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Biomedical subjects

Gordon H Guyatt

Publications and source records attributed to Gordon H Guyatt.

At least 19 recordsLinked to original sources
PubMed2007

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

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 beta-blocker). The main outcome, risk of shock therapy, was reduced when comparing amiodarone plus beta-blocker with beta-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 beta-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.

Anti-Arrhythmia Agents↗
PubMed2006

Combining scores from different patient reported outcome measures in meta-analyses: when is it justified?

BACKGROUND: Combining outcomes and the use of standardized effect measures such as effect size and standardized response mean across instruments allows more comprehensive meta-analyses and should avoid selection bias. However, such analysis ideally requires that the instruments correlate strongly and that the underlying assumption of similar responsiveness is fulfilled. The aim of the study was to assess the correlation between two widely used health-related quality of life instruments for patients with chronic obstructive pulmonary disease and to compare the instruments' responsiveness on a study level. METHODS: We systematically identified all longitudinal studies that used both the Chronic Respiratory Questionnaire (CRQ) and the St. George's Respiratory Questionnaire (SGRQ) through electronic searches of MEDLINE, EMBASE, CENTRAL and PubMed. We assessed the correlation between CRQ (scale 1-7) and SGRQ (scale 1-100) change scores and compared responsiveness of the two instruments by comparing standardized response means (change scores divided by their standard deviation). RESULTS: We identified 15 studies with 23 patient groups. CRQ change scores ranged from -0.19 to 1.87 (median 0.35, IQR 0.14-0.68) and from -16.00 to 3.00 (median -3.00, IQR -4.73-0.25) for SGRQ change scores. The correlation between CRQ and SGRQ change scores was 0.88. Standardized response means of the CRQ (median 0.51, IQR 0.19-0.98) were significantly higher (p < 0.001) than for the SGRQ (median 0.26, IQR -0.03-0.40). CONCLUSION: Investigators should be cautious about pooling the results from different instruments in meta-analysis even if they appear to measure similar constructs. Despite high correlation in changes scores, responsiveness of instruments may differ substantially and could lead to important between-study heterogeneity and biased meta-analyses.

Data Interpretation, Statistical↗
PubMed2006

How a well-grounded minimal important difference can enhance transparency of labelling claims and improve interpretation of a patient reported outcome measure.

The evaluation and use of patient reported outcome (PRO) measures requires detailed understanding of the meaning of the outcome of interest. The Food and Drug Administration (FDA) recently presented its draft guidance and view on the use of PRO measures as endpoints in clinical trials. One section of the guidance document specifically deals with advice about the use of the minimal important difference (MID) that we redefined as the smallest difference in score in the outcome of interest that informed patients or informed proxies perceive as important. The advice, however, is short, indeed much too short. We believe that expanding the section and making it more specific will benefit all stakeholders: patients, clinicians, other clinical decision makers, those designing trials and making claims, payers and the FDA. There is no "gold standard" methodology of estimating the MID or achieving the meaningfulness of clinical trial results based on patient reported outcomes. There are many methods of estimating the MID usually grouped into two distinct categories: anchor-based methods, that examine the relationship between scores on the target instrument and some independent measure, and distribution-based methods resorting to the statistical characteristics of the obtained scores. Estimation of an MID and interpretation of clinical trial results that present patient important outcomes is demanding but vital for informing the decision to recommend approve a given intervention. Investigators are encouraged to use reliable and valid methods to achieve meaningfulness of their results, preferably those that rely on patients to estimate what constitutes a minimal important, small, moderate, or large difference. However, acquiring the meaningfulness of PRO measures transcends beyond a concept of the MID and we advocate that dichotomizing the scores of patient-reported outcome measures facilitate interpretability of clinical trial results for those who need to understand trial results after a labelling claim has been granted. Irrespective of the strategy investigators use to estimate these values, from the individual patient perspective it is much more relevant if investigators report both the estimated thresholds and the proportion of patients achieving that benefit.

Clinical Trials as Topic↗
PubMed2006

Epidemiology and reporting of randomized trials employing re-randomization of patient groups: a systematic survey.

Trials employing re-randomization of some or all participants provide opportunities for determining optimal dosing and dosing schedules, potential disease modifying effects, direct comparisons between drugs, and salvage therapy for patients failing their assigned treatments. To date, no data exists about their prevalence, epidemiology, or quality. We undertook a systematic review of all trials re-randomizing patients. Using explicit search criteria, we searched 11 electronic databases independently, in duplicate. We additionally searched pharmaceutical company websites for unpublished studies. We extracted data on the epidemiology of trials, year published, characteristics of the purpose of the re-randomization, what groups of patients were re-randomized, and methodological issues, including allocation, concealment, sequence generation, blinding, intention to treat, and appropriate sample size calculations. We found 65 trials. All trials were reported in English. Of these, 21 employed re-randomization to determine optimal dosing, 8 for optimal dose-scheduling, 3 for salvage therapy, 0 for estimating disease modifying effects, 24 as direct comparison trials, 9 as standard efficacy trials--that did not require re-randomization, and 3 as withdrawal of treatment trials. The median sample size of the period prior to re-randomization is 180 [interquartile range (IQR) 83-480] and after re-randomization is 104 [IQR 36 to 246]. Studies lost a median of 8% of eligible patients from period 1 to period 2 [IQR 0 to 17]. Studies were published between 1975 and 2005, with the vast majority (71%) published since 1995. The findings of our review indicate that trials employing re-randomization are relatively rare, have poor reporting of important methodological features, and, in some circumstances, fail to take advantage of the benefits that re-randomization can permit.

Dose-Response Relationship, Drug↗
PubMed2006

Interpreting the results of patient reported outcome measures in clinical trials: the clinician's perspective.

This article deals with the problem of interpreting health-related quality of life (HRQL) outcomes in clinical trials. First, we will briefly describe how dichotomization and item response theory can facilitate interpretation. Based on examples from the medical literature for the interpretation of HRQL scores we will show that dichotomies may help clinicians understand information provided by HRQL instruments in RCTs. They can choose thresholds to calculate proportions of patients benefiting based on absolute scores or change scores. For example, clinicians interpreting clinical trial results could consider the difference in the proportion of patients who achieve a mean score of 50 before and after an intervention on a scale from 1 to 100. For the change score approach, they could consider the proportion of patients who have changed by a score of 5 or more. Finally, they can calculate the proportion of patients benefiting and transform these numbers into a number needed to treat or natural frequencies. Second, we will describe in more detail an approach to the interpretation of HRQL scores based on the minimal important difference (MID) and proportions. The MID is the smallest difference in score in the outcome of interest that informed patients or informed proxies perceive as important, either beneficial or harmful, and that would lead the patient or clinician to consider a change in the management. Any change in management will depend on the downsides, including cost and inconvenience, associated with the intervention. Investigators can help with the interpretation of HRQL scores by determining the MID of an HRQL instrument and provide mean differences in relation to the MID. For instance, for an MID of 0.5 on a seven point scale investigators could provide the mean change on the instrument as well as the proportion of patients with scores greater than the MID. Thus, there are several steps investigators can take to facilitate this process to help bringing HRQL information closer to the bedside.

Data Interpretation, Statistical↗
PubMed2006

Adherence to antiretroviral therapy in sub-Saharan Africa and North America: a meta-analysis.

CONTEXT: Adherence to antiretroviral therapy is a powerful predictor of survival for individuals living with human immunodeficiency virus (HIV) and AIDS. Concerns about incomplete adherence among patients living in poverty have been an important consideration in expanding the access to antiretroviral therapy in sub-Saharan Africa. OBJECTIVE: To evaluate estimates of antiretroviral therapy adherence in sub-Saharan Africa and North America. DATA SOURCES: Eleven electronic databases were searched along with major conference abstract databases (inclusion dates: inception of database up until April 18, 2006) for all English-language articles and abstracts; and researchers and treatment advocacy groups were contacted. Study Selection and Data Abstraction To best reflect the general population, studies of mixed populations in both North America and Africa were selected. Studies evaluating specific populations such as men only, homeless individuals, or drug users, were excluded. The data were abstracted in duplicate on study adherence outcomes, thresholds used to determine adherence, and characteristics of the populations. A random-effects meta-analysis was performed in which heterogeneity was examined using multivariable random-effects logistic regression. A sensitivity analysis was performed using Bayesian methods. DATA SYNTHESIS: Thirty-one studies from North America (28 full-text articles and 3 abstracts) and 27 studies (9 full-text articles and 18 abstracts) from sub-Saharan Africa were included. African studies represented 12 sub-Saharan countries. Of the North American studies, 71% used patient self-report to assess adherence; this was true of 66% of the African assessments. Studies reported similar thresholds for adherence monitoring (eg, 100%, >95%, >90%, >80%). A pooled analysis of the North American studies (17,573 patients total) indicated a pooled estimate of 55% (95% confidence interval, 49%-62%; I2, 98.6%) of the populations achieving adequate levels of adherence. Our pooled analysis of African studies (12,116 patients total) indicated a pooled estimate of 77% (95% confidence interval, 68%-85%; I2, 98.4%). Study continent, adherence thresholds, and study quality were significant predictors of heterogeneity. Bayesian analysis was used as an alternative statistical method for combining adherence rates and provided similar findings. CONCLUSION: Our findings indicate that favorable levels of adherence, much of which was assessed via patient self-report, can be achieved in sub-Saharan African settings and that adherence remains a concern in North America.

Africa South of the Sahara↗
PubMed2006

Analysis of the burden of treatment in patients receiving an EpiPen for yellow jacket anaphylaxis.

BACKGROUND: Venom immunotherapy (VIT) is a treatment with established efficacy for the prevention of repeated anaphylactic reactions in patients with Hymenoptera allergy, which also allows patients to discontinue carrying an EpiPen. Despite their merits, both treatments can have negative aspects potentially important to patients. OBJECTIVE: We examined possible negative aspects of the EpiPen in comparison with VIT as perceived by patients. METHODS: Positive and negative aspects of both treatments were measured by using a burden of treatment questionnaire together with statements about the EpiPen. RESULTS: One hundred ninety-three patients were included, of whom 94 consented to randomization: 47 received VIT, and 47 received the EpiPen. Of the remaining 99, 75 chose VIT, and 26 chose the EpiPen. Of the patients receiving VIT, 91.5% were (extremely) positive about their treatment, and 85% would choose VIT again. Of the patients receiving the EpiPen, only 48% were positive about their treatment, and even of these patients, 68% preferred to be treated with VIT after 1 year of carrying the EpiPen. Although most patients indicated that it is reassuring to carry an EpiPen and makes them feel safe, many patients also indicated that it is inconvenient and troublesome. Especially patients who were negative about the EpiPen indicated that they would not dare use the EpiPen if necessary and were afraid at possible side effects. CONCLUSION: In contrast to VIT, the EpiPen is perceived as burdensome by most patients with venom allergy. For most patients, an EpiPen is an unsuitable definitive treatment. CLINICAL IMPLICATIONS: As VIT enables patients with venom allergy to get rid of the EpiPen, patients should be offered VIT.

Adolescent↗
PubMed2006

Relative responsiveness of the Chronic Respiratory Questionnaire, St. Georges Respiratory Questionnaire and four other health-related quality of life instruments for patients with chronic lung disease.

BACKGROUND: Selection of heath-related quality of life (HRQL) instruments that are most responsive to changes in HRQL prevents investigators from drawing false-negative conclusions about the effectiveness of an intervention. The objective of this study was to compare the responsiveness of the Chronic Respiratory Questionnaire (CRQ), the St. Georges Respiratory Questionnaire (SGRQ) and four other HRQL instruments. METHODS: We enrolled 177 patients with chronic lung disease, primarily COPD (93%), who completed 8 weeks of respiratory rehabilitation. Patients completed the CRQ, the SGRQ and four generic measures (SF-36, Feeling Thermometer, Standard Gamble and Health Utilities index 3) at the beginning of the rehabilitation program and 12 weeks thereafter. We calculated standardized response means (SRMs) for each instrument, from the change score divided by the standard deviation of the change score. RESULTS: We observed the largest SRM for the CRQ (0.24-0.66 for the four CRQ domains on the interviewer-administered and 0.56-0.84 for the self-administered format) and the SGRQ (0.33-0.51 for the three SGRQ domains and total score). The CRQ dyspnea domain was statistically significantly more responsive than any other instrument including the SGRQ. For the SGRQ, the total and impacts domain were significantly more responsive than the generic and preference-based instruments. CONCLUSIONS: This study confirms that the CRQ and SGRQ are substantially more responsive than generic measures, and suggests particularly strong responsiveness for the self-administered CRQ.

Aged↗
PubMed2006

Vasopressin or epinephrine for out-of-hospital cardiac arrest.

STUDY OBJECTIVE: The use of vasopressin in patients with cardiac arrest presenting with specific rhythms is controversial. We performed an evidence-based emergency medicine review of evidence comparing vasopressin to epinephrine in structured cardiac arrest protocols. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library, and other databases for randomized trials or systematic reviews comparing vasopressin to epinephrine for adults with cardiac arrest and measuring survival to hospital discharge and neurologic function in survivors. We used standard criteria to appraise the quality of published trials and systematic reviews. We used the random effects model in supplementary analyses to summarize results and to test for significant differences across subgroups of patients presenting with different arrest rhythms. RESULTS: We found 3 high-quality well-reported randomized trials and 1 rigorous meta-analysis. The evidence does not confirm a consistent benefit of vasopressin over epinephrine in increasing survival or improving neurologic outcome in survivors. Subgroup analysis reveals a large difference in effect of vasopressin over epinephrine in cardiac arrest patients with asystole, compared to other arrest rhythms, coming from within-trial comparisons. The difference is not consistent across otherwise similar trials, is not statistically significant, may reflect the application of multiple unplanned subgroup analyses, and is not supported by a plausible biological hypothesis. CONCLUSION: Evidence from randomized trials does not establish a benefit of vasopressin over epinephrine in increasing survival to discharge or improving neurologic outcomes in adult patients with nontraumatic cardiac arrest.

Brain Damage, Chronic↗
PubMed2006

Can contraindications compromise evidence-based, patient-centered clinical practice?

BACKGROUND: Despite their often weak evidence base, contraindications convey the unequivocally adverse risk-benefit profile of an intervention in a specific clinical context. However, some patients in that context may nonetheless prefer the contraindicated intervention (with its potential benefits and risks) to the available alternatives. The impact of contraindications on treatment decisions remains unexplored. OBJECTIVE: To provide an estimate of the impact of the "contraindication" label on treatment decisions. METHODS: We conducted an international 6-wave email/internet and fax survey of practicing clinicians who were members of the American Diabetes Association or the College of Physicians and Surgeons of Ontario and had available email addresses and fax numbers. Each participant considered one of two patient scenarios. In each scenario, the patient expressed a strong preference for use of a medication that carried a "contraindication" label despite weak evidence of harm. We designed these scenarios so that respondents who placed greater weight on patient preferences and research evidence than on the label "contraindication" would be ready to prescribe the contraindicated medication. We determined the frequency with which the label "contraindication" dominated participants' treatment decisions despite patient preferences and weak evidence of harm. RESULTS: 466 participants responded (22% response rate). Depending on the group and scenario, contraindications dominated the decisions of 47% to 89% of surveyed clinicians, superseding patient preferences and research evidence. CONCLUSIONS: The label "contraindication" may often dominate clinicians' decisions about treatment and may compromise evidence-based, patient-centered clinical practice. Further research should elucidate the process that leads to the formulation of contraindications and its impact on treatment decision-making.

Attitude of Health Personnel↗
PubMed2006

Do clinical marker states improve responsiveness and construct validity of the standard gamble and feeling thermometer: a randomized multi-center trial in patients with chronic respiratory disease.

BACKGROUND: Optimizing the validity and responsiveness of utility measures will enhance their usefulness in randomized trials. We evaluated the impact of clinical marker state (CMS) rating prior to patients' rating their own health on two utility instruments (feeling thermometer (FT) and standard gamble (SG)) in patients with chronic respiratory disease (CRD). METHODS: We randomized 182 patients with CRD to complete the FT (self-administered) and SG with CMS (FT+/SG+, n=91) or without marker states (FT-/SG-, n=91) before and after undergoing respiratory rehabilitation in a multi-center trial. RESULTS: Use of CMS did not influence baseline utility scores. Improvement after therapy on the scale from 0 (dead) to 1.0 (full health) was 0.04 both in FT+ (p=0.03) and FT- (p=0.02; the difference between FT+ and FT- was 0.00, p=0.83). Improvement on the SG was 0.05 in both SG+ (p=0.08) and SG- (p=0.04; difference between SG+ and SG- 0.00, p=0.95). Correlations with other health related quality of life scores were highest for FT+. CONCLUSION: Administration of CMS did not improve responsiveness of the FT but may have improved construct validity. The SG showed limited construct validity and responsiveness that was not influenced by CMS use.

Aged↗
PubMed2006

Rationale, design, and organization of the PeriOperative ISchemic Evaluation (POISE) trial: a randomized controlled trial of metoprolol versus placebo in patients undergoing noncardiac surgery.

BACKGROUND: Noncardiac surgery is associated with significant cardiovascular mortality, morbidity, and cost. Small trials of beta-blockers suggest that they may prevent cardiovascular events in patients undergoing noncardiac surgery, but trial results are inconclusive. We have initiated the POISE trial to definitively establish the effects of beta-blocker therapy in patients undergoing noncardiac surgery. METHODS: The POISE trial is a blinded, randomized, and controlled trial of controlled-release metoprolol versus placebo in 10000 patients at risk for a perioperative cardiovascular event who are undergoing noncardiac surgery. Patients will receive the study drug 2 to 4 hours before surgery and subsequently for 30 days. The primary outcome is a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal cardiac arrest at 30 days. Patients will also be followed for events at 1 year. RESULTS: To date, the POISE trial has recruited >6300 patients in 182 centers in 21 countries. Currently, the patients' mean age is 69 years; 63% are males, 43% have a history of coronary artery disease, 43% have a history of peripheral arterial disease, and 30% have diabetes. Most participants have undergone vascular (42%), intraabdominal (23%), or orthopedic (19%) surgery. CONCLUSIONS: The POISE trial is a large international trial that will provide a reliable assessment of the effects of beta-blocker therapy in patients undergoing noncardiac surgery.

Adrenergic beta-Antagonists↗
PubMed2006

Impact of pulmonary rehabilitation on psychosocial morbidity in patients with severe COPD.

STUDY OBJECTIVE: To assess the effect of pulmonary rehabilitation (PR) on psychosocial morbidity, functional exercise capacity, and health-related quality of life (HRQL) in patients with severe COPD. DESIGN: A prospective, randomized, controlled trial with blinding of outcome assessment and data analysis. SETTING: A tertiary-care respiratory service. PATIENTS: Forty patients (mean age, 65 +/- 8 years [+/- SD]) with severe chronic flow limitation (FEV(1), 35 +/- 13%) without respiratory failure (Pao(2), 72 +/- 9 mm Hg; Paco(2), 42 +/- 5 mm Hg) were randomized either to a control group or to a PR group (PRG). INTERVENTIONS: Sixteen weeks of PR that included breathing retraining and exercise. MEASUREMENTS: At baseline and 16 weeks, we evaluated psychosocial morbidity using two questionnaires (the Millon Behavior Health Inventory [MBHI] and the Revised Symptom Checklist [SCL-90-R]) and measured 6-min walk distance (6WMD) and HRQL using the Chronic Respiratory Questionnaire (CRQ). RESULTS: We found differences in favor of the PRG in the following MBHI domains: introversive, forceful, and sensitive personality styles (all p </= 0.05) and chronic tension (p </= 0.01). Results of the depression, hostility, global severity, positive symptom distress index (all p </= 0.01), somatization, anxiety, psychoticism, and positive symptom (all p </= 0.05) domains of the SCL-90-R favored the PRG. We also found statistically and clinically significant differences between groups in 6MWD (85 m; p < 0.01) and in two domains of the CRQ: dyspnea (1.0; p < 0.01) and mastery (0.6; p < 0.05). The other two domains of CRQ showed strong trends in favor of PRG: 0.7 for both fatigue and emotional function (minimal important difference, 0.5). CONCLUSIONS: PR may decrease psychosocial morbidity in COPD patients even when no specific psychological intervention is performed. Findings from this study also confirm the positive impact of PR on functional exercise capacity and HRQL.

Aged↗
PubMed2005

Randomized trials stopped early for benefit: a systematic review.

CONTEXT: Randomized clinical trials (RCTs) that stop earlier than planned because of apparent benefit often receive great attention and affect clinical practice. Their prevalence, the magnitude and plausibility of their treatment effects, and the extent to which they report information about how investigators decided to stop early are, however, unknown. OBJECTIVE: To evaluate the epidemiology and reporting quality of RCTs involving interventions stopped early for benefit. DATA SOURCES: Systematic review up to November 2004 of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify RCTs stopped early for benefit. STUDY SELECTION: Randomized clinical trials of any intervention reported as having stopped early because of results favoring the intervention. There were no exclusion criteria. DATA EXTRACTION: Twelve reviewers working independently and in duplicate abstracted data on content area and type of intervention tested, reporting of funding, type of end point driving study termination, treatment effect, length of follow-up, estimated sample size and total sample studied, role of a data and safety monitoring board in stopping the study, number of interim analyses planned and conducted, and existence and type of monitoring methods, statistical boundaries, and adjustment procedures for interim analyses and early stopping. DATA SYNTHESIS: Of 143 RCTs stopped early for benefit, the majority (92) were published in 5 high-impact medical journals. Typically, these were industry-funded drug trials in cardiology, cancer, and human immunodeficiency virus/AIDS. The proportion of all RCTs published in high-impact journals that were stopped early for benefit increased from 0.5% in 1990-1994 to 1.2% in 2000-2004 (P<.001 for trend). On average, RCTs recruited 63% (SD, 25%) of the planned sample and stopped after a median of 13 (interquartile range [IQR], 3-25) months of follow-up, 1 interim analysis, and when a median of 66 (IQR, 23-195) patients had experienced the end point driving study termination (event). The median risk ratio among truncated RCTs was 0.53 (IQR, 0.28-0.66). One hundred thirty-five (94%) of the 143 RCTs did not report at least 1 of the following: the planned sample size (n = 28), the interim analysis after which the trial was stopped (n = 45), whether a stopping rule informed the decision (n = 48), or an adjusted analysis accounting for interim monitoring and truncation (n = 129). Trials with fewer events yielded greater treatment effects (odds ratio, 28; 95% confidence interval, 11-73). CONCLUSIONS: RCTs stopped early for benefit are becoming more common, often fail to adequately report relevant information about the decision to stop early, and show implausibly large treatment effects, particularly when the number of events is small. These findings suggest clinicians should view the results of such trials with skepticism.

Clinical Trials Data Monitoring Committees↗