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Results for “Clinical Trials Data Monitoring Committees”

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At least 127 records · Page 7Linked to original sources
PubMed2007

Predictive probability of success and the assessment of futility in large outcomes trials.

We consider a class of futility rules based on a Bayesian approach for computing the predictive probability of success for large clinical trials, given a certain amount of observed data. This paper focuses on outcomes trials in particular, thus we are concerned with binary response variables. The proposed method determines the likelihood of observing a statistically significant treatment effect at the end of a study, conditional on the data observed at an interim time point and assuming that event rates governing future observations follow beta distributions. In particular, the prior distributions for the event rates of interest are updated based on the observed data at an interim time point, such that means and variances are intuitive functions of the data. Computational aspects will be discussed for the case in which event counts are functions of sample size and event rates only, and for situations in which they are functions of sample size, event rates, and exposure duration. We will discuss appropriate thresholds for declaring futility based on this approach, and the potential impact of overdispersion, a common phenomenon particularly in global outcomes trials.

Algorithms↗
PubMed1999

Data monitoring committees and interim monitoring guidelines.

Most large randomized clinical trials have a data monitoring committee that periodically examines efficacy and safety results. A typical data monitoring committee meets every 6 months, but the interim monitoring guidelines for many trials specify formal analyses that are years apart. In this article we argue that study protocols should include monitoring guidelines with formal looks at each data monitoring committee meeting. Such guidelines are shown to reduce the average duration of a trial with negligible effect on power and estimation bias. Some of the common statistical monitoring guidelines require extreme evidence to stop a trial early and do not distinguish between stopping a trial during active accrual and follow-up stages. We propose practical solutions for these issues.

Bayes Theorem↗
PubMed2005

Module five: implementation of ethics review.

The objective of this module is to inform you on issues of concern for Research Ethics Committee members and investigators during the review process. The many guidelines on research ethics, including those from the South African Department of Health and the World Health Organisation, will be referred to extensively to educate you on the requirements of Research Ethics Committees. The evolution of the review process in South Africa will be detailed.

Advisory Committees↗
PubMed2004

Strength of accumulating evidence and data monitoring committee decision making.

The data monitoring committee (DMC) is a vital component of a randomized clinical trial. Its responsibilities include stopping the trial early for extreme results. The decision to stop the trial must be based on a careful synthesis of statistical methodology and clinical judgment. It is critical to ensure the validity of this complex process. In this paper we present results of a survey of 21 DMC members conducted to investigate how they evaluate accumulating evidence. The results indicate that some DMC members may be over-interpreting developing trends in the data.

Antineoplastic Agents↗
PubMed2004

Pharmacoepidemiology 101: data monitoring committees in the post-marketing approval setting.

The development of the risk management paradigm for the enhancement of post-marketing approval drug safety carries with it the need for external monitoring of the different approaches used by the sponsor. The concept of a Data Monitoring Committee (DMC), widely used in the management of randomized clinical trials, is adapted to provide this monitoring function. The rationale for the post-marketing approval DMC is considered in the context of the risk management paradigm, as well as in the more traditional post-marketing approval surveillance setting. The composition and operation of the post-marketing approval DMC are considered, as well as the process of implementing the committee. Although the adaptation proposed in this article is focused on the paradigm proposed by the United States Food and Drug Administration, it is likely that it will require modification as risk management is adopted (and adapted) by other health regulators.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

The brain tumor board: lessons to be learned from an interdisciplinary conference.

BACKGROUND: The aim of this study is to analyze the work of the interdisciplinary Brain Tumor Board (BTB) which was established at Freiburg University Hospital in 1998. PATIENTS AND METHODS: From January 1998 to December 2003, a total of 1,516 patients were discussed in 259 meetings of the BTB. The protocols of the BTB were analyzed retrospectively. RESULTS: In 79% of the patients, the diagnosis was based on histological findings or a typical radiological appearance of a lesion, or both. This group was composed of 4 subgroups: 28% benign skull base tumors (19% meningiomas, 4% pituitary adenomas, 3% acoustic schwannomas, 2% others), 24% primary brain tumors of glial origin (8% glioblastomas, 12% gliomas other than glioblastomas, 5% oligoastrocytomas or oligodendrogliomas), 19% brain metastases, and 8% other brain or skull base tumors. In 13% of the cases, the exact diagnosis was still unknown when the patient was presented. 8% of the presentations were motivated by nontumorous interdisciplinary problems (e.g. arterio-venous malformations). The recommendations given by the BTB included: 23% further diagnostic procedures (11% non-invasive examinations, 12% stereotactic biopsies), 57% active antitumoral therapy (22% resection, 17% fractionated radiotherapy, 13% radiosurgery, 5% chemotherapy, <1% embolization), 20% no treatment (14% watchful waiting, 6% supportive care). 91% of the BTB recommendations were realized within 3 months. CONCLUSION: Interdisciplinary care seems to be particularly necessary in patients with benign skull base tumors, gliomas and brain metastases. Decisions made in a small interdisciplinary group of experts have a high potential of subsequently being realized.

Academic Medical Centers↗
PubMed1998

Monitoring data and safety in the WHO Antenatal Care Trial.

A committee to monitor data and safety in a large clinical trial should have members with expertise in biostatistics, epidemiology and the clinical field relevant to the trial. Its mandate should cover both logistics and the safety of study subjects, issues which to some extent overlap. While a steering committee and field staff members ideally should be blinded to the experimental and control arms of a randomised clinical trial, the data and safety monitoring committee (DSMC) should have full access to interim trial data to fulfil its role as watchdog. One initial question to be resolved concerns if and when to advise stopping a trial because of danger to study subjects, or on the other hand obvious benefits, in one trial arm. The DSMC of the WHO Antenatal Care Trial decided not to establish any definite stopping rules before implementation. After a scrutiny of the adopted procedures for data collection and handling, the DSMC received monthly reports of recruitment, and individual summary reports of three adverse events by site and trial arm: maternal deaths, fetal deaths and cases of eclampsia. At the time of writing (December 1997) recruitment to the trial is almost complete, but data collection will continue throughout most of 1998, until every index pregnancy has ended in birth or miscarriage. So far, the balance of untoward events between the intervention and control arms have not given cause for alarm.

Argentina↗
PubMed2005

[DSMB. 1. What role, what responsibilities?].

In addition to the IRB (Institutional review board), the DSMB (data safety and monitoring board) takes an increasing role in the monitoring of clinical trials, especially in large multicenter trials. The DSMB is a an expert committee, independent from the investigators and the sponsor of the trial, which periodically examines the safety data accumulated during progress of the trial and ensures that the benefit/risk ratio remains acceptable for participating patients. The DSMB is also a safeguard for the scientific integrity of the trial. It is the only committee which can have access to unblinded data from the trial. The DSMB may recommend termination of the trial in three situations : (1) occurrence of unanticipated adverse events which may pose a serious risk for participating patients; (2) demonstration of efficacy before the planned accrual \; (3) and because of "futility" (the most difficult situation), i.e. in absence of a reasonable probability that the trial may reach a conclusion within its planned frame.

Clinical Trials Data Monitoring Committees↗
PubMed2006

The other side of clinical trial monitoring; assuring data quality and procedural adherence.

BACKGROUND: Data monitoring can mean different things. It can mean statistical methodologies for clinical trial monitoring, interim data analysis, monitoring for quality control or assurance or safety reporting to regulatory agencies. PURPOSE: The various facets of data monitoring will be discussed and reviewed from primarily an industry perspective. METHODS: By careful attention to the design and conduct of a clinical trial, the expense of monitoring can be markedly reduced. Careful attention should be given to the qualifications of investigators in the selection of clinical sites and central facilities. Site personnel must be adequately trained. The sponsor should utilize appropriately qualified individuals to supervise the overall conduct of the trial. The monitor should visit the investigator at the site of the investigation frequently enough to ensure acceptable quality. The monitor is responsible for inspecting the case report forms at regular intervals. Quality control should be applied to each stage of data handling to ensure that all data are reliable and have been processed correctly. The auditor will assess whether the site is being monitored in accordance with the monitoring plan. The determination of the extent and nature of monitoring should be based on considerations such as the objective, design and complexity of the trial. Statistical sampling may be an acceptable method for selecting the data to be verified. The monitor should ensure that adverse events are reported. Study data will be monitored on an ongoing basis to ensure patient safety. The sponsor may utilize a Data Monitoring Committee to protect the validity of a trial. CONCLUSIONS: Discussions between industry, academia and regulatory groups regarding the optimal extent and methods for monitoring of clinical trials are encouraged.

Adverse Drug Reaction Reporting Systems↗
PubMed2004

The data monitoring experience in the MOXCON trial.

AIMS: This article describes a challenging data monitoring experience that occurred in a major international randomized placebo-controlled trial in patients with heart failure, in which the accumulating interim data showed an excess of deaths on the active treatment. METHODS AND RESULTS: The MOXonidine CONgestive Heart Failure trial was a randomized comparison of moxonidine, a central sympathetic inhibitor, with placebo. It was planned to recruit 4500 patients with heart failure. The primary endpoint was all-cause mortality, and average follow-up was anticipated to be around 2.5 years until 724 deaths occurred. The trial Data Monitoring Board (DMB) was to conduct safety monitoring reviews of interim data at least every six months, and make their recommendations to the Executive Committee. Within a few months of the study starting, the Data Monitoring Board (DMB) observed an emerging trend of an excess of deaths on moxonidine compared with placebo. This article describes the sequence of events that unfolded: several DMB meetings to evaluate the accumulating evidence, a DMB recommendation to stop the trial, consequent dialogue with the Executive Committee and sponsor leading to a final decision to stop the trial. Ten months after the first patient was randomized, the study was stopped based on 46 versus 25 deaths in 990 moxonidine and 943 placebo patients, respectively, P=0.01. The final published evidence had 54 versus 32 deaths, P=0.012. CONCLUSIONS: This study illustrates the problems faced by a DMB, and subsequently the trial Executive Committee and sponsor, in deciding how to act in the face of an emerging (and agonizing) negative trend for mortality in a major international trial.

Clinical Trials Data Monitoring Committees↗
PubMed2003

Be skeptical about unexpected large apparent treatment effects: the case of an MRC AML12 randomization.

The preliminary results of the twelfth Medical Research Council acute myeloid leukemia trial show no evidence of a survival advantage for five courses of therapy compared to four courses in a randomized comparison involving 1078 patients (hazard ratio 1.09, 95% confidence interval [CI] 0.87-1.37, p=0.4). However, the data presented to the independent data monitoring and ethics committee (DMEC) at both its reviews in 1998 suggested large benefits for the additional course with hazard ratios of 0.47 and 0.55 (95% CIs 0.29-0.77 and 0.38-0.80, p=0.003 and p=0.002, respectively). Despite these highly significant findings, the DMEC did not recommend closure of the randomization, a decision vindicated by the subsequent reversion to a null result. The main reason for not closing the randomization was that the treatment effects observed in 1998 (53% and 45% reductions in the odds of death) were considered too large to be clinically plausible, despite the p-values associated with them. Investigations have not identified any clinical explanations, such as different types of patients in the early and later parts of the trial, to explain the loss of benefit as the trial progressed. Thus, the most likely current explanation for the large benefit observed early on is the play of chance. Lessons to be learned from this example are that: fixed stopping rules based on some predetermined p-value should not be used and the decision to close a randomization or not should take account of other factors such as the medical plausibility of the magnitude of the treatment effect; chance effects do occur and happen more frequently than many clinicians realize; it is important that DMEC members are experienced in the interpretation of clinical trial evidence and aware of the dangers of early stopping without wholly convincing evidence.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Methodology of therapeutic trials: lessons from the late evidence of the cardiovascular toxicity of some coxibs.

The removal of rofecoxib after several years on the market has caused deep concern among patients, physicians, researchers, editors, and regulatory agencies. Similar situations have occurred in the recent past. They illustrate the serious limitations of preregistration trials. Approved drugs should be subjected to close postmarketing surveillance. A number of methodological issues regarding the evaluation of drug safety are discussed in this article. The advantages and drawbacks of observational studies and randomized trials are reviewed. Emphasis is put on the usefulness of independent steering committees for therapeutic trials and on the value of cumulative meta-analyses.

Clinical Trials Data Monitoring Committees↗
PubMed2003

Statistical issues related to early closure of STOP-ROP, a group-sequential trial.

The Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity trial used the group-sequential alpha-spending approach with asymmetrical tails to investigate whether supplemental oxygen therapy would reduce the proportion of infants progressing from prethreshold retinopathy of prematurity (ROP) to threshold ROP from 30% to 20%. Three years of enrollment were predicted. After 4 years, the data and safety monitoring committee (DSMC), faced with a projected delay of 2-3 more years, opted to terminate the trial after 1 further year of enrollment despite a continually borderline test statistic. We discuss factors relating to the DSMC decision and its effect upon the conclusions that may be drawn from the trial.

Clinical Trials Data Monitoring Committees↗