Sample size calculation in randomised phase II selection trials using a margin of practical equivalence

Dehbi, Hakim‐Moulay; Hackshaw, Allan

doi:10.1186/s13063-020-04248-8

Cited by 14 publications

(13 citation statements)

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“…The calculation of the required sample size for this second phase is currently a matter of ongoing research in our group. Dehbi and Hackshaw 16 have published on sample size calculation for binary endpoints in selection trials. This method may be extended to categorical endpoints.…”

Section: Discussionmentioning

confidence: 99%

Early phase dose‐finding trials in virology

Dehbi

Lowe

O’Quigley

2020

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Little has been published in terms of dose-finding methodology in virology. Aside from a few papers focusing on HIV, the considerable progress in dose-finding methodology of the last 25 years has focused almost entirely on oncology. While adverse reactions to cytotoxic drugs may be life threatening, for anti-viral agents we anticipate something different: side effects that provoke the cessation of treatment. This would correspond to treatment failure. On the other hand, success would not be yes/no but would correspond to a range of responses, from small, no more than say 20% reduction in viral load to the complete elimination of the virus. Less than total success matters since this may allow the patient to achieve immune-mediated clearance. The motivation for this article is an upcoming dose-finding trial in chronic norovirus infection. We propose a novel methodology whose goal is twofold: first, to identify the dose that provides the most favorable distribution of treatment outcomes, and, second, to do this in a way that maximizes the treatment benefit for the patients included in the study. K E Y W O R D S continual reassessment method, coronavirus, dose-finding, early phase trials, norovirus, virology 1 INTRODUCTION This introduction has three subsections: the first provides a broad description of our goals, the second a summary of the study motivating this current work, and, finally, a subsection making these goals more specific and anticipating the section that follows on statistical methodology. 1.1 Background and motivation Antiviral agents can fail to be of benefit to a patient in two different ways. The first is where the toxic side effects are such that the patient is unable to take the full course of treatment, thereby not being in a position to experience treatment benefit. The second type of failure is where the treatment is well tolerated but fails to achieve a meaningful clinical or virological effect, for example, a lessening of symptoms, reduction in viral load, or complete elimination of the virus (or, for some viruses, induction of viral latency). When viral load is the main focus, efficacy may be categorized into three or possibly more outcomes, ranging from a small, insignificant reduction in viral load to a large reduction or total elimination (or suppression) of the virus. Given a new candidate treatment, and some range of possible treatment levels, This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Section: Discussionmentioning

confidence: 99%

Early phase dose‐finding trials in virology

Dehbi

Lowe

O’Quigley

2020

Statistics in Medicine

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“…DASS-42 is a self-report questionnaire that measures depression, anxiety, and stress [18]. It was designed in 1997 and has been used repeatedly in different research programs [19].…”

Section: The Scale Of Depression Anxiety and Stress (Dass-42)mentioning

confidence: 99%

Effectiveness of a Need-Based Program in Relieving Psychological Distress of Family Caregivers of Leukemia Patients: A Randomized Clinical Trial

Abdullahzadeh

Khosravi

2021

Preprint

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PurposeThe family of leukemia patients, due to their caring role, often feel psychological distress. This paper describes the efficacy of a designed family-need-based program on relieving depression, anxiety, and stress of family caregivers of leukemia patients by meeting the specific psychological needs of caregivers.MethodsIn this clinical trial, 64 family caregivers of leukemia patients referring to a medical center in Iran were recruited by convenience sampling and divided into study and control groups randomly. The study group attended a designed need-based program. The control group did not receive the intervention. Stress, anxiety, and depression before, right after, and one month after the intervention in family caregivers were compared using DASS-42. Data were analyzed using descriptive and inferential statistics; the significance level adopted was 5%.ResultsBefore the intervention, the mean score of depression, anxiety, and stress scale in both study and control groups showed no considerable difference (P > 0.05). After the intervention, the mean score of DASS-42 revealed a significant difference between the two groups and the study group did better on outcomes (P < 0.001).ConclusionThis family-need-based program can decrease the level of stress, anxiety, and depression of the family caregivers of leukemia patients and may potentially alleviate the psychological distress of family caregivers over their caring role.Trial registration number: IRCT2013093011895N2. Date of registration: 2014-05-06

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“…This being said, in advanced and/or rare cancers where the prognosis is poor, median OS may be expressed in weeks or months. In this article, we extend the methodology of our previous publication 6 to time-to-event endpoints. The aim is to enable selection trials having OS or PFS as their primary endpoint.…”

Section: Introductionmentioning

confidence: 99%

“…When selecting among competing options, efficacy may not be the only relevant factor, especially when the observed efficacy levels are very similar. To remedy this, the concept of a margin of practical equivalence (MPE) in selection trials was first described by Sargent and Goldberg, 5 and then more fully characterized by Dehbi and Hackshaw 6 . The margin determines the amount of additional efficacy that is required so that one of the options can be selected on efficacy grounds alone (assuming that the toxicity profile remains acceptable, and that the observed efficacy is satisfactory with respect to some external/historical minimum threshold).…”

Section: Introductionmentioning

confidence: 99%

“…To remedy this, the concept of a margin of practical equivalence (MPE) in selection trials was first described by Sargent and Goldberg, 5 and then more fully characterized by Dehbi and Hackshaw. 6 The margin determines the amount of additional efficacy that is required so that one of the options can be selected on efficacy grounds alone (assuming that the toxicity profile remains acceptable, and that the observed efficacy is satisfactory with respect to some external/historical minimum threshold). If the observed efficacy levels are within the pre-specified MPE, then additional dimensions such as toxicity, quality of life, and cost are evaluated to make the selection.…”

Section: Introductionmentioning

confidence: 99%

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Sample size calculation for randomized selection trials with a time‐to‐event endpoint and a margin of practical equivalence

Dehbi

Embleton‐Thirsk

McCaw³

2022

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Selection trials are used to compare potentially active experimental treatments without a control arm. While sample size calculation methods exist for binary endpoints, no such methods are available for time-to-event endpoints, even though these are ubiquitous in clinical trials. Recent selection trials have begun using progression-free survival as their primary endpoint, but have dichotomized it at a specific time point for sample size calculation and analysis. This changes the clinical question and may reduce power to detect a difference between the arms. In this article, we develop the theory for sample size calculation in selection trials where the time-to-event endpoint is assumed to follow an exponential or Weilbull distribution. We provide a free web application for sample size calculation, as well as an R package, that researchers can use in the design of their studies.

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Sample size calculation in randomised phase II selection trials using a margin of practical equivalence

Cited by 14 publications

References 10 publications

Early phase dose‐finding trials in virology

Early phase dose‐finding trials in virology

Effectiveness of a Need-Based Program in Relieving Psychological Distress of Family Caregivers of Leukemia Patients: A Randomized Clinical Trial

Sample size calculation for randomized selection trials with a time‐to‐event endpoint and a margin of practical equivalence

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