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Biomedical subjects

Otavio Clark

Publications and source records attributed to Otavio Clark.

6 recordsLinked to original sources
PubMed2005

Use of re-randomized data in meta-analysis.

BACKGROUND: Outcomes collected in randomized clinical trials are observations of random variables that should be independent and identically distributed. However, in some trials, the patients are randomized more than once thus violating both of these assumptions. The probability of an event is not always the same when a patient is re-randomized; there is probably a non-zero covariance coming from observations on the same patient. This is of particular importance to the meta-analysts. METHODS: We developed a method to estimate the relative error in the risk differences with and without re-randomization of the patients. The relative error can be estimated by an expression depending on the percentage of the patients who were re-randomized, multipliers (how many times more likely it is to repeat an event) for the probability of reoccurrences, and the ratio of the total events reported and the initial number of patients entering the trial. RESULTS: We illustrate our methods using two randomized trials testing growth factors in febrile neutropenia. We showed that under some circumstances the relative error of taking into account re-randomized patients was sufficiently small to allow using the results in the meta-analysis. Our findings indicate that if the study in question is of similar size to other studies included in the meta-analysis, the error introduced by re-randomization will only minimally affect meta-analytic summary point estimate. We also show that in our model the risk ratio remains constant during the re-randomization, and therefore, if a meta-analyst is concerned about the effect of re-randomization on the meta-analysis, one way to sidestep the issue and still obtain reliable results is to use risk ratio as the measure of interest. CONCLUSION: Our method should be helpful in the understanding of the results of clinical trials and particularly helpful to the meta-analysts to assess if re-randomized patient data can be used in their analyses.

Colony-Stimulating Factors↗
PubMed2004

Immunocytochemical detection of epithelial cells in the bone marrow of primary breast cancer patients: a meta-analysis.

PURPOSE: The immunocytochemical detection of epithelial cells in the bone marrow (BM) of breast cancer (BC) patients has been shown to have prognostic importance in several studies. We conducted a systematic review of the literature and a meta-analysis to assess the specificity, rate of positivity and correlation with known prognostic variables as well as with disease free (DFS) and overall survival (OS). DESIGN: We performed a systematic review from the published literature. We included studies with at least 20 previously untreated BC patients as well as non-BC controls that evaluated the presence of epithelial cells in BM using immunocytochemistry (IC). RESULTS: We identified 14 eligible studies with 3253 BC patients and 532 controls. Our results showed that IC has an overall rate of positivity of 31% (95% CI: 30-33%), and specificity of 96% (compared to normal patients) (95% CI: 0.94-0.98). We observed significant direct correlations between IC BM positivity and the primary tumor's presence with expression of estrogen receptors, larger size and higher histologic grade as well as with the presence of more than 3 positive axillary lymph nodes. At 5 years of follow up IC positivity correlated directly with a lower DFS (relative risk=1.60; 95% CI: 1.39-1.83) and OS (relative risk=1.73; 95% CI: 1.29-2.31). The prognostic impact of BM positivity seemed to decrease with time. CONCLUSIONS: We conclude that the finding of epithelial cells in BM of BC patients correlates with several known prognostic factors and has adverse impact in the DFS and OS of these patients that seems, however, to decrease with time.

Bone Marrow↗
PubMed2003

Pharmaceutical industry sponsorship and research outcome and quality: systematic review.

OBJECTIVE: To investigate whether funding of drug studies by the pharmaceutical industry is associated with outcomes that are favourable to the funder and whether the methods of trials funded by pharmaceutical companies differ from the methods in trials with other sources of support. METHODS: Medline (January 1966 to December 2002) and Embase (January 1980 to December 2002) searches were supplemented with material identified in the references and in the authors' personal files. Data were independently abstracted by three of the authors and disagreements were resolved by consensus. RESULTS: 30 studies were included. Research funded by drug companies was less likely to be published than research funded by other sources. Studies sponsored by pharmaceutical companies were more likely to have outcomes favouring the sponsor than were studies with other sponsors (odds ratio 4.05; 95% confidence interval 2.98 to 5.51; 18 comparisons). None of the 13 studies that analysed methods reported that studies funded by industry was of poorer quality. CONCLUSION: Systematic bias favours products which are made by the company funding the research. Explanations include the selection of an inappropriate comparator to the product being investigated and publication bias.

Clinical Trials as Topic↗
PubMed2002

Erythropoietin, uncertainty principle and cancer related anaemia.

BACKGROUND: This study was designed to evaluate if erythropoietin (EPO) is effective in the treatment of cancer related anemia, and if its effect remains unchanged when data are analyzed according to various clinical and methodological characteristics of the studies. We also wanted to demonstrate that cumulative meta-analysis (CMA) can be used to resolve uncertainty regarding clinical questions. METHODS: Systematic Review (SR) of the published literature on the role of EPO in cancer-related anemia. A cumulative meta-analysis (CMA) using a conservative approach was performed to determine the point in time when uncertainty about the effect of EPO on transfusion-related outcomes could be considered resolved. PARTICIPANTS: Patients included in randomized studies that compared EPO versus no therapy or placebo. MAIN OUTCOME MEASURES: Number of patients requiring transfusions. RESULTS: Nineteen trials were included. The pooled results indicated a significant effect of EPO in reducing the number of patients requiring transfusions [odds ratio (OR) = 0.41; 95%CI: 0.33 to 0.5; p < 0.00001;relative risk (RR) = 0.61; 95% CI: 0.54 to 0.68]. The results remain unchanged after the sensitivity analyses were performed according to the various clinical and methodological characteristics of the studies. The heterogeneity was less pronounced when OR was used instead of RR as the measure of the summary point estimate. Analysis according to OR was not heterogeneous, but the pooled RR was highly heterogeneous. A stepwise metaregression analysis did point to the possibility that treatment effect could have been exaggerated by inadequacy in allocation concealment and that larger treatment effects are seen at hb level > 11.5 g/dl. We identified 1995 as the point in time when a statistically significant effect of EPO was demonstrated and after which we considered that uncertainty about EPO efficacy was resolved. CONCLUSION: EPO is effective in the treatment of anemia in cancer patients. This could have already been known in 1995 if a CMA had been performed at that time.

Anemia↗
PubMed2002

Quality and methods of developing practice guidelines.

BACKGROUND: It is not known whether there are differences in the quality and recommendations between evidence-based (EB) and consensus-based (CB) guidelines. We used breast cancer guidelines as a case study to assess for these differences. METHODS: Five different instruments to evaluate the quality of guidelines were identified by a literature search. We also searched MEDLINE and the Internet to locate 8 breast cancer guidelines. These guidelines were classified in three categories: evidence based, consensus based and consensus based with no explicit consideration of evidence (CB-EB). Each guideline was evaluated by three of the authors using each of the instruments. For each guideline we assessed the agreement among 14 decision points which were selected from the NCCN (National Cancer Comprehensive Network) guidelines algorithm. For each decision point we recorded the level of the quality of the information used to support it. A regression analysis was performed to assess if the percentage of high quality evidence used in the guidelines development was related to the overall quality of the guidelines. RESULTS: Three guidelines were classified as EB, three as CB-EB and two as CB. The EB guidelines scored better than CB, with the CB-EB scoring in the middle among all instruments for guidelines quality assessment. No major disagreement in recommendations was detected among the guidelines regardless of the method used for development, but the EB guidelines had a better agreement with the benchmark guideline for any decision point. When the source of evidence used to support decision were of high quality, we found a higher level of full agreement among the guidelines' recommendations. Up to 94% of variation in the quality score among guidelines could be explained by the quality of evidence used for guidelines development. CONCLUSION: EB guidelines have a better quality than CB guidelines and CB-EB guidelines. Explicit use of high quality evidence can lead to a better agreement among recommendations. However, no major disagreement among guidelines was noted regardless of the method for their development.

Algorithms↗