Literature update December 2009

Joel E. Tepper and A. William Blackstock. Randomized Trials and Technology Assessment. Ann Intern Med 2009; 151:583-584.

Aaron L. Nelson, Joshua T. Cohen, Dan Greenberg, and David M. Kent. Much Cheaper, Almost as Good: Decrementally Cost-Effective Medical Innovation. Ann Intern Med 2009; 151:662-667.

Under conditions of constrained resources, cost-saving innovations may improve overall outcomes, even when they are slightly less effective than available options, by permitting more efficient reallocation of resources. The authors systematically reviewed all MEDLINE-cited cost– utility analyses written in English from 2002 to 2007 to identify and describe cost- and quality-decreasing medical innovations that might offer favorable “decrementally” cost-effective tradeoffs—defined as saving at least $100 000 per quality-adjusted life-year lost. Of 2128 cost effectiveness ratios from 887 publications, only 9 comparisons (0.4% of total) described 8 innovations that were deemed to be decrementally cost-effective. Examples included percutaneous coronary intervention (instead of coronary artery bypass graft) for multivessel coronary disease, repetitive transcranial magnetic stimulation (instead of electroconvulsive therapy) for drug-resistant major depression, watchful waiting for inguinal hernias, and hemodialyzer sterilization and reuse. On a per-patient basis, these innovations yielded savings from $122 to almost $12 000 but losses of 0.001 to 0.021 quality-adjusted life-years (approximately 8 hours to 1 week). These findings demonstrate the rarity of decrementally cost-effective innovations in the medical literature.

Amy Folkes, Robin Urquhart, Eva Grunfeld. Are leading medical journals following their own policies on CONSORT reporting? Contemporary Clinical Trials 2008;29(6): 843-846.

The revised Consolidated Standards of Reporting Trials (CONSORT) statement recognizes the importance of including data so that readers are able to judge the reliability or relevance of randomized controlled trial (RCT) findings. However, it is unclear whether journals consistently report the pre-randomization information necessary to assess the general applicability of trial results. The objective of this study was to assess the extent of adherence to pre-randomization data reporting in 4 leading general medicine journals, as recommended by the revised CONSORT statement over a specific time frame. A total of 480 RCTs met the eligibility criteria for review. In 2004, 138 of 246 (56%) articles reported the full CONSORT pre-randomization information, of which 121 (88%) presented this information in diagram form. In 2006, 136 of 234 (58%) reported the full information, of which 127 (93%) presented the information in a diagram. These numbers indicate no improvement in the reporting of pre-randomization information. In conclusion, reporting of the full CONSORT data remains inconsistent. We recommend that journals continue to support the CONSORT statement and ensure that adequate information is provided upon submission before commencing the peer review process. The presentation of clear, precise data will ensure that readers are able to better interpret the applicability of findings.

Tazeen H. Jafar, Juanita Hatcher, Neil Poulter, Muhammad Islam, Shiraz Hashmi, Zeeshan Qadri et al. Community-Based Interventions to Promote Blood Pressure Control in a Developing Country: A Cluster Randomized Trial. Ann Intern Med 2009; 151:593-601.

Background: Despite convincing evidence that lowering blood pressure decreases cardiovascular morbidity and mortality, the hypertension burden remains high and control rates are poor in developing countries. Objective: To assess the effectiveness of 2 community-based interventions on blood pressure in hypertensive adults.

Design: Cluster randomized, 2 × 2 factorial, controlled trial. (ClinicalTrials.gov registration number: NCT00327574).

Setting: 12 randomly selected communities in Karachi, Pakistan. Patients: 1341 patients 40 years or older with hypertension (systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or already receiving treatment).

Measurements: Reduction in systolic blood pressure from baseline to end of follow-up at 2 years. Intervention: Family-based home health education (HHE) from lay health workers every 3 months and annual training of general practitioners (GPs) in hypertension management.

Results: The age, sex, and baseline blood pressure–adjusted decrease in systolic blood pressure was significantly greater in the HHE and GP group (10.8 mm Hg [95% CI, 8.9 to 12.8 mm Hg]) than in the GP-only, HHE-only, or no intervention groups (5.8 mm Hg [CI, 3.9 to 7.7 mm Hg] in each; P < 0.001). The interaction between the main effects of GP training and HHE on the primary outcome approached significance (interaction P = 0.004 in intention-to-treat analysis and P = 0.044 in per-protocol analysis). Limitations: Follow-up blood pressure measurements were missing for 22% of patients. No mechanism was detected by which interventions lowered blood pressure.

Conclusion: Family-based HHE delivered by trained lay health workers, coupled with educating GPs on hypertension, can lead to significant blood pressure reductions among patients with hypertension in Pakistan. Both strategies in combination may be feasible for upscaling within the existing health care systems of Indo-Asian countries.

M Lugtenberg, J S Burgers, G P Westert. Effects of evidence-based clinical practice guidelines on quality of care: a systematic review. Qual Saf Health Care 2009;18:385-392 doi:10.1136/qshc.2008.028043

Background: Evidence-based clinical guidelines aim to improve the quality of care. In The Netherlands, considerable time and effort have been invested in the development and implementation of evidence-based guidelines since the 1990s. Thus far, no reviews are available on their effectiveness. The primary aim of this article was to assess the evidence for the effectiveness of Dutch evidence-based clinical guidelines in improving the quality of care.

Methods: A systematic review of studies evaluating the effects of Dutch evidence-based guidelines on both the process and structure of care and patient outcomes was conducted. The electronic databases Medline and Embase (1990–2007) and relevant scientific journals were searched. Studies were only selected if they included a controlled trial, an interrupted time series design or a before and after design. Results: A total of 20 studies were included. In 17 of 19 studies that measured the effects on the process or structure of care, significant improvements were reported. Thirteen of these studies reported improvement with respect to some of the recommendations studied. In addition, the size of the observed effects varied largely across the recommendations within guidelines. Six of nine studies that measured patient health outcomes showed significant but small improvements as a result of the use of clinical guidelines.

Conclusions: This review demonstrates that Dutch evidence-based clinical guidelines can be effective in improving the process and structure of care. The effects of guidelines on patient health outcomes were studied far less and data are less convincing. The high level of variation in effects across recommendations suggests that implementation strategies tailored to individual recommendations within the guideline are needed to establish relevant improvements in healthcare. Moreover, the results highlight the need for well-designed studies focusing on the level of the recommendations to determine which factors influence guideline utilisation and improved patient outcomes.

Margaret B. Harrison, France Légaré, Ian D. Graham, Béatrice Fervers. Adapting clinical practice guidelines to local context and assessing barriers to their use. CMAJ 2009.DOI:10.1503/cmaj.081232

Heejung Bang, Alison M. Edwards, Andrew S. Bomback, Christie M. Ballantyne, David Brillon, Mark A. Callahan et al. Development and
Validation of a Patient Self-assessment Score for Diabetes Risk. Ann Intern Med 2009;151:775-783.

Background: National guidelines disagree on who should be screened for undiagnosed diabetes. No existing diabetes risk score is highly
generalizable or widely followed. Objective: To develop a new diabetes screening score and compare it with other available screening instruments (Centers for Disease Control and Prevention, American Diabetes Association, and U.S. Preventive Services Task Force guidelines; 2 American Diabetes Association risk questionnaires; and the Rotterdam model).

Design: Cross-sectional data. Setting: NHANES (National Health and Nutrition Examination Survey) 1999 to 2004 for model development and 2005 to 2006, plus a combined cohort of 2 community studies, ARIC (Atherosclerosis Risk in Communities) Study and CHS (Cardiovascular Health Study), for validation.

Participants: U.S. adults aged 20 years or older.

Measurements: A risk-scoring algorithm for undiagnosed diabetes, defined as fasting plasma glucose level of 7.0 mmol/L (126 mg/dL) or greater without known diabetes, was developed in the development data set. Logistic regression was used to determine which participant characteristics were independently associated with undiagnosed diabetes. The new algorithm and other methods were evaluated by standard diagnostic and feasibility measures.

Results: Age, sex, family history of diabetes, history of hypertension, obesity, and physical activity were associated with undiagnosed diabetes. In NHANES (ARIC/CHS), the cut-point of 5 or more points selected 35% (40%) of persons for diabetes screening and yielded a sensitivity of 79% (72%), specificity of 67% (62%), positive predictive value of 10% (10%), and positive likelihood ratio of 2.39 (1.89). In contrast, the comparison scores yielded a sensitivity of 44% to 100%, specificity of 10% to 73%, positive predictive value of 5% to 8%, and positive likelihood ratio of 1.11 to 1.98. Limitation: Data during pregnancy were not available.

Conclusion: This easy-to implement diabetes screening score seems to demonstrate improvements over existing methods. Studies are needed to evaluate it in diverse populations in real-world settings.

Amit X Garg, Arthur V Iansavichus, Nancy L Wilczynski, Monika Kastner, Leslie A Baier, Salimah Z Shariff et al. Filtering Medline for a clinical discipline: diagnostic test assessment framework. BMJ 2009;339:b3435.

Objective: To develop and test a Medline filter that allows clinicians to search for articles within a clinical discipline, rather than searching the entire Medline database.

Design: Diagnostic test assessment framework with development and validation phases.

Setting: Sample of 4657 articles published in 2006 from 40 journals.

Reviews: Each article was manually reviewed, and 19.8% contained information relevant to the discipline of nephrology. The performance of 1 155 087 unique renal filters was compared with the manual review. Main outcome measures Sensitivity, specificity, precision, and accuracy of each filter.

Results: The best renal filters combined two to 14 terms or phrases and included the terms “kidney” with multiple endings (that is, truncation), “renal replacement therapy”, “renal dialysis”, “kidney function tests”, “renal”, “nephr” truncated, “glomerul” truncated, and “proteinuria”. These filters achieved peak sensitivities of 97.8% and specificities of 98.5%. Performance of filters remained excellent in the validation phase.

Conclusions: Medline can be filtered for the discipline of nephrology in a reliable manner. Storing these high performance renal filters in PubMed could help clinicians with their everyday searching. Filters can also be developed for other clinical disciplines by using similar methods.

Jeffrey M Drazen, Martin B Van Der Weyden, Paush Sahni, Jacob Rosenberg, Ana Marusic, Christine Laine et al. Disclosure of competing
interests. BMJ 2009;339:b4144.

John P.A. Ioannidis. Integration of evidence from multiple meta-analyses: a primer on umbrella reviews, treatment networks and multiple treatments meta-analyses. CMAJ 2009 181: 488-493.

MaryAnn Foote. Backing Up Your Statements: How To Perform Literature Searches To Prove Your Points. Chest 2009;136:1432-1434;
doi:10.1378/chest.09-1615

Jared A. Blum, Kalev Freeman, Richard C. Dart, Richelle J. Cooper. Requirements and Definitions in Conflict of Interest Policies of Medical Journals. JAMA. 2009;302(20):2230-2234.

Context: Conflicts of interest (COIs) may influence medical literature. However, it is unclear whether medical journals have consistent policies for defining and soliciting COI disclosures.

Objective: To determine the prevalence of author COI policies, requirements for signed disclosure statements, and variability in COI definitions among medical journals.

Design: A cross-sectional survey of Instructions for Authors and manuscript submission documents, including authorship responsibility forms, for high-impact medical journals across 35 subject categories available from March through October 2008.

Main Outcome Measure: Presence of language referring to COI disclosure in the Instructions for Authors or manuscript submission documents.

Results: Of 256 journals, 89% had author COI policies. Fifty-four percent required authors to sign a disclosure statement, and 77% provided definitions of COI. Most definitions were limited to direct financial relationships; a minority of journals requested disclosure of other potential conflicts such as personal relationships (42%), paid expert testimony (42%), relationships with other organizations (26%), or travel grants (12%). The prevalence of policies varied by subject category: all internal medicine, respiratory medicine, and toxicology journals studied had comprehensive COI definitions, with 19 of these 24 journals requiring signed disclosure attestations. In contrast, 6 of 19 geriatrics, radiology, and rehabilitation journals requested author COI disclosure. Most journals that officially endorsed International Committee of Medical Journal Editors guidelines had COI policies (68/69), compared with 84% of journals not endorsing the guidelines (158/187).

Conclusions: In 2008, most medical journals with relatively high impact factors had author COI policies available for public review. Among journals, there was substantial variation in policies for solicitation of author COIs and in definitions of COI.