Victor M. Montori

CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials

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.

Testosterone Therapy in Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline

OBJECTIVE Our objective was to update the guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men published previously in 2006. PARTICIPANTS The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. CONCLUSIONS We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. We suggest the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. We recommend confirmation of the diagnosis by repeating the measurement of morning total testosterone and, in some men in whom total testosterone is near the lower limit of normal or in whom SHBG abnormality is suspected by measurement of free or bioavailable testosterone level, using validated assays. We recommend testosterone therapy for men with symptomatic androgen deficiency to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density. We recommend against starting testosterone therapy in patients with breast or prostate cancer, a palpable prostate nodule or induration or prostate-specific antigen greater than 4 ng/ml or greater than 3 ng/ml in men at high risk for prostate cancer such as African-Americans or men with first-degree relatives with prostate cancer without further urological evaluation, hematocrit greater than 50%, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms with International Prostate Symptom Score above 19, or uncontrolled or poorly controlled heart failure. When testosterone therapy is instituted, we suggest aiming at achieving testosterone levels during treatment in the mid-normal range with any of the approved formulations, chosen on the basis of the patients preference, consideration of pharmacokinetics, treatment burden, and cost. Men receiving testosterone therapy should be monitored using a standardized plan.

GRADE guidelines: 9. Rating up the quality of evidence.

The most common reason for rating up the quality of evidence is a large effect. GRADE suggests considering rating up quality of evidence one level when methodologically rigorous observational studies show at least a two-fold reduction or increase in risk, and rating up two levels for at least a five-fold reduction or increase in risk. Systematic review authors and guideline developers may also consider rating up quality of evidence when a dose-response gradient is present, and when all plausible confounders or biases would decrease an apparent treatment effect, or would create a spurious effect when results suggest no effect. Other considerations include the rapidity of the response, the underlying trajectory of the condition, and indirect evidence.

The Diagnosis of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline

OBJECTIVE The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushings syndrome. PARTICIPANTS The Task Force included a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. CONSENSUS PROCESS Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Societys CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage the Task Force incorporated needed changes in response to written comments. CONCLUSIONS After excluding exogenous glucocorticoid use, we recommend testing for Cushings syndrome in patients with multiple and progressive features compatible with the syndrome, particularly those with a high discriminatory value, and patients with adrenal incidentaloma. We recommend initial use of one test with high diagnostic accuracy (urine cortisol, late night salivary cortisol, 1 mg overnight or 2 mg 48-h dexamethasone suppression test). We recommend that patients with an abnormal result see an endocrinologist and undergo a second test, either one of the above or, in some cases, a serum midnight cortisol or dexamethasone-CRH test. Patients with concordant abnormal results should undergo testing for the cause of Cushings syndrome. Patients with concordant normal results should not undergo further evaluation. We recommend additional testing in patients with discordant results, normal responses suspected of cyclic hypercortisolism, or initially normal responses who accumulate additional features over time.

GRADE guidelines: 4. Rating the quality of evidence—study limitations (risk of bias)

In the GRADE approach, randomized trials start as high-quality evidence and observational studies as low-quality evidence, but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias. Well-established limitations of randomized trials include failure to conceal allocation, failure to blind, loss to follow-up, and failure to appropriately consider the intention-to-treat principle. More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results. Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance. Risk of bias may vary across outcomes (e.g., loss to follow-up may be far less for all-cause mortality than for quality of life), a consideration that many systematic reviews ignore. In deciding whether to rate down for risk of bias--whether for randomized trials or observational studies--authors should not take an approach that averages across studies. Rather, for any individual outcome, when there are some studies with a high risk, and some with a low risk of bias, they should consider including only the studies with a lower risk of bias.

Internet-based learning in the health professions:a meta-analysis

CONTEXT The increasing use of Internet-based learning in health professions education may be informed by a timely, comprehensive synthesis of evidence of effectiveness. OBJECTIVES To summarize the effect of Internet-based instruction for health professions learners compared with no intervention and with non-Internet interventions. DATA SOURCES Systematic search of MEDLINE, Scopus, CINAHL, EMBASE, ERIC, TimeLit, Web of Science, Dissertation Abstracts, and the University of Toronto Research and Development Resource Base from 1990 through 2007. STUDY SELECTION Studies in any language quantifying the association of Internet-based instruction and educational outcomes for practicing and student physicians, nurses, pharmacists, dentists, and other health care professionals compared with a no-intervention or non-Internet control group or a preintervention assessment. DATA EXTRACTION Two reviewers independently evaluated study quality and abstracted information including characteristics of learners, learning setting, and intervention (including level of interactivity, practice exercises, online discussion, and duration). DATA SYNTHESIS There were 201 eligible studies. Heterogeneity in results across studies was large (I(2) > or = 79%) in all analyses. Effect sizes were pooled using a random effects model. The pooled effect size in comparison to no intervention favored Internet-based interventions and was 1.00 (95% confidence interval [CI], 0.90-1.10; P < .001; n = 126 studies) for knowledge outcomes, 0.85 (95% CI, 0.49-1.20; P < .001; n = 16) for skills, and 0.82 (95% CI, 0.63-1.02; P < .001; n = 32) for learner behaviors and patient effects. Compared with non-Internet formats, the pooled effect sizes (positive numbers favoring Internet) were 0.10 (95% CI, -0.12 to 0.32; P = .37; n = 43) for satisfaction, 0.12 (95% CI, 0.003 to 0.24; P = .045; n = 63) for knowledge, 0.09 (95% CI, -0.26 to 0.44; P = .61; n = 12) for skills, and 0.51 (95% CI, -0.24 to 1.25; P = .18; n = 6) for behaviors or patient effects. No important treatment-subgroup interactions were identified. CONCLUSIONS Internet-based learning is associated with large positive effects compared with no intervention. In contrast, effects compared with non-Internet instructional methods are heterogeneous and generally small, suggesting effectiveness similar to traditional methods. Future research should directly compare different Internet-based interventions.

Conducting systematic reviews of diagnostic studies: didactic guidelines

BackgroundAlthough guidelines for critical appraisal of diagnostic research and meta-analyses have already been published, these may be difficult to understand for clinical researchers or do not provide enough detailed information.MethodsDevelopment of guidelines based on a systematic review of the evidence in reports of systematic searches of the literature for diagnostic research, of methodological criteria to evaluate diagnostic research, of methods for statistical pooling of data on diagnostic accuracy, and of methods for exploring heterogeneity.ResultsGuidelines for conducting diagnostic systematic reviews are presented in a stepwise fashion and are followed by comments providing further information. Examples are given using the results of two systematic reviews on the accuracy of the urine dipstick in the diagnosis of urinary tract infections, and on the accuracy of the straight-leg-raising test in the diagnosis of intervertebral disc hernia.

Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline

OBJECTIVE The aim was to formulate practice guidelines for endocrine treatment of transsexual persons. EVIDENCE This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence, which was low or very low. CONSENSUS PROCESS Committees and members of The Endocrine Society, European Society of Endocrinology, European Society for Paediatric Endocrinology, Lawson Wilkins Pediatric Endocrine Society, and World Professional Association for Transgender Health commented on preliminary drafts of these guidelines. CONCLUSIONS Transsexual persons seeking to develop the physical characteristics of the desired gender require a safe, effective hormone regimen that will 1) suppress endogenous hormone secretion determined by the persons genetic/biologic sex and 2) maintain sex hormone levels within the normal range for the persons desired gender. A mental health professional (MHP) must recommend endocrine treatment and participate in ongoing care throughout the endocrine transition and decision for surgical sex reassignment. The endocrinologist must confirm the diagnostic criteria the MHP used to make these recommendations. Because a diagnosis of transsexualism in a prepubertal child cannot be made with certainty, we do not recommend endocrine treatment of prepubertal children. We recommend treating transsexual adolescents (Tanner stage 2) by suppressing puberty with GnRH analogues until age 16 years old, after which cross-sex hormones may be given. We suggest suppressing endogenous sex hormones, maintaining physiologic levels of gender-appropriate sex hormones and monitoring for known risks in adult transsexual persons.

GRADE guidelines: 5. Rating the quality of evidence—publication bias

In the GRADE approach, randomized trials start as high-quality evidence and observational studies as low-quality evidence, but both can be rated down if a body of evidence is associated with a high risk of publication bias. Even when individual studies included in best-evidence summaries have a low risk of bias, publication bias can result in substantial overestimates of effect. Authors should suspect publication bias when available evidence comes from a number of small studies, most of which have been commercially funded. A number of approaches based on examination of the pattern of data are available to help assess publication bias. The most popular of these is the funnel plot; all, however, have substantial limitations. Publication bias is likely frequent, and caution in the face of early results, particularly with small sample size and number of events, is warranted.

Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline

OBJECTIVE The aim was to formulate practice guidelines on the management of hyperglycemia in hospitalized patients in the non-critical care setting. PARTICIPANTS The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, six additional experts, and a methodologist. EVIDENCE This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society members, American Diabetes Association, American Heart Association, American Association of Diabetes Educators, European Society of Endocrinology, and the Society of Hospital Medicine reviewed and commented on preliminary drafts of this guideline. CONCLUSIONS Hyperglycemia is a common, serious, and costly health care problem in hospitalized patients. Observational and randomized controlled studies indicate that improvement in glycemic control results in lower rates of hospital complications in general medicine and surgery patients. Implementing a standardized sc insulin order set promoting the use of scheduled basal and nutritional insulin therapy is a key intervention in the inpatient management of diabetes. We provide recommendations for practical, achievable, and safe glycemic targets and describe protocols, procedures, and system improvements required to facilitate the achievement of glycemic goals in patients with hyperglycemia and diabetes admitted in non-critical care settings.