Creating a Program to Support Registering and Reporting Clinical Trials at Johns Hopkins University.

PROBLEM: The Food and Drug Administration Amendments Act of 2007 (FDAAA) and the National Institutes of Health (NIH) require that many clinical trials register and report results on ClinicalTrials.gov. Noncompliance with these policies denies research participants and scientists access to potentially relevant findings and could lead to monetary penalties or loss of funding. After discovering hundreds of potentially noncompliant trials affiliated with the institution, the Johns Hopkins University School of Medicine (JHUSOM) sought to develop a program to support research teams with registration and reporting requirements. APPROACH: JHUSOM conducted a baseline assessment of institutional compliance in 2015, launched the ClinicalTrials.gov Program in June 2016, and expanded the program to the Sidney Kimmel Comprehensive Cancer Center in April 2018. The program is innovative in its comprehensive approach, and it was among the first to bring a large number of trials into compliance. OUTCOMES: From September 2015 to September 2020, JHUSOM brought completed and ongoing trials into compliance with FDAAA and NIH policies and maintained almost perfect compliance for new trials. During this period, the proportion of trials potentially noncompliant with the FDAAA decreased from 44% (339/774) to 2% (32/1,304). NEXT STEPS: JHUSOM continues to develop and evaluate tools and procedures that facilitate trial registration and results reporting. In collaboration with other academic medical centers, JHUSOM plans to share resources and to identify and disseminate best practices. This report identifies practical lessons for institutions that might develop similar programs.

Evaluation of quality of pharmacoeconomic studies involved in traditional Chinese medicine in China.

OBJECTIVES: The pharmacoeconomic studies of traditional Chinese medicine (TCM) are still in its infancy. Assessing the quality of pharmacoeconomic studies of TCM to improve the efficiency of health resource allocation and guide the rational use of medicine. METHODS: Four databases were searched from inception to January 2018. The Consolidated Health Economic Evaluation Reporting Standards statement (CHEERS) and the Quality of Health Economic Studies (QHES) were used to assess the reporting quality and methodological quality. STATA 12.0 and Meta analyst 3.13 were used to analyze the related data. RESULTS: A total of 178 studies were included. The methodological evaluation of the study found that the total score of QHES was 47.85 ± 8.09. The report quality evaluation results found that many studies did not report comprehensive information, such as lack of detailed reports on abstracts, study perspectives, time frames, discount rates, model selection, but the titles, study background and location, and health results, resource and cost estimates, analysis methods, and heterogeneity analysis are reported in more detail. Six of the ten stratification factors have statistically significant differences. CONCLUSION: The overall quality of pharmacoeconomic studies of TCM is low, and further standardization and improvement are needed to obtain reliable study results.

The reporting quality and risk of bias of randomized controlled trials of acupuncture for migraine: Methodological study based on STRICTA and RoB 2.0.

OBJECTIVES: To investigate the reporting quality and risk of bias of randomized controlled trials (RCTs) of acupuncture for migraine, to facilitate and improve the quality of RCTs of acupuncture for migraine. METHODS: The Cochrane Library, PubMed and EMBASE were searched from inception to June 11, 2019 using a comprehensive search strategy. The reporting quality and risk of bias of included RCTs were independently evaluated by two investigators using STRICTA and RoB 2.0. Any disagreement was resolved by a third investigator. RESULTS: A total of 28 eligible RCTs were published in 24 academic journals from 1994 to 2018. Based on STRICTA, four sub-items including "details of other interventions'' (1/28, 4 %), "setting and context of treatment" (9/28, 32 %), "the extent to which treatment was varied" (11/28, 39 %), and "number of needle insertions per subject per session" (13/28, 46 %), showed low reporting quality. A total of 32 different outcomes were reported in 28 RCTs, and based on RoB 2.0, nine (9/28, 32 %) RCTs were judged to be high RoB, three of which were owing to deviations from intended interventions; 11(11/28, 39 %) RCTs elicited some concerns; and eight (8/28, 29 %) RCTs were low RoB for their outcomes. CONCLUSIONS: The reporting quality and risk of bias of RCTs of acupuncture for migraine remain suboptimal. Therefore, all stakeholders should make a contribution to improve the quality of RCTs of acupuncture for migraine using STRICTA and RoB 2.0, while not limiting this approach solely to studies on migraine, using STRICTA and RoB 2.0 tools.

Recommendations for Designing, Conducting and Reporting Observational Studies in Homeopathy.

BACKGROUND: Randomized placebo-controlled trials are considered to be the gold standard in clinical research and have the highest importance in the hierarchical system of evidence-based medicine. However, from the viewpoint of decision makers, due to lower external validity, practical results of efficacy research are often not in line with the huge investments made over decades. METHOD: We conducted a narrative review. With a special focus on homeopathy, we give an overview on cohort, comparative cohort, case-control and cross-sectional study designs and explain guidelines and tools that help to improve the quality of observational studies, such as the STROBE Statement, RECORD, GRACE and ENCePP Guide. RESULTS: Within the conventional medical research field, two types of arguments have been employed in favor of observational studies. First, observational studies allow for a more generalizable and robust estimation of effects in clinical practice, and if cohorts are large enough, there is no over-estimation of effect sizes, as is often feared. We argue that observational research is needed to balance the current over-emphasis on internal validity at the expense of external validity. Thus, observational research can be considered an important research tool to describe "real-world" care settings and can assist with the design and inform the results of randomised controlled trails. CONCLUSIONS: We present recommendations for designing, conducting and reporting observational studies in homeopathy and provide recommendations to complement the STROBE Statement for homeopathic observational studies.

Standards for preclinical research and publications in developmental anaesthetic neurotoxicity: expert opinion statement from the SmartTots preclinical working group.

In March 2019, SmartTots, a public-private partnership between the US Food and Drug Administration and the International Anesthesia Research Society, hosted a meeting attended by research experts, anaesthesia journal editors, and government agency representatives to discuss the continued need for rigorous preclinical research and the importance of establishing reporting standards for the field of anaesthetic perinatal neurotoxicity. This group affirmed the importance of preclinical research in the field, and welcomed novel and mechanistic approaches to answer some of the field's largest questions. The attendees concluded that summarising the benefits and disadvantages of specific model systems, and providing guidance for reporting results, would be helpful for designing new experiments and interpreting results across laboratories. This expert opinion report is a summary of these discussions, and includes a focused review of current animal models and reporting standards for the field of perinatal anaesthetic neurotoxicity. This will serve as a practical guide and road map for novel and rigorous experimental work.

A methodological review revealed that reporting of trials in manual therapy has not improved over time.

OBJECTIVE: The aim of this review was to evaluate a selection of major reporting aspects in manual therapy (MT) trials, before and after the publication of the CONSORT extension for nonpharmacological trials (CONSORTnpt) STUDY DESIGN AND SETTING: We randomly selected 100 MT trials published between 2000 and 2015 and divided them into a pre-CONSORTnpt (n = 50) and a post-CONSORTnpt (n = 50) group. We extracted data on relevant issues of internal validity, reliability, and description of interventions. Two authors extracted data independently. Percentages were used for descriptive analyses, and Fisher's exact test and the chi-square test were used for group comparisons. RESULTS: Six different types of MT interventions with up to 20 controls were analyzed. The most common populations/conditions studied were healthy subjects and subjects with lower back or neck pain. Over 70% of studies included multi-session interventions, and 42% of studies reported long-term followup. The only significant differences between groups were the inclusion of a flowchart diagram, the estimated effect size, precision descriptions, and the description of intervention procedures. CONCLUSION: Our findings suggest that trials in MT show poor reporting even after the availability of standardized guidelines.

Workshop Report: FDA Workshop on Improving Cardiotoxicity Assessment With Human-Relevant Platforms.

Given that cardiovascular safety concerns remain the leading cause of drug attrition at the preclinical drug development stage, the National Center for Toxicological Research of the US Food and Drug Administration hosted a workshop to discuss current gaps and challenges in translating preclinical cardiovascular safety data to humans. This white paper summarizes the topics presented by speakers from academia, industry, and government intended to address the theme of improving cardiotoxicity assessment in drug development. The main conclusion is that to reduce cardiovascular safety liabilities of new therapeutic agents, there is an urgent need to integrate human-relevant platforms/approaches into drug development. Potential regulatory applications of human-derived cardiomyocytes and future directions in employing human-relevant platforms to fill the gaps and overcome barriers and challenges in preclinical cardiovascular safety assessment were discussed. This paper is intended to serve as an initial step in a public-private collaborative development program for human-relevant cardiotoxicity tools, particularly for cardiotoxicities characterized by contractile dysfunction or structural injury.

CONSORT extension for reporting N-of-1 trials for traditional Chinese medicine (CENT for TCM) : Recommendations, explanation and elaboration.

BACKGROUND: N-of-1 trial is a desired and appropriate approach to assessing the efficacy and safety of traditional Chinese medicine (TCM) interventions. There have been an increasing number of N-of-1 trials for TCM published. However, a lack of preferred reporting guidance led in the general poor reporting quality of these trials. Due to the unique characteristics of TCM, the working group developed this CONSORT Extension for reporting N-of-1 Trials for Traditional Chinese Medicine (CENT for TCM) to assist TCM researchers in reporting N-of-1 trials for TCM. METHODS: We registered CENT for TCM at the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network (available at equator-network.org). The development was a comprehensive process through collection of the initial reporting items, two-round scientific Delphi consensus survey with 17 panelists, revision and formation of the final reporting checklist. RESULTS: The checklist includes 25 items within six domains, eight items in which were extended and elaborated on the items of the CENT 2015 checklist. Explanation of the items were listed adequately considering the nature of TCM, introducing the concept of TCM syndrome differentiation and TCM interventions. CONCLUSIONS: CENT for TCM can be used to assess the completeness of the reporting of N-of-1 trials for TCM. The working group expect that CENT for TCM could be a practical tool to enhance the comprehensiveness and transparency of the design, implementation and reporting of N-of-1 trials for TCM.

Reporting quality of 2014-2018 clinical practice guidelines on diabetes according to the RIGHT checklist.

OBJECTIVE: Reporting Items for Clinical Practice Guidelines (CPGs) in HealThcare (RIGHT) checklist was used as a tool to assess the reporting quality of 2014-2018 CPGs on diabetes treatment, aiming to promote the application of RIGHT and improve the reporting quality of future guidelines. METHODS: We searched Chinese Biomedical Literature Service System (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP database, Medline, Embase, Allied, and Complementary MEdicine Database (AMED), and Medlive and Google Scholar (Google academics), and collected published CPGs on diabetes with published date during 1st January, 2014 and 7th November, 2018. CPGs on diabetes issued since 2014 were included and filtered by two reviewers independently. Then the basic information extraction and RIGHT evaluation of the included CPG are carried out. RESULTS: A total of 34 guidelines were included, out of which 7 are for Chinese and 27 for other countries. Overall, basic information (domain 1) got the highest (64.66%) reporting rate, while financing and conflict-of-interest statements and management (domain 6) got the lowest (8.1%). For all guidelines, classification of guidelines (item 1c) was sufficiently reported, and description of the specific sources of funding for all stages of guideline development (item 18a) was not reported. For Chinese CPGs, financing and conflict-of-interest statements and management (domain 6) was most insufficiently reported, and only identification of guideline in the title (item 1a), corresponding information of the developer or author (item 4), description of basic epidemiology (item 5), and subgroup description (item 7b) out of 22 items were better reported than foreign guidelines. CONCLUSIONS: Overall, the CPGs on diabetes during 2014-2018 adhered to ~41% RIGHT checklist, of which Chinese CPGs adhered less than that of foreign guidelines. It is suggested that the RIGHT reporting checklist should be endorsed and used by CPG developers to ensure higher quality and adequate use of guidelines.

Reporting preclinical anesthesia study (REPEAT): Evaluating the quality of reporting in the preclinical anesthesiology literature.

Poor reporting quality may contribute to irreproducibility of results and failed 'bench-to-bedside' translation. Consequently, guidelines have been developed to improve the complete and transparent reporting of in vivo preclinical studies. To examine the impact of such guidelines on core methodological and analytical reporting items in the preclinical anesthesiology literature, we sampled a cohort of studies. Preclinical in vivo studies published in Anesthesiology, Anesthesia & Analgesia, Anaesthesia, and the British Journal of Anaesthesia (2008-2009, 2014-2016) were identified. Data was extracted independently and in duplicate. Reporting completeness was assessed using the National Institutes of Health Principles and Guidelines for Reporting Preclinical Research. Risk ratios were used for comparative analyses. Of 7615 screened articles, 604 met our inclusion criteria and included experiments reporting on 52 490 animals. The most common topic of investigation was pain and analgesia (30%), rodents were most frequently used (77%), and studies were most commonly conducted in the United States (36%). Use of preclinical reporting guidelines was listed in 10% of applicable articles. A minority of studies fully reported on replicates (0.3%), randomization (10%), blinding (12%), sample-size estimation (3%), and inclusion/exclusion criteria (5%). Statistics were well reported (81%). Comparative analysis demonstrated few differences in reporting rigor between journals, including those that endorsed reporting guidelines. Principal items of study design were infrequently reported, with few differences between journals. Methods to improve implementation and adherence to community-based reporting guidelines may be necessary to increase transparent and consistent reporting in the preclinical anesthesiology literature.

Memory at the Sharp End: The Costs of Remembering With Others in Forensic Contexts.

In many applied contexts where accurate and reliable information informs operational decision-making, emergency response resource allocation, efficient investigation, judicial process, and, ultimately, the delivery of justice, the costs of unfettered conversational remembering can be high. To date, research has demonstrated that conversations between co-witnesses in the immediate aftermath of witnessed events and co-witness retellings of witnessed events often impair both the quality and quantity of information reported subsequently. Given the largely negative impact of conversational remembering on the recall of both individual witnesses and groups of witnesses in this context, this review explores the reasons why these costs occur, the conditions under which costs are exacerbated, and how, in practical terms, the costs can be reduced in order to maximize the accuracy and completeness of witness accounts.

Assessing the methodological and reporting quality of network meta-analyses in Chinese medicine.

BACKGROUND: An increasing number of network meta-analyses (NMAs) in traditional Chinese medicine (TCM) have been published recently, but the quality of them was lack of assessment. This study aims to evaluate the methodological and reporting quality of NMAs in TCM. METHODS: Six electronic databases, including PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, China National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature Database (CBM) from inception to January 2018, were searched. NMAs of TCM were included. A measurement tool to assess the methodological quality of systematic reviews (AMSTAR) and the PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions (PRISMA-NMA) were used to assess the methodological and reporting quality of the included NMAs. RESULTS: A total of 40 NMAs, including 2535 randomized controlled trials (RCTs), were included. They were published between December 2012 and November 2017. The median score and interquartile range of methodological and reporting quality was 7 (6-8) and 22 (19.1-27.1). Serious methodological flaws existed in the following aspects: the status of publication (22.5%), a list of studies provided (0%), assessment of publication bias (37.5%), and conflicts of interest (12.5%). Several items need to be improved in reporting, especially for Protocol and registration (2.5%), Data items (22.5%), Risk of bias across studies (Methods section) (37.5%), Results of individual studies (27.5%), Risk of bias across studies (Results section) (40%), Results of additional analyses (35%), and Funding (15%). CONCLUSIONS: The methodological and reporting quality of NMAs in TCM is moderate. Identified shortcomings of published NMAs should be taken into consideration in further trainings of authors and editors of NMAs in TCM. Future researchers should be encouraged to apply PRISMA-NMA, and a recognized tool for the assessment of NMA methodology was wanted.

Reporting characteristics of case reports of acupuncture therapy with CARE guidelines.

OBJECTIVE: To investigate the reporting characteristics of case reports of acupuncture therapy with CAse Report (CARE) guidelines, and to explore the applicability of the guidelines for these case reports. METHODS: Case reports published from January 1, 2011 to December 31, 2013, were identified by searching PubMed and the China Biomedicine Database by using MeSH terms. Screening and data extraction of case reports were conducted by two independent researchers. Assessments based on CARE guidelines and data analysis were conducted by using Excel 2003 and RevMan 5.0. RESULTS: A total of 61 case reports published in 19 journals were identified, which involved 16 major types of diseases. Fifteen (24.6%) case reports declared no conflict of interests, and 5 (8.2%) reported funding sources. None of these case reports met all items of CARE guidelines, and only 6 subordinate items were fully reported among 50% of the case reports. Subgroup analysis indicated that case reports published in English or those that did not have competing interests had higher reporting quality. CONCLUSIONS: The reporting quality of case reports of acupuncture therapy is rather low. The reason might be a lack of awareness among authors and the poor dissemination of information regarding CARE guidelines in China. More evaluation studies are needed to promote and improve adherence to CARE guidelines. Moreover, an extended version of CARE guidelines should be developed for cases reports of special interventions such as acupuncture or adverse events caused by interventions.

Standards of Reporting Kampo Products (STORK) in research articles.

There had been no standardized rules for citing ethical Kampo products used in clinical trials in journal articles. Although the name of a Kampo manufacturer was described in 77.9% of research articles, the name and ratios of crude drug components of Kampo formulas were not described in 77.5% of these papers. Considering the importance of proper characterization of interventions in the Consolidated Standards of Reporting Trials (CONSORT) checklist, we hereby propose the use of the Standards of Reporting Kampo Products (STORK) website, http://mpdb.nibiohn.go.jp/stork, as a reference for Kampo products. This will provide an official source on the internet for verified information on individual Kampo formulations for citation purposes in clinical research articles.

Urgent need to improve the quality of case report in traditional Chinese medicine: Assessment on reporting quality of 3,417 cases.

OBJECTIVE: To survey the reporting quality of traditional Chinese medicine (TCM) case reports published in recent years and understand the common problems. The assessment results would lay the foundation for the development of recommendations for case report in Chinese medicine. METHODS: This survey determined the reporting quality of cases with Chinese herbal decoction, Chinese proprietary medicine, acupuncture, moxibustion and other traditional therapies published in 20 core medical journals of China by searching the China Academic Journals Full-text Database from 2006 to 2010. Fifty survey items in 16 domains were used to determine the reporting quality. One point was assigned to each item (Yes=1 point; No=0 point), and total score was 50 points. The domain of treatment was assessed independently, ranging from 2 to 9 items for different TCM interventions. RESULTS: The total of 1,858 case reports, covering 3,417 cases were included to analyze from 13 out of 20 core medical journals of China. There were 74.8% of them did not identify the nature of study in title, while 73.9% did not comprise an abstract. Incomplete reporting was found in discussions/ comment, and only 38.9% had made recommendations or take-away messages. Figures and tables were infrequently used. Three cases cited the full names of patients, but without declaring that any consent was obtained. Over 90% reported the symptoms and signs of TCM, and characteristics on tongue and pulse, but less than 50% did mention other medical history and diagnostic rationale. More than 90% treatments of the included cases were herbal decoction, with clear reporting on the ingredients and dosages. However, the reporting rate of the dosages of each ingredient was just 48.4%. Almost none reported the quality control of crude herbs, manufacturers and lot numbers of herbal proprietary medicine. Besides, advices and precautions on diet, emotions and living were rare to be illustrated. CONCLUSION: Systematic reporting recommendations are urged to develop for improving the contents and format of case reports in TCM.

STRICTA: is it time to do more?

BACKGROUND: In order to facilitate the completeness and transparency of reporting on randomized controlled trials undertaken using acupuncture interventions, a consensus group of international experts developed the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) in 2002. This reporting guideline was updated in 2010, and was applicable to a broader range of acupuncture research, including uncontrolled trials and case reports. Subsequent evaluations have noted limitations on the impact of STRICTA in the reporting quality of acupuncture trials, and the description of acupuncture details remains poor. Thus improvement in the efficacy of the STRICTA guidelines is called for. DISCUSSION: We explored the STRICTA guidelines from four aspects, including the development procedure, validity assessment, endorsement and adherence, and citation situation. Based upon these findings, we provided five potential suggestions for further development of STRICTA. SUMMARY: STRICTA are valid reporting guidelines based on robust methodology and scientific content. However specific implementation strategies including: updating the STRICTA checklist; improving the STRICTA reporting efficiency; consistency with implementing the "Instructions for authors" for journals; establishing global STRICTA research centers; and expanding the STRICTA website, are needed. Such strategies will improve their utilization and impact positively on the quality of reporting on acupuncture research outcomes.

Industry sponsorship and publication bias among animal studies evaluating the effects of statins on atherosclerosis and bone outcomes: a meta-analysis.

BACKGROUND: The effect that sponsorship has on publication rates or overall effect estimates in animal studies is unclear, though methodological biases are prevalent in animal studies of statins and there may be differences in efficacy estimates between industry and non-industry sponsored studies. In the present analysis, we evaluated the impact of funding source on publication bias in animal studies estimating the effect of statins on atherosclerosis and bone outcomes. METHODS: We conducted two independent systematic reviews and meta-analyses identifying animal studies evaluating the effect of statins on reducing the risk of atherosclerosis outcomes (n = 49) and increasing the likelihood of beneficial bone outcomes (n = 45). After stratifying the included studies within each systematic review by funding source, three separate analyses were employed to assess publication bias in these meta-analyses­funnel plots, Egger's Linear Regression, and the Trim and Fill methods. RESULTS: We found potential evidence of publication bias, primarily in non-industry sponsored studies. In all 3 assessments of publication bias, we found evidence of publication bias in non-industry sponsored studies, while in industry-sponsored studies publication bias was not evident in funnel plots and Egger's regression tests. We also found that inadequate reporting of sponsorship in animal studies is still exceedingly common. CONCLUSIONS: In meta-analyses assessing the effects of statins on atherosclerosis and bone outcomes in animal studies, we found evidence of publication bias, though small numbers of industry-sponsored studies limit the interpretation of the trim-and-fill results. This publication bias is more prominent in non-industry sponsored studies. Industry and non-industry funded researchers may have different incentives for publication. Industry may have a financial interest to publish all preclinical animal studies to maximize the success of subsequent trials in humans, whereas non-industry funded academics may prefer to publish high impact statistically significant results only. Differences in previously published effect estimates between industry- and non-industry sponsored animal studies may be partially explained by publication bias.