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T C Chalmers

Publications and source records attributed to T C Chalmers.

At least 37 records · Page 2Linked to original sources

The rational use of therapeutic drugs in the 21st century. Important lessons from cumulative meta-analyses of randomized control trials.

The use of randomized control trials to assess the usefulness of therapeutic drugs over the last half century has brought significant benefits to patient care. The full potential benefits, however, have been only partially fulfilled because available data are frequently poorly used. Meta-analysis has emerged as an important tool for combining clinical evidence. Several examples are presented that compared the results of cumulative meta-analysis of randomized control trials with clinical expert recommendations. These comparisons demonstrated that clinical expert recommendations are often not synchronized with accumulating evidence, and this lack of recognition often resulted in delays in the acceptance of effective drugs and the slow abandonment of possibly harmful therapeutic practices. The problems of inappropriate therapeutic drug use will only intensify as new drugs are introduced and new uses for established drugs are proposed. The rational use of therapeutic drugs can be achieved only through the routine use of meta-analysis on high-quality clinical data. Some suggestions are made to improve the quality of the original research and the ways of assembling meta-analyses and disseminating their results.

Diffusion of Innovation↗

Neurolytic celiac plexus block for treatment of cancer pain: a meta-analysis.

We performed a meta-analysis of the efficacy and safety of neurolytic celiac plexus block (NCPB) for cancer pain. A literature search yielded 59 papers, but data on NCPB in two or more patients was available in only 24 papers. Twenty-one studies were retrospective, one was prospective, and two were randomized and controlled. Cancer type was stated in 1117 of 1145 patients reported (63% pancreatic, 37% nonpancreatic). A bilateral posterior approach with 15-50 mL [corrected] of 50%-100% alcohol was the most common technique. Nonradiologically guided NCPB was performed in 246 patients (32%); guidance was by computed tomography (CT) in 214 (28%), radiograph in 271 (34%), fluoroscopy in 36 (5%), or ultrasound in 7 (< 1%). Good to excellent pain relief was reported in 878/989 patients (89%) during the first 2 wk after NCPB. Long-term followup beyond 3 mo revealed persistent benefit. Partial to complete pain relief continued in approximately 90% of patients alive at 3 mo post-NCPB and in 70%-90% until death even if beyond 3 mo post-NCPB. Patients with pancreatic cancer responded similarly to those with other intraabdominal malignancies. Common adverse effects were transient, including local pain (96%), diarrhea (44%), and hypotension (38%); complications occurred in 2%. This analysis suggests that: 1) NCPB has long-lasting benefit for 70%-90% of patients with pancreatic and other intraabdominal cancers, regardless of the technique used; 2) adverse effects are common but transient and mild; and 3) severe adverse effects are uncommon.

Celiac Plexus↗

Meta-analysis of randomized controlled trials of cranial electrostimulation. Efficacy in treating selected psychological and physiological conditions.

To clarify the diverse published results of cranial electrostimulation (CES) efficacy, we conducted an extensive literature review that identified 18 of the most carefully conducted randomized controlled trials of CES versus sham treatment. For the 14 trials that had sufficient data, we used the techniques of meta-analysis to pool the published results of treating each of four conditions: anxiety (eight trials), brain dysfunction (two trials), headache (two trials), and insomnia (two trials). Because studies utilized different outcome measures, we used an effect size method to normalize measures which we then pooled across studies within each condition. The meta-analysis of anxiety showed CES to be significantly more effective than sham treatment (p < .05). Pooling did not affect results that were individually positive (headache and pain under anesthesia) or negative (brain dysfunction and insomnia). Most studies failed to report all data necessary for meta-analysis. Moreover, in all but two trials, the therapist was not blinded and knew which patients were receiving CES or sham treatment. We strongly recommend that future trials of CES report complete data and incorporate therapist blinding to avoid possible bias.

Anxiety Disorders↗

A survey of current problems in meta-analysis. Discussion from the Agency for Health Care Policy and Research inter-PORT Work Group on Literature Review/Meta-Analysis.

The United States Agency for Health Care Policy and Research brought together representatives from each of the Patient Outcomes Research Teams (PORTs) as the Inter-PORT Meta-Analysis Work Group. The purpose of the meeting was to discuss a wide range of problems the panel had encountered in the area of meta-analysis. Several actual problems were presented, and tentative solutions to those problems were given. The PORTs had to consider issues such as quality assessment, survival analysis, rare events, sensitivity and specificity, and random effects models. The solutions presented represent the methods used by several researchers who are active in the area of meta-analysis.

Evaluation Studies as Topic↗

Ten-year results of the randomized control trials of coronary artery bypass graft surgery: tabular data compiled by the collaborative effort of the original trial investigators. Part 2 of 2.

This metaanalysis has some important general implications for conducting studies to evaluate other treatments as well as for patient management. To avoid missing clinically important differences (eg, 15-20% differences in mortality at 5 years) between the methods of revascularization, study populations should be several times larger than those in our metaanalysis, should include a high proportion of the types of patients for whom surgery is known to be superior to medical therapy, and should be complemented by a systematic overview. We recommend that researchers running large randomized trials consider prospective collaboration with researchers from other trials with a common protocol.

Adult↗

Ten-year results of the randomized control trials of coronary artery bypass graft surgery: tabular data compiled by the collaborative effort of the original trial investigators. Part 1 of 2.

OBJECTIVE: To make available 10-year mortality data compiled and analyzed on patients with stable coronary heart disease (angina not severe enough to necessitate surgery) from all studies in which patients were randomized to initial coronary artery bypass graft (CABG) surgery or initial medical treatment and to determine whether the effects are influenced by the extent of coronary artery disease and degree of left-ventricular function. Data and analyses are presented in tabular form; text is published simultaneously in Lancet. METHODS: We collected individual patient data using standardized forms and, whenever possible, uniform definitions. We used Mantel-Haentel methods to combine data. Restricted means analyses were applied to quantify the extension in survival, and logistic regression analyses were applied to assess whether any baseline covariate affected the treatment differences. RESULTS: Of 2,649 patients, 1,324 were assigned to receive CABG surgery and 1,325 to the medical group. Mean age was 50.8 years; 98.8% were men. 93.7% of the CABG group underwent surgery. 25% of the medical group had undergone surgery at 5 years, 33% at 7 years, and 41% at 10 years. Initial CABG surgery reduced mortality significantly at 5 years (10.2% vs 15.8%; OR = 0.61; P < 0.001), 7 years (15.8% vs 21.7%; OR = 0.68; P < 0.001), and 10 years (26.4% vs 30.5%; OR = 0.83; P < 0.03). Risk reductions were most pronounced in patients with left-main disease compared to those with 3- or 1-2-vessel disease (at 5 years OR = 0.32, 0.58, and 0.77, respectively). CONCLUSIONS: Initial CABG surgery compared to initial medical management reduces mortality, especially in high- and medium-risk patients.

Adult↗

Drug treatment of hypertension in the elderly: a meta-analysis.

PURPOSE: A meta-analysis of the effect of antihypertensive drug treatment on mortality and morbidity in elderly patients. DATA SOURCES: A literature search of published articles from January 1980 to February 1992. STUDY SELECTION: Randomized controlled trials of drug treatment of hypertension with end points for elderly patients reported separately. DATA EXTRACTION: Mortality or morbidity end points or both in patients older than 59 years were pooled by determination of typical odds ratio. A meta-regression was used to study heterogeneity. RESULTS: Nine major trials with 15,559 patients older than 59 years were identified. Death rates in the control group varied between 2.7% and 77.2%; stroke and coronary mortality increased with the severity-of-illness rank (P < 0.001). Overall, treated patients had an approximately 12% reduction in all-cause mortality (odds ratio, 0.88; 95% CI, 0.80 to 0.97; 953 events compared with 1069 events, P = 0.009). There was a 36% reduction in stroke mortality (odds ratio, 0.64; CI, 0.49 to 0.82; 94 events compared with 149 events, P < 0.001) and a 25% reduction in coronary heart disease mortality (odds ratio, 0.75; CI, 0.64 to 0.88; 263 events compared with 350 events, P < 0.001). Coronary morbidity was reduced 15% (odds ratio, 0.85; CI, 0.73 to 0.99; 325 events compared with 379 events, P = 0.036), and stroke morbidity was reduced 35% (odds ratio, 0.65; CI, 0.55 to 0.76; 247 events compared with 382 events, P < 0.001). CONCLUSION: Overall, treatment of hypertension in elderly patients produces a significant benefit in total mortality and cardiovascular morbidity and mortality. However, this benefit may be reduced in the oldest age groups.

Aged↗

Evaluating the quality of articles published in journal supplements compared with the quality of those published in the parent journal.

OBJECTIVES: To determine the relationship between the quality of articles and whether they were published in a supplement or in the parent journal. DATA SOURCES AND STUDY SELECTION: All randomized control trials of drug therapies in adults published in the American Journal of Cardiology, the American Journal of Medicine and the American Heart Journal from January 1990 and obtained in November 1992 by means of a MEDLINE search. A total of 318 abstracts appeared to meet our inclusion criteria, and these articles were obtained and reviewed in further detail. An additional 76 were excluded. DATA EXTRACTION: Three reviewers who were "blinded" and thus unaware of supplement status independently assessed the quality of each of the remaining 242 articles according to a standard quality scoring system. DATA SYNTHESIS: Overall, 67 (27.7%) of the articles were published in journal supplements. Article quality scores ranged from 4.2% to 87.5%, with a mean (+/- SD) score of 37.2% +/- 13.1%. Quality scores were lower in articles published in journal supplements than in those published in the parent journal (t[240] = 2.61, P = .01). The mean quality score for articles published in journal supplements was 33.6% +/- 12.8% compared with a score of 38.5% +/- 13.1% for articles published in the parent journal. Supplement articles included in their final analysis a smaller proportion of the patients initially randomized (t[75] = 2.8, P = .007). CONCLUSION: Our findings suggest that randomized control trials published in journal supplements are generally of inferior quality compared with articles published in the parent journal. The review process surrounding the publication of journal supplements should be consistent with that of the parent journal.

Peer Review, Research↗

Guidelines for meta-analyses evaluating diagnostic tests.

OBJECTIVES: To introduce guidelines for the conduct, reporting, and critical appraisal of meta-analyses evaluating diagnostic tests and to apply these guidelines to recently published meta-analyses of diagnostic tests. DATA SOURCES: Based on current concepts of how to assess diagnostic tests and conduct meta-analyses. They are applied to all meta-analyses evaluating diagnostic tests published in English-language journals from January 1990 through December 1991, identified through MEDLINE searching and by experts in the field. STUDY SELECTION: Meta-analyses were included if at least two of three independent readers regarded their main purpose as the evaluation of diagnostic tests against a concurrent reference standard. DATA EXTRACTION: By three independent readers on the extent to which meta-analyses fulfilled each guideline, with consensus defined as agreement by at least two readers. DATA SYNTHESIS: The guidelines are concerned with determining the objective of the meta-analysis, identifying the relevant literature and extracting the data, estimating diagnostic accuracy, and identifying the extent to which variability is explained by study design characteristics and characteristics of the patients and diagnostic test. In general, the guidelines were only partially fulfilled. CONCLUSION: Meta-analysis is potentially important in the assessment of diagnostic tests. Those reading meta-analyses evaluating diagnostic tests should critically appraise them; those doing meta-analyses should apply recently developed methods. The conduct and reporting of primary studies on which meta-analyses are based require improvement.

Bias↗

A study of manufacturer-supported trials of nonsteroidal anti-inflammatory drugs in the treatment of arthritis.

BACKGROUND: To study the relation between reported drug performance in published trials and support of the trials by the manufacturer of the drug under evaluation, we studied a sample of trials of nonsteroidal anti-inflammatory drugs (NSAIDs) used in the treatment of arthritis. METHODS: All randomized control trials of NSAIDs published between September 1987 and May 1990 identified by MEDLINE were reviewed. If an article met the following criteria (n = 61), it was selected: trials involving adult patients with osteoarthritis or rheumatoid arthritis (n = 180), use of nonsalicylate NSAIDs marketed in the United States (n = 101), randomized control trial (n = 81), duration of the trial 4 or more days (n = 78), and use of an efficacy outcome measure (n = 61). Reviewers, "blinded" to manufacturer status, evaluated the narrative interpretation of results and extracted numeric data on efficacy and toxicity. Manufacturer-associated trials were defined as those that acknowledged an association with a pharmaceutical manufacturer. Because of the scarcity of non-manufacturer-associated trials (n = 9), we report only on the manufacturer-associated articles. RESULTS: Fifty-two publications (85.2%) representing 56 trials were associated with a manufacturer. The manufacturer-associated drug was reported as comparable with (71.4%) or superior to (28.6%) the comparison drug in all 56 trials. These narrative claims of superiority were usually justified with trial data. Of the trials identifying one drug as less toxic (n = 22), the manufacturer-associated drug's safety was reported as superior to the comparison drug in 86.4% of cases. Justification for the narrative interpretation of the trial findings regarding less toxicity was provided in only 12 (54.5%) of 22 trials. CONCLUSION: The manufacturer-associated NSAID is almost always reported as being equal or superior in efficacy and toxicity to the comparison drug. These claims of superiority, especially in regard to side effect profiles, are often not supported by trial data. These data raise concerns about selective publication or biased interpretation of results in manufacturer-associated trials.

Anti-Inflammatory Agents, Non-Steroidal↗

Residential proximity to electricity transmission and distribution equipment and risk of childhood leukemia, childhood lymphoma, and childhood nervous system tumors: systematic review, evaluation, and meta-analysis.

In 1979, Wertheimer and Leeper reported an increased risk of cancer mortality among children living near 'electrical wiring configurations' suggestive of high current flow. Since then, numerous, often inconclusively small, investigations with conflicting results have studied the possible association between exposure to electric and magnetic fields (EMF) and health effects. The high prevalence of exposure to EMF has drawn attention to the issue of carcinogenesis. We report here the results of a meta-analysis of 13 epidemiologic studies of residential proximity to electricity transmission and distribution equipment and risk of childhood leukemia, lymphoma, and nervous system tumors. The combined relative risks for leukemia, lymphoma, and nervous system tumors are 1.49 (95 percent confidence interval [CI] = 1.11-2.00); 1.58 (CI = 0.91-2.76); and 1.89 (CI = 1.34-2.67) respectively. The reports of the primary studies were evaluated for epidemiologic quality and adequacy of exposure assessment. We found no statistically significant relation between combined relative risk estimates and 15 indicators of epidemiologic quality. Assessment of EMF exposure in the primary studies was found to be imperfect and imprecise. Additional high quality epidemiologic research, incorporating comprehensive assessments of EMF exposure collected concurrently with surrogate measures of exposure, is needed to confirm these results.

Adolescent↗

Antipsychotic drugs: is more worse? A meta-analysis of the published randomized control trials.

Effectiveness and side-effects of high- versus low-dose neuroleptic treatment of chronic psychosis have been assessed through a meta-analysis of 22 published randomized control trials comparing different neuroleptic doses. No incremental clinical improvement was found at doses above 375 mg equivalent of chlorpromazine, while a significant increase in adverse reactions was observed.

Antipsychotic Agents↗

Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain: a meta-analysis.

PURPOSE: To assess the efficacy and safety of nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of cancer pain by meta-analyses of the published randomized control trials (RCTs). PATIENTS AND METHODS: Twenty-five studies met inclusion criteria for analysis. Of these, 13 tested a single-dose effect, nine multiple-dose effects, and three both single- and multiple-dose effects of 16 different NSAIDs in a total of 1,545 patients. Baseline pain intensity (when provided) of moderate or higher was indicated in 81% of patients. RESULTS: Single-dose NSAID studies found greater analgesic efficacy than placebo, with rough equivalence to 5 to 10 mg of intramuscular morphine. Pain scores differed insignificantly for aspirin versus three other NSAIDs. Analgesic responses to low- and high-dose NSAIDs suggested a dose-response relationship, but this was not statistically significant. Recommended and supramaximal single doses of three NSAIDs produced comparable changes in pain scores, which indicates a ceiling analgesic effect. Common side effects included upper gastrointestinal symptoms, dizziness, and drowsiness. The incidence of side effects showed a trend to increase with dose, without a ceiling effect, and to increase with multiple doses. Single or multiple doses of weak opioids (WO) alone or in combination (WO/C) with nonopioid analgesics did not produce greater analgesia than NSAIDs alone. Single doses of WO/C analgesics produced more side effects than NSAIDs alone, although both side effect incidence and patient dropout rates were equal when multiple doses were administered. CONCLUSION: These findings question whether the traditional World Health Organization (WHO) second analgesic step (addition of a weak opioid when pain is inadequately treated by a nonopioid analgesic alone) is warranted. A lack of comparable studies precluded testing the hypothesis that NSAIDs are particularly effective for malignant bone pain.

Anti-Inflammatory Agents, Non-Steroidal↗

A meta-analysis of randomized placebo control trials in Fontaine stages III and IV peripheral occlusive arterial disease.

In patients with Fontaine Stage III and IV POAD unsuitable for arterial reconstruction, Iloprost, a prostacyclin analogue, has been shown in six RCTs to have a significant (p < 0.05) beneficial effect with regards to the probability of being alive with both legs at six months follow-up. Iloprost has significant (p < 0.05) beneficial effects over placebo on ulcer healing and pain relief, but these were relatively soft endpoints to study when side effects may have unblinded many observers and patients. Further studies are indicated to investigate the possible benefit of repeated courses of treatment with Iloprost in patients with non-reconstructable Fontaine Stage III and IV POAD as well as studies looking at patients who may be suitable only for relatively high risk reconstructions. Meta-analysis of all other RCTs of pharmacotherapeutic agents in patients with Fontaine Stage III and IV POAD showed no significant benefit over placebo for any of the endpoints reported.

Alprostadil↗

Examination of the early 'learning curve' for transcatheter closure of patent ductus arteriosus using the Rashkind occluder. PDA Closure Comparative Study Group.

BACKGROUND: Results of transcatheter implantation of the Rashkind double umbrella occluder for treatment of patent ductus arteriosus (PDA) have improved over time. We evaluated factors associated with changes in outcomes seen in the early clinical experience with this device. METHODS AND RESULTS: We reviewed records of otherwise healthy pediatric patients undergoing occluder implantation for isolated PDA between 1982 and 1987 at six major US and Canadian referral centers. Logistic regression was used to assess the impact of ductal size, patient age and weight, calendar time, prior intrainstitutional occluder experience, and residual center effects on closure rates. There were no study deaths. Of 180 occluder placement attempts, 76.7% (95% confidence limits = 70.5%, 83.0%) produced PDA closure by auscultation at 14-month cardiology follow-up or its equivalent. Success probabilities increased in a linear fashion as ductus size decreased, ranging from 41.7% for large (4.1 to 9.0-mm) ducts to 89.4% for small (1.5 to 2.5-mm) lesions. PDA occluder closure rates also improved over time, increasing from 47.4% in 1982-1983 to 84.6% in 1986 and 83.1% in 1987. Multivariate logistic regression indicated that improved outcomes were mainly attributable to decrease in the size of treated ducts over time. Independent of this patient selection, improvements in outcome were less strongly associated with cumulative intracenter experience, calendar time, and age. CONCLUSIONS: Increasing closure rates seen over time primarily reflected more judicious selection of patients as experience accumulated. However, other factors also contributed to the observed trends. An analysis of current treatment results would be of considerable interest.

Age Factors↗