Joel Gagnier

Improving the reporting of pragmatic trials: an extension of the CONSORT statement

Background The CONSORT statement is intended to improve reporting of randomised controlled trials and focuses on minimising the risk of bias (internal validity). The applicability of a trial’s results (generalisability or external validity) is also important, particularly for pragmatic trials. A pragmatic trial (a term first used in 1967 by Schwartz and Lellouch) can be broadly defined as a randomised controlled trial whose purpose is to inform decisions about practice. This extension of the CONSORT statement is intended to improve the reporting of such trials and focuses on applicability. Methods At two, two-day meetings held in Toronto in 2005 and 2008, we reviewed the CONSORT statement and its extensions, the literature on pragmatic trials and applicability, and our experiences in conducting pragmatic trials. Recommendations We recommend extending eight CONSORT checklist items for reporting of pragmatic trials: the background, participants, interventions, outcomes, sample size, blinding, participant flow, and generalisability of the findings. These extensions are presented, along with illustrative examples of reporting, and an explanation of each extension. Adherence to these reporting criteria will make it easier for decision makers to judge how applicable the results of randomised controlled trials are to their own conditions. Empirical studies are needed to ascertain the usefulness and comprehensiveness of these CONSORT checklist item extensions. In the meantime we recommend that those who support, conduct, and report pragmatic trials should use this extension of the CONSORT statement to facilitate the use of trial results in decisions about health care. Pragmatic trials are designed to inform decisions about practice, but poor reporting can reduce their usefulness. The CONSORT and Practihc groups describe modifications to the CONSORT guidelines to help readers assess the applicability of the results

Reporting Randomized, Controlled Trials of Herbal Interventions: An Elaborated CONSORT Statement

Randomized, controlled trials (RCTs) of herbal interventions often inadequately describe important aspects of their methods (1-4). Although the quality of reporting of these trials may be improving with time, many still lack important information, particularly about the composition of the herbal intervention (4, 5). Crude herbal drugs are natural products and their chemical composition varies depending on several factors, such as geographic source of the plant material, climate in which it was grown, and time of harvest. Commercially available herbal medicinal products also vary in their content and concentration of chemical constituents from batch to batch and when products containing the same herbal ingredient are compared among manufacturers (6-14). Even when herbal products are standardized for content of known active or marker compounds to achieve more consistent pharmaceutical quality, there is variation in the concentrations of other constituents. These variations can result in differences in pharmacologic activity in vitro (15) and in bioavailability in humans (16). Mindful of these issues, we elaborated on the 22-item checklist of the Consolidated Standards of Reporting Trials (CONSORT) statement (17) to help authors and editors improve reporting of RCTs of herbal interventions. Methods We developed these reporting recommendations in 3 phases that included premeeting item generation, a consensus meeting, and postmeeting feedback. The individuals who participated are listed in the Appendix. To generate items, 1 investigator conducted telephone interviews of 16 participants with expertise in the method and reporting of RCTs (5 participants), pharmacognosy (4 participants), herbal medicinal products (5 participants), medical statistics (1 participant), and herbal product manufacturing (1 participant). The investigator asked participants to suggest revisions to existing CONSORT checklist items and also to additional items required for reporting trials of herbal interventions. He asked participants to nominate revisions or new items on the basis of empirical evidence that not reporting the item would bias estimates of treatment effect. When no empirical evidence was available, commonsense reasoning was acceptable. After completing all telephone calls, the investigator thematically grouped items and circulated them by e-mail to each participant for review. Fourteen participants attended the consensus meeting. The meeting began with a review of the premeeting checklist item suggestions. We emphasized minimizing item elaborations and additions and basing elaborations on evidence whenever possible. Each item suggestion was presented and followed by debate for its inclusion, deletion, or modification. This process was repeated until all items were reviewed and a consensus emerged. After the consensus meeting, we circulated a draft summary report to all participants to ensure that it accurately represented decisions made during the consensus meeting. We then circulated the report to the wider CONSORT Group for input and revised it on the basis of their suggestions. Ethical approval was obtained from The University of Toronto Health Sciences Ethics Review Committee on 23 January 2004. Financial support for the consensus meeting was provided by the Canadian Institutes of Health Research. The funding body had no role in the design, conduct, or analysis of this study and did not influence the decision to submit the manuscript for publication. All researchers are independent of the funders. Results The group did not recommend any new CONSORT checklist items or modifications in the CONSORT flow diagram. We did, however, elaborate on 9 of the 22 CONSORT checklist items to enhance their relevance to trials of herbal interventions (Table, Figure; Appendix Table), including minor recommendations for 8 items (item 1 [title and abstract], item 2 [background], item 3 [participants], item 6 [outcomes], item 15 [baseline data], item 20 [interpretation], item 21 [generalizability], and item 22 [overall evidence]) and detailed recommendations for 1 item (item 4 [interventions]). Table. Proposed Elaboration of CONSORT Checklist Item 4 for Reporting Randomized, Controlled Trials of Herbal Medicine Interventions Figure. The high-pressure liquid chromatography chemical fingerprint for the extract of Ginkgo biloba L Appendix Table. Proposed Elaborations of CONSORT Items for Randomized, Controlled Trials of Herbal Medicine Interventions The Table shows the detailed recommendations for item 4 and an example of good reporting related to each recommendation. These recommendations begin with the words where applicable to indicate that all information suggested may not be applicable to every type of herbal medicine intervention. For example, an herbal medicinal product comprising crude herbal material (for example, leaves and stems) simply prepared as a tea or decoction does not require description of the type and concentration of solvent used and the ratio of herbal drug to extract (item 4B.3). Also, not every herbal medicine intervention will have a finished product or extract name or manufacturer (item 4A.2), but instead may be made by the investigators specifically for the study. In such circumstances, all methods used in preparing and formulating the product must be reported. Similarly, item 4F is not required for herbal interventions when the practitioner is not a part of the intervention. With these exceptions, we recommend that all information shown in the Table be reported for all herbal interventions. Discussion We developed recommendations to be used in conjunction with the existing CONSORT checklist when reporting RCTs of herbal interventions. In particular, we thought it imperative that reports of RCTs provide clear and complete descriptions of the herbal intervention. We think that our recommendations might also be relevant for reporting herbal interventions in other research designs, whether preclinical (for example, in vivo or in vitro) or clinical (for example, N of 1 trials), and refer interested readers to a detailed explanatory document that further describes each of our recommendations and provides additional examples of good reporting (22). We hope that authors find our recommendations instructive and that journals will endorse their use and modify their instructions to authors accordingly.

The CARE guidelines: consensus-based clinical case report guideline development

BACKGROUND A case report is a narrative that describes, for medical, scientific, or educational purposes, a medical problem experienced by one or more patients. Case reports written without guidance from reporting standards are insufficiently rigorous to guide clinical practice or to inform clinical study design. PRIMARY OBJECTIVE Develop, disseminate, and implement systematic reporting guidelines for case reports. METHODS We used a three-phase consensus process consisting of (1) pre-meeting literature review and interviews to generate items for the reporting guidelines, (2) a face-to-face consensus meeting to draft the reporting guidelines, and (3) post-meeting feedback, review, and pilot testing, followed by finalization of the case report guidelines. RESULTS This consensus process involved 27 participants and resulted in a 13-item checklist-a reporting guideline for case reports. The primary items of the checklist are title, key words, abstract, introduction, patient information, clinical findings, timeline, diagnostic assessment, therapeutic interventions, follow-up and outcomes, discussion, patient perspective, and informed consent. CONCLUSIONS We believe the implementation of the CARE (CAse REport) guidelines by medical journals will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports will inform clinical study design, provide early signals of effectiveness and harms, and improve healthcare delivery.

A Systematic Review and Meta-Analysis of Efficacy, Cost-Effectiveness, and Safety of Selected Complementary and Alternative Medicine for Neck and Low-Back Pain

Background. Back pain is a common problem and a major cause of disability and health care utilization. Purpose. To evaluate the efficacy, harms, and costs of the most common CAM treatments (acupuncture, massage, spinal manipulation, and mobilization) for neck/low-back pain. Data Sources. Records without language restriction from various databases up to February 2010. Data Extraction. The efficacy outcomes of interest were pain intensity and disability. Data Synthesis. Reports of 147 randomized trials and 5 nonrandomized studies were included. CAM treatments were more effective in reducing pain and disability compared to no treatment, physical therapy (exercise and/or electrotherapy) or usual care immediately or at short-term follow-up. Trials that applied sham-acupuncture tended towards statistically nonsignificant results. In several studies, acupuncture caused bleeding on the site of application, and manipulation and massage caused pain episodes of mild and transient nature. Conclusions. CAM treatments were significantly more efficacious than no treatment, placebo, physical therapy, or usual care in reducing pain immediately or at short-term after treatment. CAM therapies did not significantly reduce disability compared to sham. None of the CAM treatments was shown systematically as superior to one another. More efforts are needed to improve the conduct and reporting of studies of CAM treatments.

Evidence of effectiveness of herbal medicinal products in the treatment of arthritis. Part 2: Rheumatoid arthritis

Herbal medicinal products (HMPs) are used in a variety of oral and topical forms for the treatment of osteoarthritis. The aim of this study was to update a previous systematic review published in 2000. We searched electronic databases (MEDLINE, EMBASE, CISCOM, AMED, CINAHL, Cochrane registers) to June 2007, unrestricted by date or language, and included randomized controlled trials that compared HMPs with inert (placebo) or active controls in patients with osteoarthritis. Five reviewers contributed to data extraction. Disagreements were discussed and resolved by consensus with reference to Cochrane guidelines and advice from the Cochrane Collaboration.

Interventions Designed to Prevent Anterior Cruciate Ligament Injuries in Adolescents and Adults A Systematic Review and Meta-analysis

Background: Anterior cruciate ligament (ACL) injuries are common, result in significant morbidity, and are expensive to repair surgically and to rehabilitate. Several randomized and observational studies have tested neuromuscular interventions as preventive measures for these injuries. Purpose: To conduct a systematic review and meta-analysis of all known comparative studies for estimating and testing the effect of neuromuscular and educational interventions on the incidence of ACL injuries in adolescents and adults, both male and female. Study Design: Systematic review and meta-analysis. Methods: Several databases were used to identify eligible studies through July 4, 2011: MEDLINE, EMBASE, SPORTDiscus, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Central Register of Controlled Trials, and Health Technology Assessment. Eligible studies were assessed for risk of bias, and meta-analyses were performed on the estimated intervention effect (log incidence rate ratio) using inverse-variance weighting, subgroup analysis, and random-effects meta-regression to estimate the overall (pooled) effect and explore heterogeneity of effect across studies (measured by I2 and tested with the Q statistic). Results: Eight cohort (observational) studies and 6 randomized trials were included, involving a total of approximately 27,000 participants. The random-effects meta-analysis yielded a pooled rate-ratio estimate of 0.485 (95% confidence interval [CI], 0.299-0.788; P = .003), indicating a lower ACL rate in the intervention groups, but there was appreciable heterogeneity of the estimated effect across studies (I2 = 64%; P = .001). In the meta-regressions, the estimated effect was stronger for studies that were not randomized, performed in the United States, conducted in soccer players, had a longer duration of follow-up (more than 1 season), and had more hours of training per week in the intervention group, better compliance, and no dropouts. Nevertheless, residual heterogeneity was still observed within subgroups of those variables (I2 > 50%; P < .10). Conclusion: The authors found that various types of neuromuscular and educational interventions appear to reduce the incidence rate of ACL injuries by approximately 50%, but the estimated effect varied appreciably among studies and was not able to explain most of that variability. Clinical Relevance: Neuromuscular and educational interventions appear to reduce the incidence rate of ACL injuries by approximately 50%.

Harpgophytum procumbens for osteoarthritis and low back pain: A systematic review

BackgroundThe objective of this review is to determine the effectiveness of Harpagophytum procumbens preparations in the treatment of various forms of musculoskeletal pain.MethodsSeveral databases and other sources were searched to identify randomized controlled trials, quasi-randomized controlled trials, and controlled clinical trials testing Harpagophytum preparations in adults suffering from pain due to osteoarthritis or low back pain.ResultsGiven the clinical heterogeneity and insufficient data for statistical pooling, trials were described in a narrative way, taking into consideration methodological quality scores. Twelve trials were included with six investigating osteoarthritis (two were identical trials), four low back pain, and three mixed-pain conditions.ConclusionsThere is limited evidence for an ethanolic Harpagophytum extract containing less than <30 mg harpagoside per day in the treatment of knee and hip osteoarthritis. There is moderate evidence of effectiveness for (1) the use of a Harpagophytum powder at 60 mg harpagoside in the treatment of osteoarthritis of the spine, hip and knee; (2) the use of an aqueous Harpagophytum extract at a daily dose of 100 mg harpagoside in the treatment of acute exacerbations of chronic non-specific low back pain; and (3) the use of an aqueous extract of Harpagophytum procumbens at 60 mg harpagoside being non-inferior to 12.5 mg rofecoxib per day for chronic non-specific low-back pain (NSLBP) in the short term. Strong evidence exists for the use of an aqueous Harpagophytum extract at a daily dose equivalent of 50 mg harpagoside in the treatment of acute exacerbations of chronic NSLBP.

Herbal medicine for low back pain : A cochrane review

Study Design. Systematic review of randomized controlled trials (RCTs). Objectives. To determine the effectiveness of herbal medicine for nonspecific low back pain (LBP). Summary of Background Data. Many people with chronic LBP use complementary and alternative medicine (CAM), visit CAM practitioners, or both. Several herbal medicines have been purported for use in treating people with LBP. This is an update of a Cochrane Review first published in 2006. Methods. We searched numerous electronic databases up to September 2014; checked reference lists in review articles, guidelines and retrieved trials; and personally contacted individuals with expertise in this area. We included RCTs examining adults (over 18 years of age) suffering from acute, sub-acute, or chronic nonspecific LBP. The interventions were herbal medicines that we defined as plants used for medicinal purposes in any form. Primary outcome measures were pain and function. Two review authors assessed risk of bias, GRADE criteria (GRADE 2004), and CONSORT compliance and a random subset were compared with assessments by a third individual. Two review authors assessed clinical relevance and resolved any disagreements by consensus. Results. Fourteen RCTs (2050 participants) were included. Capsicum frutescens (cayenne) reduces pain more than placebo. Although Harpagophytum procumbens (devils claw), Salix alba (white willow bark), Symphytum officinale L. (comfrey), Solidago chilensis (Brazilian arnica), and lavender essential oil also seem to reduce pain more than placebo, evidence for these substances was of moderate quality at best. No significant adverse events were noted within the included trials. Conclusions. Additional well-designed large trials are needed to test these herbal medicines against standard treatments. In general, the completeness of reporting in these trials was poor. Trialists should refer to the CONSORT statement extension for reporting trials of herbal medicine interventions. Level of Evidence: N/A

The CARE guidelines: consensus-based clinical case reporting guideline development

A case report is a narrative that describes, for medical, scientific or educational purposes, a medical problem experienced by one or more patients. Case reports written without guidance from reporting standards are insufficiently rigorous to guide clinical practice or to inform clinical study design. Develop, disseminate and implement systematic reporting guidelines for case reports. We used a three-phase consensus process consisting of (1) premeeting literature review and interviews to generate items for the reporting guidelines, (2) a face-to-face consensus meeting to draft the reporting guidelines and (3) postmeeting feedback, review and pilot testing, followed by finalisation of the case report guidelines. This consensus process involved 27 participants and resulted in a 13-item checklist—a reporting guideline for case reports. The primary items of the checklist are title, key words, abstract, introduction, patient information, clinical findings, timeline, diagnostic assessment, therapeutic interventions, follow-up and outcomes, discussion, patient perspective and informed consent. We believe the implementation of the CARE (CAse REport) guidelines by medical journals will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports will inform clinical study design, provide early signals of effectiveness and harms, and improve healthcare delivery.

Evidence of Effectiveness of Herbal Medicinal Products in the Treatment of Arthritis

Herbal medicinal products (HMPs) that interact with the mediators of inflammation are used in the treatment of rheumatoid arthritis (RA). The aim of this study was to update a previous systematic review published in 2000. We searched electronic databases (MEDLINE, EMBASE, CISCOM, AMED, CINAHL, Cochrane registers) to June 2007, unrestricted by date or language, and included randomized controlled trials that compared HMPs with inert (placebo) or active controls in patients with rheumatoid arthritis. Five reviewers contributed to data extraction. Disagreements were discussed and resolved by consensus with reference to Cochrane guidelines and advice from the Cochrane Collaboration.