Article
Medicine, General & Internal
Charis Wong, Rachel S. Dakin, Jill Williamson, Judith Newton, Michelle Steven, Shuna Colville, Maria Stavrou, Jenna M. Gregory, Elizabeth Elliott, Arpan R. Mehta, Jeremy Chataway, Robert J. Swingler, Richard Anthony Parker, Christopher J. Weir, Nigel Stallard, Mahesh K. B. Parmar, Malcolm R. Macleod, Suvankar Pal, Siddharthan Chandran
Summary: MND-SMART is a multi-arm, multi-stage, adaptive trial aimed at efficiently evaluating the efficacy of drugs. The trial design reduces time, cost, and participant numbers, while minimizing the risk of participants receiving ineffective treatments.
Article
Mathematical & Computational Biology
Lauren Kanapka, Anastasia Ivanova
Summary: This article discusses a multi-arm trial design with multiple active treatments and a control group. By assuming a certain order for the treatment effects, the objective is to compare each active treatment to the control group while maintaining control of the type 1 error rate. The results show that using the order of treatment effects to calculate the test statistic and set the testing order can reduce the sample size by at least 20% compared to testing each active treatment against the control independently.
STATISTICS IN MEDICINE
(2023)
Article
Mathematical & Computational Biology
Alessandra Serra, Pavel Mozgunov, Thomas Jaki
Summary: Multi-arm multi-stage (MAMS) designs can improve efficiency by studying multiple treatment arms concurrently, dropping poorly performing arms early, and incorporating the order of treatment effects without assuming parametric models. The design efficiently identifies promising treatments with strong control of the family-wise error rate. By including ordering information, it leads to better decision-making compared to fixed sample and conventional MAMS designs, achieving reductions in sample size of around 15% in considered settings.
STATISTICS IN MEDICINE
(2022)
Review
Medicine, General & Internal
Nurulamin M. Noor, Sharon B. Love, Talia Isaacs, Richard Kaplan, Mahesh K. B. Parmar, Matthew R. Sydes
Summary: Historically, late-phase trials have typically used standard two-arm designs, but there has been an increasing trend in late-phase MAMS platform trials since 2001, with acceleration due to the impact of COVID-19. The majority of current MAMS platforms target either infectious diseases (52%) or cancers (29%), and all identified trials focus on treatment interventions. Medications are the main focus of evaluation in 89% of the MAMS platforms, with 45% including repurposed medications as comparison arms. This study highlights the growing prevalence of MAMS platform trials in late-phase settings and their potential for various disease areas.
Article
Clinical Neurology
Tom Foltynie, Sonia Gandhi, Cristina Gonzalez-Robles, Marie-Louise Zeissler, Georgia Mills, Roger Barker, James Carpenter, Anette Schrag, Anthony Schapira, Oliver Bandmann, Stephen Mullin, Joy Duffen, Kevin McFarthing, Jeremy Chataway, Mahesh Parmar, Camille Carroll
Summary: Multi-arm, multi-stage platform designs have improved the efficiency of clinical trials in the field of oncology. Foltynie et al. discuss the challenges and considerations of using this approach to assess potential disease-modifying treatments in progressive neurological conditions such as Parkinson's disease.
Article
Mathematical & Computational Biology
Jianrong Wu, Yimei Li, Liang Zhu
Summary: A multi-arm trial allows simultaneous comparison of multiple experimental treatments with a common control, improving efficiency compared to traditional randomized controlled trials. This paper presents a group sequential multi-arm multi-stage (MAMS) trial design based on the sequential conditional probability ratio test, providing analytical solutions for futility and efficacy boundaries for an arbitrary number of stages and arms.
STATISTICS IN MEDICINE
(2023)
Article
Mathematical & Computational Biology
Suzanne M. Dufault, Angela M. Crook, Katie Rolfe, Patrick P. J. Phillips
Summary: We propose a multi-metric flexible Bayesian framework for efficient interim decision-making in multi-arm multi-stage phase II clinical trials. Based on simulation studies using a motivating example of a large public-private partnership targeting novel TB arms, our framework provides sufficient confidence for decision-making with sample sizes as low as 30 patients per arm, even when intermediate outcomes have only moderate correlation with the primary outcome.
STATISTICS IN MEDICINE
(2023)
Article
Mathematical & Computational Biology
Alessandra Serra, Pavel Mozgunov, Thomas Jaki
Summary: This study proposes a Bayesian multi-arm multi-stage trial design that efficiently selects promising treatments and incorporates information about the order in treatment effects and prior knowledge. The design allows for uncertainty in treatment effect order assumption and does not assume any parametric arm-response model.
STATISTICS IN MEDICINE
(2023)
Article
Dermatology
Matthew A. Popplewell, Brenig L. Gwilym, Ruth A. Benson, Maciej Juszczak, David Bosanquet, Thomas D. Pinkney, Ian Chetter, Michael Wall
Summary: A survey was conducted among vascular clinicians to assess their opinion and practice on interventions to prevent groin wound surgical site infection (SSI) following arterial surgery. The majority of participants believed that groin wound SSI is a major problem and expressed willingness to use the proposed interventions. There was clinical equipoise in randomizing patients to any of the interventions versus standard care, although some reluctance was observed regarding the use of impregnated incise drapes.
INTERNATIONAL WOUND JOURNAL
(2023)
Article
Medicine, General & Internal
Benjamin Y. Kong, Hao-Wen Sim, Elizabeth H. Barnes, Anna K. Nowak, Elizabeth J. Hovey, Rosalind Jeffree, Rosemary Harrup, Jonathon Parkinson, Hui K. Gan, Mark B. Pinkham, Sonia Yip, Merryn Hall, Emily Tu, Candace Carter, Eng-Siew Koh, Zarnie Lwin, Anthony Dowling, John S. Simes, Craig Gedye
Summary: The MAGMA trial aims to test the effectiveness of different interventions designed to improve the survival rate of GBM patients. Newly diagnosed GBM patients are recruited to compare surgical resection followed by chemoradiotherapy with adjuvant chemotherapy alone or with additional neoadjuvant or extended chemotherapy.
Review
Medicine, Research & Experimental
Elias Laurin Meyer, Peter Mesenbrink, Tobias Mielke, Tom Parke, Daniel Evans, Franz Koenig
Summary: In recent years, the popularity of platform trials has increased, but there are still many design-related questions that need further exploration. Existing software packages often target single design elements and lack extensive design flexibility. Collaborative efforts are needed to create software that fully utilizes the flexibility of platform trials.
Article
Oncology
Nicholas D. James, Noel W. Clarke, Adrian Cook, Adnan Ali, Alex P. Hoyle, Gerhardt Attard, Christopher D. Brawley, Simon Chowdhury, William R. Cross, David P. Dearnaley, Johann S. de Bono, Carlos Diaz-Montana, Duncan Gilbert, Silke Gillessen, Clare Gilson, Rob J. Jones, Ruth E. Langley, Zafar I. Malik, David J. Matheson, Robin Millman, Chris C. Parker, Cheryl Pugh, Hannah Rush, J. Martin Russell, Dominik R. Berthold, Michelle L. Buckner, Malcolm D. Mason, Alastair W. S. Ritchie, Alison J. Birtle, Susannah J. Brock, Prantik Das, Dan Ford, Joanna Gale, Warren Grant, Emma K. Gray, Peter Hoskin, Mohammad M. Khan, Caroline Manetta, Neil J. McPhail, Joe M. O'Sullivan, Omi Parikh, Carla Perna, Carmel J. Pezaro, Andrew S. Protheroe, Angus J. Robinson, Sarah M. Rudman, Denise J. Sheehan, Narayanan N. Srihari, Isabel Syndikus, Jacob S. Tanguay, Carys W. Thomas, Salil Vengalil, John Wagstaff, James P. Wylie, Mahesh K. B. Parmar, Matthew R. Sydes
Summary: Abiraterone acetate plus prednisolone improves overall survival in prostate cancer patients receiving long-term hormone therapy, regardless of metastatic disease risk group.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Public, Environmental & Occupational Health
Jill E. Luoto, Italo Lopez Garcia, Frances E. Aboud, Daisy R. Singla, Lia C. H. Fernald, Helen O. Pitchik, Uzaib Y. Saya, Ronald Otieno, Edith Alu
Summary: This study demonstrates that parenting interventions delivered by trained community health volunteers in mother-child groups can effectively promote child development in low-resource settings, with great potential for scalability.
LANCET GLOBAL HEALTH
(2021)
Article
Medicine, Research & Experimental
Richard A. A. Parker, Christopher J. J. Weir, Tra My Pham, Ian R. R. White, Nigel Stallard, Mahesh K. B. Parmar, Robert J. J. Swingler, Rachel S. S. Dakin, Suvankar Pal, Siddharthan Chandran
Summary: MND-SMART is a multi-arm, multi-stage, multi-centre randomized controlled trial for motor neuron disease. It compares the efficacy of memantine and trazodone with placebo, and may introduce other investigational treatments later. The co-primary outcomes are ALS-FRS-R functional outcome and overall survival. The trial randomizes participants 1:1:1 to receive placebo or one of the investigational treatments, with a maximum of 531 participants. Comparisons will be conducted in four stages, with the opportunity to stop randomizations to poorly performing arms. The final analysis will be based on a statistical analysis plan finalized in May 2022.
Article
Health Care Sciences & Services
Andrea Bassi, Johannes Berkhof, Daphne de Jong, Peter M. van de Ven
Summary: This paper proposes a generic Bayesian adaptive decision-theoretic design for multi-arm multi-stage clinical trials, which makes decisions about trial continuation based on expected loss reduction. The study shows that this design increases the probability of making a correct decision at the end of the trial compared to nonadaptive and adaptive two-stage designs through simulation.
STATISTICAL METHODS IN MEDICAL RESEARCH
(2021)
