Showing papers by "Gordon H. Guyatt published in 2007"

Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials

Abstract: Objective To explore the extent to which components of composite end points in randomised controlled trials vary in importance to patients, the frequency of events in the more and less important components, and the extent of variability in the relative risk reductions across components. Design Systematic review of randomised controlled trials. Data sources Cardiovascular randomised controlled trials published in the Lancet, Annals of Internal Medicine , Circulation , European Heart Journal, JAMA , and New England Journal of Medicine , from 1 January 2002 to 30 June 2003. Component end points of composite end points were categorised according to importance to patients as fatal, critical, major, moderate, or minor. Results Of 114 identified randomised controlled trials that included a composite end point of importance to patients, 68% (n=77) reported complete component data for the primary composite end point; almost all (98%; n=112) primary composite end points included a fatal end point. Of 84 composite end points for which component data were available, 54% (n=45) showed large or moderate gradients in both importance to patients and magnitude of effect across components. When analysed by categories of importance to patients, the most important components were associated with lower event rates in the control group (medians of 3.3-3.7% for fatal, critical, and major outcomes; 12.3% for moderate outcomes; and 8.0% for minor outcomes). Components of greater importance to patients were associated with smaller treatment effects than less important ones (relative risk reduction of 8% for death and 33% for components of minor importance to patients). Conclusion The use of composite end points in cardiovascular trials is frequently complicated by large gradients in importance to patients and in magnitude of the effect of treatment across component end points. Higher event rates and larger treatment effects associated with less important components may result in misleading impressions of the impact of treatment.

Helping patients with type 2 diabetes mellitus make treatment decisions: statin choice randomized trial.

Abstract: Background Poor quality of information transfer about the benefits and risks of statin drug use may result in patients not making informed decisions that they can act on in a timely fashion. Methods The effect of a decision aid about statin drugs on treatment decision making in 98 patients with diabetes was determined in a cluster randomized trial of decision aid vs control pamphlet, with concealed allocation, blinding of participants to study goals, and adherence to the intention-to-treat principle. Twenty-one endocrinologists conducted specialty outpatient metabolic consultations. Patients in the intervention group received Statin Choice , a tailored decision aid that presents the estimated 10-year cardiovascular risk, the absolute risk reduction with use of statin drugs, and the disadvantages of using statin drugs. Patients in the control group received the institution's pamphlet about cholesterol management. We measured acceptability, knowledge about options and cardiovascular risk, and decisional conflict immediately after the visit, and adherence to pill taking was measured 3 months later. Results Patients favored using the decision aid (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.2-6.9); patients who received the decision aid (n = 52) knew more (difference, 2.4 of 9 points; 95% CI, 1.5-3.3), had better estimated cardiovascular risk (OR, 22.4; 95% CI, 5.9-85.6) and potential absolute risk reduction with statin drugs (OR, 6.7; 95% CI, 2.2-19.7), and had less decisional conflict (difference, −10.6; 95% CI, −15.4 to −5.9 on a 100-point scale) than did patients in the control group (n = 46). Of 33 patients in the intervention group taking statin drugs at 3 months, 2 reported missing 1 dose or more in the last week compared with 6 of 29 patients in the control group taking statin drugs (OR, 3.4; 95% CI, 1.5-7.5). Conclusions A decision aid enhanced decision making about statin drugs and may have favorably affected drug adherence. Trial Registration clinicaltrials.gov Identifier:NCT00217061

Measuring parental perceptions of child oral health-related quality of life.

Abstract: Objectives The aim of this study was to develop and evaluate the P-CPQ, a measure of parental/caregiver perceptions of the oral health-related quality of life of children This forms one component of the Child Oral Health Quality of Life Questionnaire (COHQOL) Methods An item pool was developed through a review of existing child health questionnaires and interviews with parents/caregivers of children with pedodontic, orthodontic, and orofacial conditions The resulting 47 items were used in a study in which 208 parents/caregivers provided data on their frequency and importance The 31 items rated the most frequent and important were selected for the final questionnaire (P-CPQ) The P-CPQ validity and reliability were assessed by a new sample of 231 parents, 79 of whom completed two copies for the assessment of test-retest reliability Results The P-CPQ discriminated among the three clinical groups included in the expected direction Within-group analyses using clinical data provided some evidence that scores were associated with the severity of the condition The P-CPQ also showed good construct validity It had excellent internal consistency reliability with a Cronbach's alpha of 094 and demonstrated perfect test-retest reliability (ICC=085) Conclusion The study provides data to indicate that the P-CPQ is valid and reliable

Ethical Issues in Stopping Randomized Trials Early Because of Apparent Benefit

Abstract: Stopping randomized trials early because of an apparent benefit is becoming more common. To protect and promote the interests of trial participants, investigators may feel obligated to stop a trial early because of the apparent benefit of a study treatment (compared with placebo or other treatment). There are, however, serious ethical problems with doing so. Truncated trials systematically overestimate treatment effects; in cases where the number of accrued outcome events is small, the overestimation may be very large. Generating seriously inflated estimates of treatment effect violates the ethical research requirement of scientific validity. Subsequent use of inflated estimates to inform clinical decision making and practice guidelines violates the ethical requirements of social value and a favorable risk-benefit ratio. Researchers should ensure that a large number of outcome events accrues before stopping a trial and then continue recruitment to assess whether positive trends continue. This can balance the need to protect research participants with the ethical requirements of scientific validity, social value, and a favorable risk-benefit ratio.

Effect of Oxygen on Health Quality of Life in Patients with Chronic Obstructive Pulmonary Disease with Transient Exertional Hypoxemia

Abstract: Rationale: Ambulatory oxygen improves acute exercise performance in people with chronic obstructive pulmonary disease (COPD). This improvement may not translate into symptomatic benefit for patients during activities of daily living.Objectives: We undertook a series of individual randomized controlled trials (N-of-1 RCTs) to measure the effect of oxygen in patients with COPD who do not meet criteria for mortality reduction with long-term oxygen therapy.Methods: Twenty-seven patients completed blinded N-of-1 RCTs, each comprising three pairs of 2-week home treatment periods, with oxygen provided during one period of each pair and a placebo mixture during the other.Measurements and Main Results: Patients completed the Chronic Respiratory Questionnaire (CRQ), the St. George's Respiratory Questionnaire, and a home five-minute-walk test at the end of each period. We defined a positive response as a CRQ dyspnea score greater (less dyspnea) on oxygen than placebo during all three pairs of treatment periods, with...

Oxygen therapy during exercise training in chronic obstructive pulmonary disease.

Abstract: Background Exercise training within the context of pulmonary rehabilitation improves outcomes of exercise capacity, dyspnea and health-related quality of life in individuals with chronic obstructive pulmonary disease (COPD). Supplemental oxygen in comparison to placebo increases exercise capacity in patients performing single-assessment exercise tests. The addition of supplemental oxygen during exercise training may enable individuals with COPD to tolerate higher levels of activity with less exertional symptoms, ultimately improving quality of life. Objectives To determine how supplemental oxygen in comparison to control (compressed air or room air) during the exercise-training component of a pulmonary rehabilitation program affects exercise capacity, dyspnea and health-related quality of life in individuals with COPD. Search methods All records in the Cochrane Airways Group Specialized Register of trials coded as 'COPD' were searched using the following terms: (oxygen* or O2*) AND (exercis* or train* or rehabilitat* or fitness* or physical* or activ* or endur* or exert* or walk* or cycle*). Searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, EMBASE and CINAHL databases identified studies. The last search was carried out in June 2009. Selection criteria Only randomized controlled trials (RCTs) comparing oxygen-supplemented exercise training to non-supplemented exercise training (control group) were considered for inclusion. Participants were 18 years or older, diagnosed with COPD and did not meet criteria for long-term oxygen therapy. No studies with mixed populations (pulmonary fibrosis, cystic fibrosis, etc) were included. Exercise training was greater than or equal to three weeks in duration and included a minimum of two sessions a week. Data collection and analysis Two review authors independently selected trials for inclusion in the review and extracted data. Weighted mean differences (WMD) with 95% confidence intervals (CI) were calculated using a random-effects model. Missing data were requested from authors of primary studies. Main results Five RCTs met the inclusion criteria. The maximum number of studies compared in the meta-analysis was three (31 on oxygen versus 32 control participants), because all included studies did not measure the same outcomes. When two studies were pooled, statistically significant improvements of oxygen-supplemented exercise training were found in constant power exercise time, WMD 2.68 minutes (95% CI 0.07 to 5.28 minutes). Supplemental oxygen increased the average exercise time from 6 to 14 minutes; the control intervention increased average exercise time from 6 to 12 minutes. Constant power exercise end-of-test Borg score (on a scale from 1 to 10) also showed statistically significant improvements with oxygen-supplemented exercise training, WMD -1.22 units (95% CI -2.39 to -0.06). One study showed a significant improvement in the change of Borg score after the shuttle walk test, by -1.46 units (95% CI -2.72 to -0.19). There were no significant differences in maximal exercise outcomes, functional exercise outcomes (six-minute walk test), shuttle walk distance, health-related quality of life or oxygenation status. According to the GRADE system most outcomes were rated as low quality because they were limited by study quality. Authors' conclusions This review provides little support for oxygen supplementation during exercise training for individuals with COPD, but the evidence is very limited. Studies with larger number of participants and strong design are required to permit strong conclusions, especially for functional outcomes such as symptom alleviation, health-related quality of life and ambulation.

How can quality of life researchers make their work more useful to health workers and their patients

Abstract: To make optimal use of data from randomized trials in clinical decision-making, clinicians require knowledge of the magnitude of treatment effects. Reports of trials including quality of life data often fail to report results that provide interpretable estimates of magnitude of effect. Strategies that investigators could use to remedy this problem include reporting mean differences between groups in relation to the minimal important difference and reporting the proportion of patients who benefit from treatment and the associated number needed to treat. Techniques are available that allow investigators to use the same strategies in reporting pooled estimates from meta-analyses, even when studies use different instruments to measure the same construct. These reporting approaches, as well as ensuring access to data from individual items, will also help those developing decision aids to use quality of life data.

A systematic review of studies comparing health outcomes in Canada and the United States.

Abstract: Background: Differences in medical care in the United States compared with Canada, including greater reliance on private funding and for-profit delivery, as well as markedly higher expenditures, may result in different health outcomes. Objectives: To systematically review studies comparing health outcomes in the United States and Canada among patients treated for similar underlying medical conditions. Methods: We identified studies comparing health outcomes of patients in Canada and the United States by searching multiple bibliographic databases and resources. We masked study results before determining study eligibility. We abstracted study characteristics, including methodological quality and generalizability. Results: We identified 38 studies comparing populations of patients in Canada and the United States. Studies addressed diverse problems, including cancer, coronary artery disease, chronic medical illnesses and surgical procedures. Of 10 studies that included extensive statistical adjustment and enrolled broad populations, 5 favoured Canada, 2 favoured the United States, and 3 showed equivalent or mixed results. Of 28 studies that failed one of these criteria, 9 favoured Canada, 3 favoured the United States, and 16 showed equivalent or mixed results. Overall, results for mortality favoured Canada (relative risk 0.95, 95% confidence interval 0.92–0.98, p = 0.002) but were very heterogeneous, and we failed to find convincing explanations for this heterogeneity. The only condition in which results consistently favoured one country was end-stage renal disease, in which Canadian patients fared better. Interpretation: Available studies suggest that health outcomes may be superior in patients cared for in Canada versus the United States, but differences are not consistent.

The pylorus: take it or leave it? Systematic review and meta-analysis of pylorus-preserving versus standard whipple pancreaticoduodenectomy for pancreatic or periampullary cancer.

Abstract: Our objective was to determine the relative effects of pylorus-preserving pancreaticoduodenectomy (PPPD) and standard Whipple pancreaticoduodenectomy (SWPD) in patients with pancreatic or periampullary cancer. We searched seven bibliographic databases, conference proceedings, and reference lists of articles and textbooks, and we contacted experts in the field of hepatobiliary surgery. We included published and unpublished randomized controlled trials. We evaluated the methodological quality of trials and, in duplicate, extracted data regarding operative, perioperative, and long-term outcomes. We contacted all authors and asked them to provide additional information regarding the trials. We pooled results from the studies by using a random-effects model, evaluated the degree of heterogeneity, and explored potential explanations for heterogeneity. Six trials that included a total of 574 patients met eligibility criteria. In the pooled analysis, PPPD was 72 minutes faster (P < .001, 95% confidence interval [95% CI], 53–92), with 284 mL less blood loss (P < .001, 95% CI, 176–391) and .66 fewer units of blood transfused (P = .002, 95% CI, .25–1.16). Other perioperative and long-term outcomes did not statistically differ, although the confidence intervals include important differences. Moderate-quality evidence suggests PPPD is a faster procedure with less blood loss compared with SWPD. Large absolute differences in other key outcomes are unlikely; excluding relatively small differences will, however, require larger, methodologically stronger trials.

Adjunctive antiarrhythmic drug therapy in patients with implantable cardioverter defibrillators: a systematic review.

Abstract: Aims To assess the efficacy and safety of adjunctive antiarrhythmic drug therapy for preventing implantable cardioverter defibrillator (ICD) therapies. Methods and results We conducted a systematic literature search to identify all randomized, controlled trials assessing the efficacy of adjunctive antiarrhythmic drug therapy. Trial data were reviewed and extracted independently by two investigators in an unblinded, standardized manner. Eight trials including a total of 1889 patients were analysed. There was heterogeneity in the type of antiarrhythmic used in the treatment arm (amiodarone, sotalol, azimilide, and dofetilide) as well as in the control group (five trials compared with placebo and three trials compared with β-blocker). The main outcome, risk of shock therapy, was reduced when comparing amiodarone plus β-blocker with β-blocker alone (HR 0.27; 95% CI 0.14–0.52) and when comparing sotalol with placebo (HR 0.55; 95% CI 0.4–0.78). The effect was not conclusive when comparing sotalol with other β-blocker (HR 0.61; 95% CI 0.37–1) and azimilide or dofetilide with placebo (HR 0.78; 95% CI 0.58–1.04 and HR 0.67; 95% CI 0.43–1.04, respectively). Although there were some benefits for secondary outcomes in all antiarrhythmics, the magnitude of the benefit was higher with amiodarone. Conclusion Amiodarone is the most effective treatment to reduce ICD shock therapies. The benefit of other antiarrhythmics is limited to secondary outcomes.

Waking up from the DREAM of preventing diabetes with drugs

Abstract: The current epidemic of diabetes makes a drug to prevent it attractive. But despite promotion of recent research evidence, Victor Montori, William Isley, and Gordon Guyatt argue that we are not there yet

Cooling for neonatal hypoxic ischemic encephalopathy: do we have the answer?

Abstract: The neonatal community deserves congratulations for responding vigorously to Silverman's1 call for randomized controlled trials (RCTs) to evaluate neonatal therapies. Although more trials are still needed,2 existing RCTs present new challenges in interpretation. One of the most vexing is when to proclaim innovative therapies as “standard of care.” The neonatal critical care community faces this challenge in evaluation of hypothermia as treatment for hypoxemic-ischemic encephalopathy (HIE).3–5 National bodies have made declarations that the neonatal community should consider hypothermia experimental pending completion of current ongoing trials.6–9 Although the influence of these bodies is considerable, individual physicians and sites apparently feel pressure to “do something” in the very dire circumstances of HIE in the newborn. In an informal sample of convenience, we have found that some centers are performing cooling, either with or without informed consent. Although many clinicians concur with the leading bodies that state there is a need for additional trials, it is confusing for practicing neonatologists when some members of these bodies also publicly state that they are actively providing cooling therapy. If leading centers are promoting active cooling, they have, in effect, adopted cooling as a standard of care. This may not only have legal implications but also raises ethical issues for those who believe the right thing to do currently is to continue performing RCTs. The countervailing argument is that to not offer cooling as standard therapy for such a devastating disease as HIE is itself, unethical. These opposing viewpoints are not easily resolvable except by considering what the overall benefit of eliminating residual doubt, one way or the other, would be. Our concern is that advocacy of hypothermia as a standard of care represents an excessively low threshold for accepting promising therapies and will ultimately lead to resources … Address correspondence to Haresh Kirpalani, BM, MSc, Division of Neonatology, Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104. E-mail: kirpalanih{at}email.chop.edu

Naturopathic Care for Chronic Low Back Pain: A Randomized Trial

Abstract: Objective Chronic low back pain represents a substantial cost to employers through benefits coverage and days missed due to incapacity. We sought to explore the effectiveness of Naturopathic care on chronic low back pain.

The Work Productivity and Activity Impairment Questionnaire for Patients with Gastroesophageal Reflux Disease (WPAI-GERD) Responsiveness to Change and English Language Validation

Abstract: Background A validated productivity questionnaire, the Work Productivity and Activity Impairment questionnaire for Gastroesophageal Reflux Disease (WPAIGERD), exists for Swedish patients with GERD.

A decision aid for COPD patients considering inhaled steroid therapy: development and before and after pilot testing.

Abstract: Decision aids (DA) are tools designed to help patients make specific and deliberative choices among disease management options. DAs can improve the quality of decision-making and reduce decisional conflict. An area not covered by a DA is the decision of a patient with chronic obstructive pulmonary disease (COPD) to use inhaled steroids which requires balancing the benefits and downsides of therapy. We developed a DA for COPD patients considering inhaled steroid therapy using the Ottawa Decision Support Framework, the best available evidence for using inhaled steroid in COPD and the expected utility model. The development process involved patients, pulmonologists, DA developers and decision making experts. We pilot tested the DA with 8 COPD patients who completed an evaluation questionnaire, a knowledge scale, and a validated decisional conflict scale. The DA is a computer-based interactive tool incorporating four different decision making models. In the first part, the DA provides information about COPD as a disease, the different treatment options, and the benefits and downsides of using inhaled steroids. In the second part, it coaches the patient in the decision making process through clarifying values and preferences. Patients evaluated 10 out of 13 items of the DA positively and showed significant improvement on both the knowledge scale (p = 0.008) and the decisional conflict scale (p = 0.008). We have developed a computer-based interactive DA for COPD patients considering inhaled steroids serving as a model for other DAs in COPD, in particular related to inhaled therapies. Future research should assess the DA effectiveness.

Impact of short evidence summaries in discharge letters on adherence of practitioners to discharge medication. A cluster-randomised controlled trial

Abstract: Background: International concern about quality of medical care has led to intensive study of interventions to ensure care is consistent with best evidence. Simple, inexpensive, feasible and effective interventions remain limited. Objective: We examined the impact of one-sentence evidence summaries appended to consultants’ letters to primary care practitioners on adherence of the practitioners to recommendations made by the consultants regarding medication for patients with chronic medical problems. Design: Cluster-randomised trial. Setting: Secondary/primary care interface (urban district hospital/referral practices). Participants: 178 practices received one or more discharge letters with evidence summaries. The 66 practices in the intervention group provided feedback on 172 letters, and the 56 practices in the control group provided feedback on 96 letters. Results: Appending an evidence summary to discharge letters resulted in a decrease in non-adherence to discharge medication from 29.6% to 18.5% (difference adjusted for underlying medical condition 12.5%; p = 0.039). Among the five possible reasons for discontinuing discharge medication, the evidence summaries seemed to have the largest impact on budget-related reasons for discontinuation (2.6% in the intervention versus 10.7% in the control group (p = 0.052)). Most clinicians (72%) were enthusiastic about continuing receiving evidence summaries with discharge letters in routine care. Conclusions: The one-sentence evidence summary is a simple, inexpensive, well-accepted intervention that may improve primary care practitioners’ adherence to evidence-based consultant recommendations.

Allergy, and Immunology Physicians/American College of Asthma, American College of Chest Therapy: Evidence-Based Guidelines: Device Selection and Outcomes of Aerosol

Abstract: 2005;127;335-371 Chest Rajiv Dhand, Joseph L. Rau, Gerald C. Smaldone and Gordon Guyatt Myrna B. Dolovich, Richard C. Ahrens, Dean R. Hess, Paula Anderson, Allergy, and Immunology Physicians/American College of Asthma, American College of Chest : * Therapy: Evidence-Based Guidelines Device Selection and Outcomes of Aerosol http://chestjournal.chestpubs.org/content/127/1/335.full.html services can be found online on the World Wide Web at: The online version of this article, along with updated information and C1.html http://chestjournal.chestpubs.org/content/suppl/2005/01/19/127.1.335.D Supplemental material related to this article is available at: ISSN:0012-3692 ) http://chestjournal.chestpubs.org/site/misc/reprints.xhtml ( written permission of the copyright holder. this article or PDF may be reproduced or distributed without the prior Dundee Road, Northbrook, IL 60062. All rights reserved. No part of Copyright2005by the American College of Chest Physicians, 3300 Physicians. It has been published monthly since 1935. is the official journal of the American College of Chest Chest

Prokinetic drug utility in the treatment of gastroesophageal reflux esophagitis: a systematic review of randomized controlled trials

Abstract: Background: Esophagitis caused by gastroesophageal reflux disease (GERD) results in appreciable morbidity and economic burden. No systematic review has addressed the effectiveness of prokinetic drugs in the treatment of GERD esophagitis in adults. Objective: To determine the utility of prokinetic drugs in improving symptoms and endoscopic lesions in patients with GERD esophagitis. Methods: We included randomized controlled trials that compared prokinetic drugs with placebo. A systematic search included the Cochrane Controlled Trial Register, MEDLINE, CINAHL, LILACS, EMBASE, a manual search of books and article references, and contact with pharmaceutical companies. Reviewers assessed methodological quality and extracted data that were combined using a random effects model. Results: Eighteen articles met the eligibility criteria; of these, 13 used prokinetic drugs alone, 4 tested prokinetic drugs as additional therapy in patients receiving histamine-2 receptor blockers, and 1 tested them in patients receiving proton pump inhibitors. Seven studies evaluated clinical improvement only, 5 addressed endoscopic improvement only, and 6 reported both outcomes. Four studies failed to provide adequate data for pooling; 3 of the 4 reported results that suggested symptomatic benefit with prokinetic agents. Nine studies (379 patients) that provided the required data suggested a higher incidence of clinical improvement with prokinetic drugs versus placebo (relative risk [RR] 1.70, 95% confidence interval [CI] 1.37–2.12, heterogeneity p = 0.47, I 2 = 0%). Clinical improvement occurred in 53 out of 175 patients (30%) of the control group; applying the relative risk of 1.70 and associated confidence interval suggests that absolute increases in patients improved might vary from 18% to 41% (number needed to treat approximately 3 to 6). Improvement was similar in 4 studies in which the prokinetic agent was added to an antisecretory drug. The funnel plot, however, suggests the possibility of publication bias. Eleven studies (887 patients) suggested a higher likelihood of endoscopic improvement or healing esophagitis with prokinetic drugs (RR 1.26, 95% CI 1.03–1.53) but with significant heterogeneity (heterogeneity p = .05, I 2 = 46.2%) that we couldn’t explain with an a priori hypothesis. When we evaluated endoscopic healing as the main outcome we observed a trend toward better results in the treatment group, also with inexplicable heterogeneity (RR 1.36, CI 95% 0.97–1.89, I 2 = 61%). Conclusions: Randomized controlled trials provide moderate-quality evidence that prokinetic drugs improve symptoms in patients with reflux esophagitis and low-quality evidence that they have an impact on endoscopic healing.

[Patient reported outcomes: general principles of development and interpretability].

Abstract: Direct measurement of how people are feeling and the extent to which they are functioning in daily activities (generally as patient reported outcomes) is critical to judging the benefit of health interventions in chronic conditions Selection of an appropriate instrument will reflect a comprehensive understanding of the condition of interest and a thorough knowledge of the expected benefits and harms of the proposed intervention We provide a brief discussion about different ways that health and health measurement have been defined, including the International Classification of Function, Disability and Health (ICF), Health Related Quality of Life (HRQOL) and cost-to-benefit analyses We outline important properties (reliability, validity, and responsiveness) that a measurement instrument must demonstrate depending on the purpose of measurement, and provide insight as to how to interpret the results of studies that report patient reported outcomes