Design of the master protocol platform trial and its application in related fields

The traditional approach to clinical trial design requires assuming precise values for multiple unknown parameters, resulting in a trial design that is unlikely to perform well if one or more of those assumptions turn out to be incorrect. During conduct of the trial, trial characteristics are often held fixed, even if incoming data suggest that one or more design assumptions were incorrect. This leads to an increased risk of a failed trial. In contrast, an adaptive clinical trial is designed to take advantage of partial, incoming data during the conduct of the trial, modifying key clinical trial characteristics according to prespecified rules, in order to avoid a failed or inconclusive trial, improve statistical efficacy, better treat patients within the trial, or achieve other scientific or ethical goals. The concept of an adaptive trial can be expanded to a platform trial, a clinical trial that is intended to evaluate multiple treatments or combinations of treatments, often for patients with any of a group of related diseases, and to continue beyond the evaluation of any particular treatment. Platform trial design strategies can be applied to the problem of finding the best treatment strategy for patients suffering from posttraumatic hemorrhagic shock. We present the rationale and considerations surrounding adaptive and platform trial design and apply these concepts to the problem of investigating strategies for remote damage control resuscitation.

With more than 230,000 new cases each year in the United States, prostate cancer is the most common cancer diagnosed among American men [(1)][1] . Prostate cancer is expected to account for nearly 30,000 deaths in the United States in 2004 and consequently represents the second most common cause of

Randomized Trials Fit for the 21st Century: A Joint Opinion From the European Society of Cardiology, American Heart Association, American College of Cardiology, and the World Heart Federation.

The Bayesian Approach to Clinical Trials and Individualized Cancer Therapy

##### Ovarian Cancer Incidence and Mortality Rates. Ovarian cancer is the fourth leading cause of death from cancer in women and accounts for the highest mortality rate of all of the gynecological cancers [(1)][1] . Despite aggressive treatment via radical surgery, radiotherapy, or chemotherapy,

COVID-19 pandemic and the tension between the need to act and the need to know.

The Role of Patient-reported Outcomes and Medication Adherence Assessment in Patient-focused Drug Development for Solid Organ Transplantation.

The State of Being Noninferior

EPO for stroke therapy - Is there a future for further clinical development?

Defining Endpoints and Biomarkers in Inflammatory Bowel Disease: Moving the Needle Through Clinical Trial Design

One year on: The impact of COVID-19 on clinical research

BackgroundPlatform trial designs are used increasingly in cancer clinical research and are considered an efficient model for evaluating multiple compounds within a single disease or disease subtype. However, these trial designs can be challenging to operationalise.The use of platform trials in oncology clinical research has increased considerably in recent years as advances in molecular biology enable molecularly defined stratification of patient populations and targeted therapy evaluation. Whereas multiple separate trials may be deemed infeasible, platform designs allow efficient, parallel evaluation of multiple targeted therapies in relatively small biologically defined patient sub-populations with the promise of increased molecular screening efficiency and reduced time for drug evaluation. Whilst the theoretical efficiencies are widely reported, the operational challenges associated with these designs (complexity, cost, regulatory, resource) are not always well understood.MainIn this commentary, we describe our practical experience of the implementation and delivery of the UK plasmaMATCH trial, a platform trial in advanced breast cancer, comprising an integrated screening component and multiple parallel downstream mutation-directed therapeutic cohorts. plasmaMATCH reported its primary results within 3 years of opening to recruitment. We reflect on the operational challenges encountered and share lessons learnt to inform the successful conduct of future trials. Key to the success of the plasmaMATCH trial was well co-ordinated stakeholder engagement by an experienced clinical trials unit with expert methodology and trial management expertise, a federated model of clinical leadership, a well-written protocol integrating screening and treatment components and including justification for the chosen structure and intentions for future adaptions, and an integrated funding model with streamlined contractual arrangements across multiple partners. Findings based on our practical experience include the importance of early engagement with the regulators and consideration of a flexible resource infrastructure to allow adequate resource allocation to support concurrent trial activities as adaptions are implemented in parallel to the continued management of patient safety and data quality of the ongoing trial cohorts.ConclusionPlatform trial designs allow the efficient reporting of multiple treatment cohorts. Operational challenges can be overcome through multidisciplinary engagement, streamlined contracting processes, rationalised protocol and database design and appropriate resourcing.

Representative enrolment of older adults in clinical trials: the time is now

Clinical trials are essential to govern the impact of a new possible treatment. It is utilized to determine the safety level and efficacy of a certain treatment. Clinical trial studies in cancer have provided successful treatment leading to longer survival span in the patients. The design of clinical trials for cancer has been done to find new ways to prevent, diagnose, treat, and manage symptoms of the disease. This chapter will provide detailed information on different aspects of clinical trials in cancer research. Protocols outlining the design and method to conduct a clinical trial in each phase will be discussed. The process and the conditions applied in each phase (I, II, and III) will be described precisely. The design of trials done in every aspect such as prevention, immunochemotherapy, diagnosis, and treatment to combat cancer will be illustrated. Also, recent innovations in clinical design strategies and principles behind it as well as the use of recent advances in artificial intelligence in reshaping key steps of clinical trial design to increase trial success rates.

Changing Landscape and Disease-specific Considerations of Therapeutic Bronchoscopy in Clinical Trials