Topics

Estimation of treatment effects following a sequential trial of multiple treatments.

08:00 EDT 23rd March 2020 | BioPortfolio

Summary of "Estimation of treatment effects following a sequential trial of multiple treatments."

When a clinical trial is subject to a series of interim analyses as a result of which the study may be terminated or modified, final frequentist analyses need to take account of the design used. Failure to do so may result in overstated levels of significance, biased effect estimates and confidence intervals with inadequate coverage probabilities. A wide variety of valid methods of frequentist analysis have been devised for sequential designs comparing a single experimental treatment with a single control treatment. It is less clear how to perform the final analysis of a sequential or adaptive design applied in a more complex setting, for example, to determine which treatment or set of treatments amongst several candidates should be recommended. This article has been motivated by consideration of a trial in which four treatments for sepsis are to be compared, with interim analyses allowing the dropping of treatments or termination of the trial to declare a single winner or to conclude that there is little difference between the treatments that remain. The approach taken is based on the method of Rao-Blackwellization which enhances the accuracy of unbiased estimates available from the first interim analysis by taking their conditional expectations given final sufficient statistics. Analytic approaches to determine such expectations are difficult and specific to the details of the design: instead "reverse simulations" are conducted to construct replicate realizations of the first interim analysis from the final test statistics. The method also provides approximate confidence intervals for the differences between treatments.

Affiliation

Journal Details

This article was published in the following journal.

Name: Statistics in medicine
ISSN: 1097-0258
Pages:

Links

DeepDyve research library

PubMed Articles [40741 Associated PubMed Articles listed on BioPortfolio]

Dynamic treatment regimens in small n, sequential, multiple assignment, randomized trials: An application in focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a rare kidney disease with an annual incidence of 0.2-1.8 cases per 100,000 individuals. Most rare diseases like FSGS lack effective treatments, and it is ...

Study protocol for a sequential multiple assignment randomized trial (SMART) to improve physical activity in employed women.

Physical activity monitors, motivational text messages, group meetings and personal calls have proven to be efficacious physical activity interventions. However, individual participant response to the...

In Situ Generation of Chlorine Dioxide for Decontamination of and Pathogenic on Cantaloupes, Mung Beans, and Alfalfa Seeds.

In situ generation of chlorine dioxide to reduce microbial populations on produce surfaces has been shown to be effective on produce models. This study examined the treatment for decontamination of ba...

Modeling pupil responses to rapid sequential events.

Pupil size is an easily accessible, noninvasive online indicator of various perceptual and cognitive processes. Pupil measurements have the potential to reveal continuous processing dynamics throughou...

Treatment for Borderline Personality Disorder and Secondary Effects on Somatization.

Borderline personality disorder (BPD) is often accompanied by other diagnoses. Some comorbidities have received a good deal of attention, but others, including somatization, have not. As effective tre...

Clinical Trials [14406 Associated Clinical Trials listed on BioPortfolio]

Therapeutic Trial Comparing Empiric Sequential Treatment vs Sequential Treatment Guided by the Determination of the Resistance to Clarithromycin by PCR vs. Quadruple Bismuth Therapy for Helicobacter Pylori Infection

The main objective is to compare the efficacy of sequential empirical treatment (eradication rate 80% hypothesized) with the sequential therapy guided by the results of a PCR test (eradica...

Difference in the Estimation of Prognosis

The primary objective is to identify the difference in the estimation of prognosis of advanced cancer patients between medical oncologists and palliative care physicians.

SMART Weight Loss Management

The overall objective of this study is to use an innovative experimental approach, the SMART (Sequential Multiple Assignment Randomized Trial), to determine the best way to sequence the de...

A Efficacy and Tolerability Study of TEGAFOX Sequential S-1 in the Treatment of Adjuvant Chemotherapy for Gastric Cancer

This study is designed to compare the three chemotherapy regimens(TEGAFOX Sequential S-1 or SOX Sequential S-1 or SOX non-Sequential S-1) for postoperative patients with gastric cancer, ob...

National Multicenter, Controlled, Single-blind Study With Two Parallel Groups Evaluating the Safety and Efficacy of Sequential Treatment With Mitoxantrone and Interferon Versus Interferon Alone in Patients With Strong Risk of Progression in the Initial Ph

The relative effectiveness of current treatments and their different mechanisms of action yield to consider more and more that the multiple sclerosis (MS) therapeutic approach must use mul...

Medical and Biotech [MESH] Definitions

Work consisting of a clinical trial involving one or more test treatments, at least one control treatment, specified outcome measures for evaluating the studied intervention, and a bias-free method for assigning patients to the test treatment. The treatment may be drugs, devices, or procedures studied for diagnostic, therapeutic, or prophylactic effectiveness. Control measures include placebos, active medicine, no-treatment, dosage forms and regimens, historical comparisons, etc. When randomization using mathematical techniques, such as the use of a random numbers table, is employed to assign patients to test or control treatments, the trial is characterized as a RANDOMIZED CONTROLLED TRIAL.

Work consisting of a clinical trial that involves at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table.

Providing an investigational therapy to a patient who is not eligible to receive that therapy in a clinical trial, but who has a serious or life-threatening illness for which other treatments are not available. Compassionate use trials allow patients to receive promising but not yet fully studied or approved therapies when no other treatment option exists. Also called expanded access trial.

Trial that aims to show a new treatment is no better and no worse than the standard treatment.

Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)

Quick Search


DeepDyve research library

Relevant Topics

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...

Sepsis, septicaemia and blood poisoning
Septicaemia (another name for blood poisoning) refers to a bacterial infection of the blood, whereas sepsis can also be caused by viral or fungal infections.  Sepsis is not just limited to the blood and can affect the whole body, including the organ...


Searches Linking to this Article