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PubMed2005

Early stopping of clinical trials.

Early stopping of clinical trials in favour of a new treatment creates ethical and scientific difficulties, which are different from those associated with early stopping due to toxicity or futility. Two major breast cancer trials have recently taken such a decision, and the problem is relevant for several ongoing trials. Here we argue that such a decision should be taken with the utmost gravity and should be based on a clear overall clinical benefit for the new treatment, and not as an automatic response to crossing a predefined threshold. Predefined rules can be used to trigger a debate within the Independent Data Monitoring and Safety Committee (IDMC) about early stopping, but the IDMC should retain the responsibility of assessing overall clinical benefit in making its recommendation.

Breast Neoplasms↗
PubMedDate not supplied

Practical aspects in data monitoring: a brief review.

Monitoring interim accumulating data in a clinical trial for evidence of therapeutic benefit or toxicity is a frequent policy, usually carried out by an independent scientific committee. Repeated testing at conventional critical values can substantially inflate the type I error rate. To maintain acceptable levels, group sequential and stochastic curtailment have been developed for clinical trials. One should not view such methods as absolute rules, but as useful guides. The decision process to terminate a trial early is complex and necessitates an accounting for many factors. The Beta-Blocker Heart Attack Trial provides an excellent example of many of these issues.

Clinical Trials as Topic↗
PubMedDate not supplied

Operational design and quality control in the CATCH multicenter Trial.

BACKGROUND: The Child and Adolescent Trial for Cardiovascular Health (CATCH) was the first multicenter school-based research study to employ the fundamentals of clinical trials including the standardized protocol and Manuals of Operation, a steering committee for study governance, a distributed data system, an extensive quality control system, and a Data and Safety Monitoring Board. METHOD: CATCH tested the effectiveness of changes in school lunches, physical education, smoking policy, curricula, and family activities. Ninety-six elementary schools in four states were randomized to intervention or control conditions. The baseline cohort comprised 5, 106 ethnically diverse third graders followed through fifth grade. RESULTS: The percentages of calories from fat and saturated fat were reduced significantly more in the intervention school lunches than among the controls. Significant increases in moderate to vigorous activity levels in existing physical education classes were made as well. Changes in self-reported dietary, physical activity, and psychosocial measures were significant. There were no significant differences in the physiological measures. Measurement error was generally low for all physiologic measures except skinfolds, indicating a high level of reliability. Across all sites, the coefficients of variation for lipids, height, and weight were less than 3%, whereas for skinfolds, they were considerably higher, ranging from 6 to 8%. Intraclass correlations for lipid studies were also uniformly high at 0.99. Interobserver agreement scores for SOFIT were greater than 90% for 9 of the 11 activities observed. Data entry error rates were low with less than five errors per 1,000 fields for all forms. CONCLUSIONS: The CATCH results provided more scientific evidence on the importance of schools in the population approach to health promotion. Many of the strategies used in this complex multicenter trial in the areas of design and analysis, measurement, training, data management, and quality control protocols might be appropriate for adoption in other studies.

Adolescent↗
PubMed1987

Program on Surgical Control of the Hyperlipidemias (POSCH): recruitment experience.

The Program on Surgical Control of the Hyperlipidemias (POSCH) is an investigator-initiated NHLBI grant-funded secondary coronary heart disease intervention trial using partial ileal bypass (PIB) for lipid reduction. Randomization started in September 1975 and ended in July 1983 with enrollment of 838 participants (421 surgery, 417 controls). The trial is scheduled to reveal the atherosclerosis impact of the lipid changes in 1990, at which time the average individual in the program will have been followed for 9.6 years. Initially, the magnitude of the recruitment task was greatly underestimated. An area containing 500,000 people was judged to be sufficient to randomize one patient per month. Actually, a population of 2.4-10.5 million, depending upon proximity to a clinic, was needed to achieve this goal. The study design was changed in 1981, due to recruitment costs, with reduction of the number of individuals to be randomized from 1000 to 838 and with extension of the duration of minimum follow-up from 5 to 7 years. Only with the development of a uniform model clinic concept, with specified levels of performance calculated from actual recruitment data, did accrual of patients into the trial become predictable and achievable. Some of the recruitment delays in POSCH were related to problems, in part generic to the existent grant funding mechanism and associated with decisions made by NHLBI and its Advisory Council. These delays were manifested by denial of reallocation of approved funds to initiate replacement clinics for discontinued ones, an 18-month delay in implementation of a protocol change in lipid criteria suggested by the Data Monitoring Committee, and a 2-year delay in the starting date for the fourth active clinic.

Adult↗
PubMed2005

Hyperbaric oxygen for carbon monoxide poisoning : a systematic review and critical analysis of the evidence.

Poisoning with carbon monoxide (CO) is an important cause of unintentional and intentional injury worldwide. Hyperbaric oxygen (HBO) enhances CO elimination and has been postulated to reduce the incidence of neurological sequelae. These observations have led some clinicians to use HBO for selected patients with CO poisoning, although there is considerable variability in clinical practice. This article assesses the effectiveness of HBO compared with normobaric oxygen (NBO) for the prevention of neurological sequelae in patients with acute CO poisoning. The following databases were searched: MEDLINE (1966 to present), EMBASE (1980 to present), and the Controlled Trials Register of the Cochrane Collaboration, supplemented by a manual review of bibliographies of identified articles and discussion with recognised content experts. All randomised controlled trials involving people acutely poisoned with CO, regardless of severity, were examined. The primary analysis included all trials from which data could be extracted. Sensitivity analysis examined trials with better validity (defined using the validated instrument of Jadad) and those enrolling more severely poisoned patients. Two reviewers independently extracted from each trial, including information on the number of randomised patients, types of participants, the dose and duration of the intervention, and the prevalence of neurological sequelae at follow-up. A pooled odds ratio (OR) for the presence of neurological symptoms at 1-month follow-up was calculated using a random effects model. Bayesian models were also investigated to illustrate the degree of certainty about clinical effectiveness. Eight randomised controlled trials were identified. Two had no evaluable data and were excluded. The remaining trials were of varying quality and two have been published only as abstracts. The severity of CO poisoning varied among trials. At 1-month follow-up after treatment, sequelae possibly related to CO poisoning were present in 242 of 761 patients (36.1%) treated with NBO, compared with 259 of 718 patients (31.8%) treated with HBO. Restricting the analysis to the trials with the highest quality scores or those that enrolled all patients regardless of severity did not change the lack of statistical significance in the outcome of the pooled analysis. We found empiric evidence of multiple biases that operated to inflate the benefit of HBO in two positive trials. In contrast, the interpretation of negative trials was hampered by low rates of follow-up, unusual interventions for control patients and inclusion of less severely poisoned patients. Collectively, these limitations may have led negative trials to overlook a real and substantial benefit of HBO (type II error). There is conflicting evidence regarding the efficacy of HBO treatment for patients with CO poisoning. Methodological shortcomings are evident in all published trials, with empiric evidence of bias in some, particularly those that suggest a benefit of HBO. Bayesian analysis further illustrates the uncertainty about a meaningful clinical benefit. Consequently, firm guidelines regarding the use of HBO for patients with CO poisoning cannot be established. Further research is needed to better define the role of HBO, if any, in the treatment of CO poisoning. Such research should not exclude patients with severe poisoning, have a primary outcome that is clinically meaningful and have oversight from an independent data monitoring and ethics committee.

Carbon Monoxide Poisoning↗
PubMed2005

Management of the relapsed/refractory myeloma patient: strategies incorporating lenalidomide.

The immunomodulatory drug (IMiD) lenalidomide is a more potent immunomodulator than thalidomide with respect to its effects on cytokine modulation and increased T-cell proliferation. Of all the IMiDs, clinical trial data are most mature for lenalidomide. In phase I studies, dose-limiting toxicities of lenalidomide were limited to myelosuppression and a response rate of 72% was seen in relapsed/refractory patients. Three phase II studies subsequently evaluated the efficacy of single-agent lenalidomide or lenalidomide in combination with dexamethasone. As a single agent for post-transplant salvage therapy, lenalidomide 25 mg every 3 weeks has shown response rates as high as 44%. For patients with relapsed/refractory multiple myeloma, the MM-007 study has shown that lenalidomide alone or in combination with dexamethasone provides response rates between 37% and 41%. In MM-007, median progression-free survival was 5.5 months at early analysis and the median overall survival has yet to be reached. Preliminary data for the single-arm, multicenter, open-label MM-014 study showed that median time to progression was 5.6 months. Response rates indicate that 70% of patients had stable disease or better as the best response to treatment. Two randomized, phase III trials (MM-009 and MM-010) evaluated lenalidomide with high-dose dexamethasone versus high-dose dexamethasone alone for the treatment of relapsed/refractory multiple myeloma. Both MM-009 and MM-010 provided remarkably similar response rates for patients receiving lenalidomide and dexamethasone. In both trials response rates with the combination were greater than twice the response rates seen with high-dose dexamethasone alone. Indeed, an independent Data Monitoring Committee determined that both trials exceeded the prespecified efficacy value of P<.0015, recommending that the trials be discontinued and that lenalidomide be offered to patients on the dexamethasone arm of the trial if clinically indicated. Toxicities observed in studies of lenalidomide alone were low; the incidence of peripheral neuropathy was significantly lower than those noted in trials using thalidomide. Thrombocytopenia was a significant grade 3 or 4 toxicity observed; however, it was manageable with dose reduction. In contrast with high-dose dexamethasone, deep vein thrombosis has emerged as an important toxicity. Lenalidomide is currently being tested in combination with both standard and novel agents, including bortezomib, for patients with relapsed/refractory multiple myeloma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

[Clinical trials on medical products for human use in the case of acutely incapacitated patients within the fields of neurology and neurosurgery; implications of the new European legislation].

To comply with the European directive on clinical trials on medical products for human use, an amendment to the Dutch Medical Research Involving Human Beings Act was formally submitted in the Netherlands on the 27th February 2003. The objective is harmonisation of legislation and the protection of patients participating in clinical trials within the European Union. An important element of the directive is additional protection for incapacitated patients. In the fields of neurology and neurosurgery much research, mainly phase III, is conducted into the safety and efficacy of pharmaceutical products in emergency situations such as traumatic skull-brain injury or an acute cerebral infarct. Future emergency research in patients with acute cerebral disorders will be hindered by the (shortly legal) requirement that prior proxy consent is mandatory and the fact that individual patients must directly benefit as a result of their participation. This unintended negative effect may be considered contrary to the ethical principals for conducting good scientific research to improve treatment results. Also, it may lead to a scientific backlog compared to countries outside of the European Union. In the case of emergency phase-III research among acutely incapacitated patients we recommend that the Central Committee on Research Involving Human Subjects [Dutch acronym: CCMO] tests the research, that trials have an independent committee to monitor the data and safety, that an independent physician may grant consent for the patient to participate and that the consent of the patient's representative(s) is obtained within 24 hours of the patient being included in the trial.

Clinical Trials, Phase III as Topic↗
PubMed1994

On the development of the Medical Research Council trial of alpha-interferon in metastatic renal carcinoma. Urological Working Party Renal Carcinoma Subgroup.

This paper describes the steps taken by the British Medical Research Council (MRC) in developing the MRC RE01 trial, a randomized clinical trial for patients with metastatic renal cancer; we discuss the reasons for adopting a triangular sequential design and the impact that this has upon the monitoring of the trial. It had been suggested to the MRC that a trial of biological agents for metastatic renal carcinoma should be initiated. The Cancer Therapy Committee (CTC) of the MRC, through its associated site specific working parties, is responsible for designing and co-ordinating randomized trials of alternative treatments in cancer in solid tumours. Since no MRC working party for renal carcinoma existed at that time, development began by the formation of an ad hoc group set up under the auspices of the CTC. They assessed, by means of a postal questionnaire, U.K. interest in the trials of, and modalities utilized for, treatment of renal cancer. The responses focused attention on the important questions to ask and indicated the level of potential collaboration. These responses and related clinical and statistical issues suggested a protocol to compare medroxy-progesterone acetate (MPA) against alpha-interferon (alpha-IFN). In view of the special problems of comparing an expensive and potentially toxic therapy with an inexpensive and non-toxic standard, a sequential design was used rather than a fixed sample size design. Statistical issues raised and solutions provided are described. The method of establishing the trial data monitoring committee and a brief review of mortality from renal carcinoma in England and Wales are also included. The trial opened to patient recruitment on 1 January 1992. The formal statements regarding statistical issues that appear in the formal trial protocol (RE01) are set out in the Appendix.

Aged↗
PubMed2003

Clinical trials in jeopardy.

BACKGROUND: The controlled clinical trial, the gold standard for clinical research, is in jeopardy. The pharmaceutical industry is rapidly expanding its command over clinical trials but scientific rigor requires independence and objectivity. Safeguarding such criteria is hard because industrial sponsors, benefit directly from favorable results and are virtually in complete control. OBJECTIVE: To review flawed procedures jeopardizing the credibility of trials and to look for possible solutions to the conflict between sponsored industry and scientific independence. RESULTS: Flawed procedures jeopardizing current clinical trials can be listed as follows. Industries, at least in Europe, are allowed to choose their own independent protocol review board prior for approval. The independent protocol review board approves protocols even when the research is beyond the scope of its expertise. Health institutions hosting multicenter trials are requested to refrain from scientific or ethic assessment of the trial. Trial monitors are often employees of industry. Data control is predominantly in the hands of the sponsor. Interim analyses are rarely performed by independent groups. The scientific committee of the trial consists largely of prominent but otherwise uninvolved physicians attached to the study. The analysis and report of the trial is generally provided by clinical associates of the pharmaceutical companies and, after a brief review, co-signed by prominent physicians attached to the study. POSSIBLE SOLUTIONS: Possible solutions to the conflict between sponsored industry and scientific independence could include the following. Surveillance by independent observers during each stage of the trial is desirable. In contrast, tight control of study data, analysis, and interpretation by the commercial sponsor is undesirable. If, instead, the pharmaceutical industry allows the profession to more actively participate in different stages of the trial, scientific research will be better served, reasonable biological questions will be better answered, and, because the profession will be more convinced of the objective character of the research, it will not be counterproductive to the sales.

Conflict of Interest↗
PubMed1991

How should results from completed studies influence ongoing clinical trials? The CAFA Study experience.

Seven randomized studies during the past 5 years have evaluated or are evaluating the efficacy of warfarin or aspirin or both in decreasing the risk of embolic events in patients with nonrheumatic atrial fibrillation. By March 1990, two of the studies had been published, both of which showed a statistically significant decrease in embolic events in patients treated with warfarin and a low rate of major bleeding events. The investigators associated with the other ongoing studies were forced to consider how these results should affect the decision to recruit and continue follow-up of patients in their own studies. The Steering Committee of the Canadian Atrial Fibrillation Anticoagulation (CAFA) study thought the newly published results from other studies were valid, clinically important, and generalizable. The committee considered the following options for the CAFA study: continue patient recruitment as planned, provide the data available in CAFA to its External Safety and Efficacy Monitoring Committee for analysis to determine whether the CAFA data already showed a benefit of warfarin, stop patient recruitment but continue to follow patients in the group to which they were assigned, stop the trial immediately and perform a final analysis, and attempt to perform a meta-analysis of all data available from all trials. The Steering Committee of CAFA decided that the evidence of benefit with warfarin, from the two published studies, was sufficiently compelling as to stop recruitment into CAFA without any preliminary examination of the CAFA data.

Aspirin↗
PubMedDate not supplied

[Pharmacy Department standard procedures for clinical trial development].

INTRODUCTION: Regulations on good clinical practice in the execution of clinical trials require the establishment and compliance of normalised working procedures by the hospital Pharmacy Department. These procedures must indicate precisely each one of the processes involved in their development, e.g. the reception, custody, storage, preparation and dispensing of research samples. OBJECTIVE: The aim of the present study is to analyse the information included in clinical trial protocols involved in the circulation of drug samples during the research stage and, based on the results obtained, to develop normalised working procedures for our hospital Pharmacy Department in order to carry out these clinical trials. MATERIAL AND METHODS: Eleven items were defined in order to describe key processes involved in identification, storage, receipt, preparation, dispensation, administration, maintenance and return of research samples, as well as those related to the beginning and end or closing of a clinical trial. Information included in 39 clinical trial protocols that had been sent to the Hospital Ethics Committee for evaluation between January and August of 2002 and was analysed in terms of the items previously defined. RESULTS: 46% of the protocols included data from the monitor or person representing the sponsor. 64% adequately described conservation and storage conditions of the research samples; but in 39% of the studied cases external labelling descriptions did not comply with legislation. Only 15% of the cases included clear instructions on research sample reception and its acknowledgement. 25.6% reported correct handling and/or preparation instructions for research samples with parenteral administration. Sample dispensation procedures were correctly described in no more than 5.1% of the protocols analyzed. 41% included information for patients, relatives or nurses on administration and handling of research samples, but none of them included specific information pamphlets or three-page leaflets. Procedures for either returning research samples to the sponsor or for their maintenance and replacement were not specified in the 71.8 and 100% of the cases, respectively. Likewise, trial ending or closing dates as well as procedures that must be followed by the Hospital Pharmacy Department during these processes were not stated in 89.7% of the protocols. Finally, only 30.8% of the cases explicitly cite the hospital Pharmacy Department. CONCLUSION: These results support and justify the need to improve clinical trial protocols in order for them to be performed in a secure, effective and efficient way. Besides, they have been the starting point to devise the normalised working procedures of the hospital Pharmacy Department for the development of the clinical trials.

Clinical Protocols↗
PubMed2006

Refining the postmenopausal breast cancer treatment paradigm: the FACE trial.

It is clear that letrozole and anastrozole provide significant benefits for patients with breast cancer. However, possible differences in efficacy have been suggested by varying degrees of aromatase inhibition and effectiveness in the neoadjuvant and first-line settings. Analyses of aromatase inhibitor-treated patient subgroups within the Arimidex, Tamoxifen, Alone or in Combination trial and Breast International Group 1-98 trial, and the National Cancer Institute of Canada Clinical Trials Group's MA.17 study, have also suggested some differences in efficacy. The question is how best to maximize these differences to benefit specific patient subgroups, such as postmenopausal women with node-positive disease. Nodal status is one of the strongest prognostic factors for breast cancer recurrence and several studies have shown that patients with node-positive disease are at higher risk for early relapse. It is thought that patients at increased risk for early relapse may be better treated with an aromatase inhibitor upfront, but the guidelines are unclear as to which aromatase inhibitor should be used. To answer this important question quickly, the Femara Anastrozole Clinical Evaluation (FACE) trial is recruiting node-positive patients and randomizing them to receive either early adjuvant letrozole or early adjuvant anastrozole. The trial has been designed to differentiate between the two drugs in the shortest possible time frame by using patients at increased risk of early recurrence of breast cancer, so that the required number of events to initiate analysis will be obtained more quickly. In total, 4000 patients who have recently undergone surgery for node-positive primary breast cancer (and who have no clinical or radiological evidence of recurrent disease or metastasis) are being enrolled around the world. The FACE trial will not only provide an efficacy evaluation between these two aromatase inhibitors but also provide a valuable head-to-head comparison of the safety profiles of adjuvant letrozole and anastrozole. The data will be transferred to an independent academic organization, the Istituto Nazionale Tumori (Michelangelo Foundation, Milan, Italy), which will verify and analyze the data, removing any perception of bias. An Independent Data Monitoring Committee will then decide when and how the trial data are to be released. The results are expected to further refine the treatment paradigm for breast cancer in postmenopausal patients with node-positive disease.

Anastrozole↗
PubMed1977

Design of a study to evaluate drug therapy of serious ventricular rhythm disturbances after an acute myocardial infarction.

A study was designed to investigate whether long-term use of aprindine can prevent sudden death from primary ventricular fibrillation. Patients with a proven recent myocardial infarction and malignant ventricular arrhythmias occurring late after the acute episode were asked to participate in a 1-yr, double-blind, randomized, placebo-controlled trial to suppress the rhythm disturbances observed on an ambulatory electrocardiogram. Particular care was taken to monitor drug adherence. Arrhythmia detection by ambulatory electrocardiography was used to assess drug efficacy; side-effects establish the maximum tollerated dose for each individual patient. Aprindine was therefore used under optimal circumstances. An interactive computer system served as a data base and provided the investigators and the monitoring committee with all the information required for a proper evaluation of the progress of the study.

Aprindine↗
PubMed1999

American Society of Clinical Oncology technology assessment on breast cancer risk reduction strategies: tamoxifen and raloxifene.

OBJECTIVE: To conduct an evidence-based technology assessment to determine whether tamoxifen and raloxifene as breast cancer risk-reduction strategies are appropriate for broad-based conventional use in clinical practice. POTENTIAL INTERVENTION: Tamoxifen and raloxifene. OUTCOME: Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefits. EVIDENCE: A comprehensive, formal literature review was conducted for tamoxifen and raloxifene on the following topics: breast cancer risk reduction; tamoxifen side effects and toxicity, including endometrial cancer risk; tamoxifen influences on nonmalignant diseases, including coronary heart disease and osteoporosis; and decision making by women at risk for breast cancer. Testimony was collected from invited experts and interested parties. VALUES: More weight was given to publications that described randomized trials. BENEFITS/HARMS/COSTS: The American Society of Clinical Oncology (ASCO) Working Group acknowledges that a woman's decision regarding breast cancer risk-reduction strategies will depend on the importance and weight attributed to the information provided regarding both cancer and non-cancer-related risks. CONCLUSIONS: For women with a defined 5-year projected risk of breast cancer of >/= 1.66%, tamoxifen (at 20 mg/d for up to 5 years) may be offered to reduce their risk. It is premature to recommend raloxifene use to lower the risk of developing breast cancer outside of a clinical trial setting. On the basis of available information, use of raloxifene should currently be reserved for its approved indication to prevent bone loss in postmenopausal women. Conclusions are based on single-agent use of the drugs. At the present time, the effect of using tamoxifen or raloxifene with other medications (such as hormone replacement therapy), or using tamoxifen and raloxifene in combination or sequentially, has not been studied adequately. The continuing use of placebo-controlled trials in other risk-reduction trials highlights the current unanswered issues concerning the use of such interventions, especially when the influence on net health benefit remains to be determined. Breast cancer risk reduction is a rapidly evolving area. This technology assessment represents an ongoing process with existing plans to monitor and review data and to update recommendations in a timely matter. (See VALIDATION: The conclusions of the Working Group were evaluated by the ASCO Health Services Research Committee and by the ASCO Board of Directors. SPONSOR: American Society of Clinical Oncology.

Anticarcinogenic Agents↗
PubMed2003

Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial.

PURPOSE: To determine whether continuing paclitaxel for an extended time period in women with advanced ovarian cancer who had achieved a clinically defined complete response to a platinum/paclitaxel-based chemotherapy could prolong subsequent progression-free survival (PFS) and affect ultimate survival. PATIENTS AND METHODS: Patients were randomly assigned to either three or 12 cycles of single-agent paclitaxel administered every 28 days and were then followed up for progression-free and overall survival. RESULTS: As of September 6, 2001, 277 patients (262 assessable) had entered the trial, with a total of 54 PFS events having developed among 222 patients with follow-up data. With the exception of peripheral neuropathy, there were no major differences in toxicity between the regimens. The median PFS was 21 and 28 months in the three-cycle and 12-cycle paclitaxel arms, respectively. One-sided P values from an unadjusted log-rank test and an adjusted Cox model analysis (for stratification factors) were.0035 and.0023, respectively, both in favor of the 12-cycle arm. The Cox model-adjusted three-cycle versus the 12-cycle progression hazard ratio was estimated to be 2.31 (99% confidence interval, 1.08 to 4.94). With a protocol-specified early termination boundary of P =.005, these findings led the Southwest Oncology Group Data Safety Monitoring Committee to discontinue the trial. As of the date of study closure, there was no difference in overall survival between the treatment arms. CONCLUSION: Twelve cycles of single-agent paclitaxel administered to women with advanced ovarian cancer who attain a clinically defined complete response to initial platinum/paclitaxel-based chemotherapy significantly prolongs the duration of PFS.

Aged↗
PubMed1995

Carotid endarterectomy for patients with asymptomatic internal carotid artery stenosis. National Institute of Neurological Disorders and Stroke.

On September 28, 1994, the investigators of the Asymptomatic Carotid Atherosclerosis Study (ACAS) reported the interim results of a randomized controlled clinical trial of carotid endarterectomy in patients who have asymptomatic carotid stenosis of greater than 60% reduction in diameter. In addition to aspirin and aggressive management of modifiable risk factors, one-half of the patients were randomly assigned to receive surgery after angiographic confirmation of the lesion. Carotid endarterectomy is beneficial with a statistically significant absolute reduction of 5.8% in the risk of the primary end point of stroke within 5 years and a relative risk reduction of 55%. As a consequence of the trial reaching statistical significance in favor of endarterectomy, and on the recommendation of the study's data monitoring committee, physicians participating in the study were immediately notified and advised to reevaluate patients who did not receive surgery. It is important to note that the success of the operation is dependent on medical centers and surgeons who have a documented perioperative morbidity and mortality of less than 3%, careful selection of patients, and postoperative management of modifiable risk factors.

Adult↗