain language summaries makes medical information more accessible and inclusive. However, few medical research articles include plain language summaries. The pharmaceutical industry has an opportunity to improve everyone's understanding of medical research by regularly developing plain language summaries of their articles. Plain language summaries can come in many different formats such as infographics and videos. However, text-only summaries are the easiest to find on internet search engines and research websites such as PubMed. Currently, there is limited guidance available to help researchers and medical journal publishers develop plain language summaries for their articles. In this article, 'Open Pharma recommendations for plain language summaries of peer-reviewed medical journal publications', we suggest a set of simple rules to help authors make and share text-only plain language summaries that we believe are possible for all articles reporting medical research. Once these have been met, we encourage researchers to consider making and sharing infographics and video summaries as well, to help people to understand their research even more.

Surgical Outcomes in Patients With Endometriosis: A Systematic Review.

OBJECTIVE: Among women treated surgically for endometriosis-associated pain, comprehensive data are lacking on the proportions of patients who experience little or no symptom relief, develop recurrent symptoms, or require further surgical treatment for endometriosis. The aim of this study was to assess the efficacy of surgical procedures used to treat endometriosis-associated pain. METHODS: Medline and Embase were searched on October 13, 2016. Articles referring to women undergoing surgery for the treatment of endometriosis-associated pain were screened by two independent investigators. For each included treatment arm, data were extracted for the proportion of patients reporting partial or no improvement after surgery for endometriosis-associated pain, pain recurrence, or requirement for further surgery. RESULTS: A total of 38 studies were included. Most studies did not report relevant outcomes to evaluate pain (71.1%) and recurrent surgery (68.4%). Of the women who underwent lesion excision, 11.8% reported no improvement in pain, and 22.6% underwent further surgery. Postoperative pain, recurrent pain, and adverse events were reported by 34.3%, 28.7%, and 14.8%, respectively, of patients who underwent excision or ablation of endometriosis combined with pelvic denervation and in 25.0%, 15.8%, and 8.1% of women who underwent lesion excision alone. Of the patients who were treated surgically for deep endometriosis affecting the bowel and/or bladder, 7.0% experienced recurrent symptoms, and 4.1% underwent further surgery. CONCLUSION: This review supports the findings of previous studies and highlights the need for standardized reporting and more detailed follow-up after surgery for endometriosis-associated pain.

Professional medical writing support and the quality, ethics and timeliness of clinical trial reporting: a systematic review.

BACKGROUND: Many authors choose to work with professional medical writers when reporting the results of clinical trials. We conducted a systematic review to examine the relationship between professional medical writing support (PMWS) and the quality, ethics and timeliness of publications reporting clinical trials. METHODS: Using terms related to 'medical writer' and 'observational study', we searched MEDLINE and Embase (no date limits), as well as abstracts and posters from meetings of the International Society for Medical Publication Professionals (ISMPP; 2014-2018). We also hand-searched the journals Medical Writing and The Write Stuff (2014-2018) and the bibliographies of studies identified in the electronic searches. We screened the results to identify studies that compared the quality, ethics and timeliness of clinical trial publications written with and without declared PMWS. RESULTS: Our searches identified 97 potentially relevant studies, of which 89 were excluded during screening and full paper review. The remaining eight studies compared 849 publications with PMWS with 2073 articles developed without such support. In these eight studies, PMWS was shown to be associated with increased adherence to Consolidated Standards of Reporting Trials (CONSORT) guidelines (in 3/3 studies in which this was assessed), publication in journals with an impact factor (one study), a higher quality of written English (one study), and a lower likelihood of reporting non-pre-specified outcomes (one study). PMWS was not associated with increased adherence to CONSORT for Abstracts guidelines (one study) or with the impact of published articles (mean number of citations per year, mean number of article views per year and Altmetric score; one study). In studies that assessed timeliness of publication, PMWS was associated with a reduced time from last patient visit in clinical trials to primary publication (one study), whereas time from submission to acceptance showed inconsistent results (two studies). CONCLUSIONS: This systematic review of eight observational studies suggests that PMWS is positively associated with measures of overall quality of reporting of clinical trials and may improve the timeliness of publication.

Professional medical writing support and the reporting quality of randomized controlled trial abstracts among high-impact general medical journals.

Background: In articles reporting randomized controlled trials, professional medical writing support is associated with increased adherence to Consolidated Standards of Reporting Trials (CONSORT). We set out to determine whether professional medical writing support was also associated with improved adherence to CONSORT for Abstracts. Methods: Using data from a previously published cross-sectional study of 463 articles reporting randomized controlled trials published between 2011 and 2014 in five top medical journals, we determined the association between professional medical writing support and CONSORT for Abstracts items using a Wilcoxon rank-sum test. Results: The mean proportion of adherence to CONSORT for Abstracts items reported was similar with and without professional medical writing support (64.3% vs 66.5%, respectively; p=0.30). Professional medical writing support was associated with lower adherence to reporting study setting (relative risk [RR]; 0.40; 95% confidence interval [CI], 0.23-0.70), and higher adherence to disclosing harms/side effects (RR 2.04; 95% CI, 1.37-3.03) and funding source (RR 1.75; 95% CI, 1.18-2.60). Conclusions: Although professional medical writing support was not associated with increased overall adherence to CONSORT for Abstracts, important aspects were improved with professional medical writing support, including reporting of adverse events and funding source. This study identifies areas to consider for improvement.

Reevaluating response and failure of medical treatment of endometriosis: a systematic review.

OBJECTIVE: To assess patient response rates to medical therapies used to treat endometriosis-associated pain. DESIGN: A systematic review with the use of Medline and Embase. SETTING: Not applicable. PATIENT(S): Women receiving medical therapy to treat endometriosis. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): The proportions of patients who: experienced no reduction in endometriosis-associated pain symptoms; had pain symptoms remaining at the end of the treatment period; had pain recurrence after treatment cessation; experienced an increase or no change in disease score during the study; were satisfied with treatment; and discontinued therapy owing to adverse events or lack of efficacy. The change in pain symptom severity experienced during and after treatment, as measured on the visual analog scale, was also assessed. RESULT(S): In total, 58 articles describing 125 treatment arms met the inclusion criteria. Data for the response of endometriosis-associated pain symptoms to treatment were presented in only 29 articles. The median proportions of women with no reduction in pain were 11%-19%; at the end of treatment, 5%-59% had pain remaining; and after follow-up, 17%-34% had experienced recurrence of pain symptoms after treatment cessation. After median study durations of 2-24 months, the median discontinuation rates due to adverse events or lack of efficacy were 5%-16%. CONCLUSION(S): Few studies of medical therapies for endometriosis report outcomes that are relevant to patients, and many women gain only limited or intermittent benefit from treatment.

Professional medical writing support and the quality of randomised controlled trial reporting: a cross-sectional study.

OBJECTIVES: Authors may choose to work with professional medical writers when writing up their research for publication. We examined the relationship between medical writing support and the quality and timeliness of reporting of the results of randomised controlled trials (RCTs). DESIGN: Cross-sectional study. STUDY SAMPLE: Primary reports of RCTs published in BioMed Central journals from 2000 to 16 July 2014, subdivided into those with medical writing support (n=110) and those without medical writing support (n=123). MAIN OUTCOME MEASURES: Proportion of items that were completely reported from a predefined subset of the Consolidated Standards of Reporting Trials (CONSORT) checklist (12 items known to be commonly poorly reported), overall acceptance time (from manuscript submission to editorial acceptance) and quality of written English as assessed by peer reviewers. The effect of funding source and publication year was examined. RESULTS: The number of articles that completely reported at least 50% of the CONSORT items assessed was higher for those with declared medical writing support (39.1% (43/110 articles); 95% CI 29.9% to 48.9%) than for those without (21.1% (26/123 articles); 95% CI 14.3% to 29.4%). Articles with declared medical writing support were more likely than articles without such support to have acceptable written English (81.1% (43/53 articles); 95% CI 67.6% to 90.1% vs 47.9% (23/48 articles); 95% CI 33.5% to 62.7%). The median time of overall acceptance was longer for articles with declared medical writing support than for those without (167 days (IQR 114.5-231 days) vs 136 days (IQR 77-193 days)). CONCLUSIONS: In this sample of open-access journals, declared professional medical writing support was associated with more complete reporting of clinical trial results and higher quality of written English. Medical writing support may play an important role in raising the quality of clinical trial reporting.

Iloprost for children with pulmonary hypertension after surgery to correct congenital heart disease.

Congenital heart disease (CHD) can cause pulmonary hypertension (PH) in children, and surgery to correct CHD may be complicated by postoperative pulmonary hypertensive crises (PHC). Clinical data regarding the use of inhaled iloprost to treat children with PH are scarce. Our aim was to determine the efficacy and safety of iloprost in children with PH following surgery to correct CHD. This was a randomized, placebo-controlled study of 22 children (median age 7 months) undergoing surgery to achieve biventricular repair. The combined clinical endpoint was a decrease of more than 20% in the ratio of systolic pulmonary arterial pressure to systolic arterial pressure or pulmonary resistance to systemic resistance, with no PHC or death. Patients were randomized to receive low-dose iloprost (30 ng/kg/min), high-dose iloprost (50 ng/kg/min), or placebo, for 10 min every 2 hr in the first 48 hr after surgery. PHC were experienced by two patients who received placebo and one patient treated with high-dose iloprost. The combined clinical endpoint was reached by six patients administered low-dose iloprost (P = 0.005) and four administered high-dose iloprost (P = 0.077), compared with none in the placebo group. Patients treated with iloprost showed a significant reduction from baseline in mean pulmonary vascular resistance index (-2.2 Wood units, P < 0.05), whereas patients who received placebo showed no significant change. This study supports the use of iloprost to treat children with PH following surgery to correct CHD.

An example of designed multiple ligands spanning protein classes: dual MCH-1R antagonists/DPPIV inhibitors.

A ligand-based approach to identify potential starting points for a dual MCH-1R antagonist/DPPIV inhibitor medicinal chemistry program was undertaken. Potential ligand pairs were identified by analysis of MCH-1R and DPPIV in vitro data. A highly targeted synthetic effort lead to the discovery of pyridone 11, a dual MCH-1R antagonist/DPPIV inhibitor with selectivity over DPP8 and DPP9.

Design and synthesis of potent carboxylic acid DGAT1 inhibitors with high cell permeability.

A series of potent carboxylic acid DGAT1 inhibitors with high permeability were developed from a virtual screening hit. Strategies were employed to reduce Pgp substrate recognition and increase passive permeability, resulting in the discovery of a series showing good inhibition of cellular triglyceride synthesis. The mutagenic potential of prospective metabolites was evaluated in the Ames assay, and one aniline was shown to be devoid of mutagenicity.

A practical microreactor for electrochemistry in flow.

A microreactor for electrochemical synthesis has been designed and fabricated. It has been shown that different reactions can be carried out successfully using simple protocols.

Tethered aminohydroxylation: dramatic improvements to the process.

[reaction: see text] Changing the identity of the N leaving group on a hydroxylamine-based reoxidant gives a dramatic improvement to the tethered aminohydroxylation reaction. Using OCOC6F5 as a leaving group means that only 1 mol % of osmium is required and yields as high as 98% can be obtained. Acyclic homoallylic alcohols were substrates considered too unreactive for effective use in the tethered aminohydroxylation reaction; improved reaction conditions mean that they have now become viable substrates for oxidation.