More multiarm randomised trials of superiority are needed

Parmar, Mahesh; Carpenter, James; Sydes, Matthew R.

doi:10.1016/s0140-6736(14)61122-3

Cited by 112 publications

(119 citation statements)

References 14 publications

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“…Such a design would ideally be adaptive, possibly a multiarm (MAMS) umbrella trial that would capture the wider patient group including those with comorbidities. 54 Overall, the SURAB trial had a good safety record, with a low incidence of AEs in both arms of the study and no SAEs recorded in relation to the trial. Statistical analysis of patient-reported and clinician-rated outcomes was not possible owing to the recruitment rate.…”

Section: Feasibility Studymentioning

confidence: 88%

Surveillance versus ablation for incidentally diagnosed small renal tumours: the SURAB feasibility RCT

Soomro

Lecouturier

Stocken

et al. 2017

Health Technol Assess

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Background There is uncertainty around the appropriate management of small renal tumours. Treatments include partial nephrectomy, ablation and active surveillance. Objectives To explore the feasibility of a randomised trial of ablation versus active surveillance. Design Two-stage feasibility study: stage 1 – clinician survey and co-design work; and stage 2 – randomised feasibility study with qualitative and economic components. Methods Stage 1 – survey of radiologists and urologists, and development of patient information materials. Stage 2 – patients identified across eight UK centres with small renal tumours (< 4 cm) were randomised (1 : 1 ratio) to ablation or active surveillance in an unblinded manner. Randomisation was carried out by a central computer system. The primary objective was to determine willingness to participate and to randomise a target of 60 patients. The qualitative and economic data were collected separately. Results The trial was conducted across eight centres, with a site-specific period of recruitment ranging from 3 to 11 months. Of the 154 patients screened, 36 were eligible and were provided with study details. Seven agreed to be randomised and one patient was found ineligible following biopsy results. Six patients (17% of those eligible) were randomised: three patients received ablation and no serious adverse events were recorded. The 3- and 6-month data were collected for four (67%) and three (50%) out of the six patients, respectively. The qualitative substudy identified factors directly impacting on the recruitment of this trial. These included patient and clinician preferences, organisational factors (variation in clinical pathway) and standard treatment not included. The health economic questionnaire was designed and piloted; however, the sample size of recruited patients was insufficient to draw a conclusion on the feasibility of the health economics. Conclusions The trial did not meet the criteria for progression and the recruitment rate was lower than hypothesised, demonstrating that a full trial is presently not possible. The qualitative study identified factors that led to variation in recruitment across the sites. Implementation of organisational and operational measures can increase recruitment in any future trial. There was insufficient information to conduct a full economic analysis. Trial registration Current Controlled Trials ISRCTN31161700. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 81. See the NIHR Journals Library website for further project information.

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Section: Feasibility Studymentioning

confidence: 88%

Surveillance versus ablation for incidentally diagnosed small renal tumours: the SURAB feasibility RCT

Soomro

Lecouturier

Stocken

et al. 2017

Health Technol Assess

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“…An immediate advantage of such an approach over separate two-arm studies is that only a single control group is used. As a consequence, a patient's chance to receive an experimental treatment is increased which has been argued could help with recruiting patients to such studies [5,6]. Additionally, such studies allow a fair, contemporary comparison of different experimental treatments as the comparisons are made against the same control group and under a single protocol so that relevant features of the study, such as inclusion/exclusion criteria, are the same.…”

Section: An Overview Of Different Types Of Multi-arm Studiesmentioning

confidence: 99%

Multi-arm clinical trials with treatment selection: what can be gained and at what price?

Jaki¹

2015

Clinical Investigation

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With current success rates of confirmatory studies being only around 50%, new approaches to drug development are paramount. Many trials fail simply because ineffective treatments are identified too late. In this paper, we discuss the utility of multi-arm studies with treatment selection as a potential strategy that can reduce the high attrition rate. We illustrate the large gains in efficiency that are possible based on an example in Alzheimer's disease while outlining the additional challenges that need to be overcome to implement such studies.

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“…Recognising this deficit, increasingly we are seeing a more radical approach, with a multi-arm design algorithm being employed to maximise benefit [26]. This design is particularly relevant in the context of biomarker-driven cancer clinical trials, which require the simultaneous evaluation of multiple targeted therapies, underpinned by precise biomarker-guided patient selection [27].…”

Section: Cancer Clinical Trials: the Wheel Is Broken - So Let's Fix Itmentioning

confidence: 99%

Personalised and Precision Medicine in Cancer Clinical Trials: Panacea for Progress or Pandora's Box?

Lawler¹,

Sullivan

2015

Public Health Genomics

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Cancer clinical trials have been one of the key foundations for significant advances in oncology. However, there is a clear recognition within the academic, care delivery and pharmaceutical/biotech communities that our current model of clinical trial discovery and development is no longer fit for purpose. Delivering transformative cancer care should increasingly be our mantra, rather than maintaining the status quo of, at best, the often miniscule incremental benefits that are observed with many current clinical trials. As we enter the era of precision medicine for personalised cancer care (precision and personalised medicine), it is important that we capture and utilise our greater understanding of the biology of disease to drive innovative approaches in clinical trial design and implementation that can lead to a step change in cancer care delivery. A number of advances have been practice changing (e.g. imatinib mesylate in chronic myeloid leukaemia, Herceptin in erb-B2-positive breast cancer), and increasingly we are seeing the promise of a number of newer approaches, particularly in diseases like lung cancer and melanoma. Targeting immune checkpoints has recently yielded some highly promising results. New algorithms that maximise the effectiveness of clinical trials, through for example a multi-stage, multi-arm type design are increasingly gaining traction. However, our enthusiasm for the undoubted advances that have been achieved are being tempered by a realisation that these new approaches may have significant cost implications. This article will address these competing issues, mainly from a European perspective, highlight the problems and challenges to healthcare systems and suggest potential solutions that will ensure that the cost/value rubicon is addressed in a way that allows stakeholders to work together to deliver optimal cost-effective cancer care, the benefits of which can be transferred directly to our patients.

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More multiarm randomised trials of superiority are needed

Cited by 112 publications

References 14 publications

Surveillance versus ablation for incidentally diagnosed small renal tumours: the SURAB feasibility RCT

Surveillance versus ablation for incidentally diagnosed small renal tumours: the SURAB feasibility RCT

Multi-arm clinical trials with treatment selection: what can be gained and at what price?

Personalised and Precision Medicine in Cancer Clinical Trials: Panacea for Progress or Pandora's Box?

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