Platform trial design
Platform trial design. The inherent complexity of the platform trial design and the multiplicity of the stakeholders invested, which may have different objectives and constraints depending on the arm, reinforces the need to seek these early opinions. The proposed trial design may be applicable for other pathogens against which effective vaccines are not yet available. Jan 20, 2022 · As chaotic as the early pandemic was, it also spurred tremendous innovation in clinical trial design. HOW DO PLATFORM TRIALS DIFFER? Platform trials are different in that they are open ended, meaning new interventions can be added, assessed, and removed as time goes on, without having to specify what they might be at the start. We provide reader's guide to platform trials with a critical appraisal checklist. 1, plasmaMATCH trial design) is a multiple-parallel cohort, open-label, multi-centre phase IIa platform clinical trial with an integrated molecular screening component aiming to provide proof of principle activity for designated targeted therapies in patients with The efficiency of design is a central advantage of platform trials, as it allows for biomarker strata to be run in parallel to study different investigational targets and make changes to interventions as time progresses. Jun 15, 2023 · The NCI-MATCH (Molecular Analysis for Therapy Choice) trial ( NCT02465060 ) was launched in 2015 as a genomically driven, signal-seeking precision medicine platform trial—largely for patients Mar 17, 2017 · The US Food and Drug Administration (FDA) guidance on adaptive clinical trials defined them as “a study that includes a prospectively planned opportunity for modification of one or more specified aspects of the study design and hypotheses based on analysis of data (usually interim data) from subjects in the study. Mar 9, 2020 · Platform trials are an emerging concept that is gaining in popularity, as it has the capability of saving costs through smart trial design. 6%). Gajewski1, Jo Wick 1, Jonathan Beall2, Jerey L. Part of that may be due to Feb 1, 2020 · To save patient resources and improve Phase III efficiency, it may be advantageous for the company to develop an adaptive platform trial. But the pandemic amply demonstrated the potential of the format. Jul 4, 2022 · In oncology drug development, indication selection and optimal dose identification are the primary objectives for the early phase of clinical trials and could significantly impact the probability of success. Thirdly, the aim is to describe CHMP’s position Mar 10, 2021 · Platform trials improve the efficiency of the drug development process through flexible features such as adding and dropping arms as evidence emerges. Platform trials refer to clinical trials that allow new interventions to be added to the platform over time even, if they are not pre-specified in the design stage. Double-Blind Placebo-Controlled Trial Feb 28, 2018 · Adaptive designs can make clinical trials more flexible by utilising results accumulating in the trial to modify the trial’s course in accordance with pre-specified rules. Here, we expand on the PNOC022 rationale and discuss various considerations, including liquid biome, microbiome, and genomic biomarkers, quality-of-life endpoints, and novel imaging modalities, such 20 the key methodological topics unique to platform trials and important design features to guide study 21 planning and protocol development and , thereby, ensure that reliable effect estimates, adequate to 22 support regulatory decision making, can be generated. , multiple treatments or populations or that allow adding/removing arms during the trial), offering enhanced efficiency and a more ethical approach to trial evaluation. 1 The As the therapeutic effect for the SOC is often well documented in historical trials, we propose a Bayesian platform trial design with hybrid control based on the multisource exchangeability modelling (MEM) framework to harness historical control data. Sep 1, 2020 · In this review, we describe key concepts of platform trials with case study discussion of two hallmark platform trials in STAMPEDE and I-SPY2. Master protocols allow major adaptations such as ceasing randomization to an experimental arm or introducing new comparisons through the addition of new experimental arms – see section “ Adding New Research Arms and Comparisons . Late Stage Trial The Platform Trial is a late stage trial, meaning that data derived from the trial, if positive, could be used to support approval of new medication for ALS treatment. (2020) Bayesian cluster hierarchical model for subgroup borrowing in the design and analysis of basket trials with binary endpoints, Stat Methods Med Res: 2020 Sep;29(9):2717-2732. However, few studies have compared APT design against conventional randomized clinical trial (RCT) design from a cost-effectiveness standpoint. The benefits and practical challenges of implementing novel trial designs have been discussed widely in the literature, yet less consideration has been given to the statistical implications of adding arms. Chen N, Lee JJ. Dec 10, 2021 · The design of a platform trial poses scientific, statistical, operational, and regulatory challenges. This trial design allows both (1) the seamless addition of new research comparisons when compelling clinical and scientific research questions emerge, and (2) early stopping of accrual to individual comparisons that do not show sufficient activity without affecting Aug 31, 2022 · The design of platform trials can be highly variable. Despite the many advantages of these Dec 5, 2022 · The goal is not to hinder activities that aim to provide patients with an innovative therapeutic solution. In addition, the choice of a study design will depend on the disease area, the competitive landscape, the established industry practices, and the development phase, in particular if the study is exploratory or confirmatory. May 29, 2019 · There are limited research and literature on the trial management challenges encountered in running adaptive platform trials. Bayesian cluster hierarchical model for subgroup borrowing in the design and analysis of basket trials with binary endpoints. 4 This figure template "Platform Clinical Trial Design" is assembled using dynamic BioRender assets (icons, lines, shapes and/or text) and is fully editable. Table 1. Master protocols, e. The HEALEY ALS Platform Trial is testing multiple investigational products in parallel and sequentially in persons with ALS with the goal of rapidly identifying novel treatments to slow disease progression. 3. Examples include scenarios in which there is a desir … Background: A "platform trial" is a clinical trial with a single master protocol in which multiple treatments are evaluated simultaneously. edu. These are trials for simultaneous testing of multiple treatment strategies in separate groups, with plans to discontinue any group that is definitively inferior at planned interim analyses. Compared to a more traditional intervention focussed trial design (is this drug better than usual care / placebo?), a In the era of targeted therapies and immunotherapies, the traditional drug development paradigm of testing one drug at a time in one indication has become increasingly inefficient. Moreover, regulatory authorities appear to be increasingly amenable to platform trial designs. 9 = 64. 7%) and the United Kingdom (n=31, 31. A platform trial is a clinical trial with one single master protocol in which multiple treatments are evaluated simultaneously [11]. Motivated by the Next Generation Personalized Neuroblastoma Therapy (NEPENTHE) trial (Mosse, 2018) for children with relapsed or primary refractory high-risk neuroblastoma, Mu et al. A platform trial design for preventive vaccines against Marburg virus and other emerging infectious disease threats Sep 30, 2016 · Recent success of immunotherapy and other targeted therapies in cancer treatment has led to an unprecedented surge in the number of novel therapeutic agents that need to be evaluated in clinical trials. In the era of targeted therapies and immunotherapies, the traditional drug development paradigm of testing Dec 6, 2023 · The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a multifactorial Bayesian adaptive platform trial that aims to improve the way that S. The platform trial design enables introduction of new interventions … Nominations of therapies for inclusion in the platform trial will continue on an ongoing, rolling basis. Clinical trial design in breast cancer research has been revolutionized, moving towards more efficient and targeted strategies. The investigators for the RECOVERY trial have so far identified four therapies that reduce mortality in patients hospitalised with COVID-19, and have shown that another six therapies are ineffective. The discovery that dexamethasone decreased deaths in severely ill patients Researchers, clinicians, policymakers and patients are increasingly interested in questions about therapeutic interventions that are difficult or costly to answer with traditional, free-standing, parallel-group randomized controlled trials (RCTs). For example, certain trials incorporate Bayesian algorithms that permit adaptative decisions, such as expanding or deleting study arms while the trial is running [ 71 ]. Paganoni discussed the origin of the platform trial research design and reviewed Platform Trial progress to date. … May 13, 2020 · In this article, we describe the development and implementation of a new clinical trial design OPTIM-ARTS (Open Platform Trial Investigating Multiple Compounds—Adaptive Randomized Design with Treatment Selection)—with application to a phase II study of an anti-PD-1 antibody in combination with other novel targeted therapies and immuno May 12, 2022 · Motivated by a real-world application, we propose a master-protocol–based Bayesian platform trial design with mixed endpoints (PDME) to simultaneously evaluate multiple drugs in multiple indications, where different subsets of efficacy measures (eg, objective response and landmark progression-free survival) may be used by different Oct 22, 2020 · To address these issues, we propose a Bayesian phase I/II platform trial design, which accounts for the unique features of immunotherapy, thereby allowing investigators to continuously screen a large number of immunotherapeutic treatments in an efficient and seamless manner. A basket trial is when one therapy is tested on more than one disease or subtype of disease, and an umbrella trial is where multiple therapies are tested platform trial design for stroke patients Guangyi Gao1*, Byron J. 3–36. While they are most often conducted as randomised clinical trials with adaptive trial designs (adaptive Sep 6, 2022 · Methods: To address these needs, we present a Bayesian platform trial design based on a beta-binomial model for binary outcomes that uses three key strategies: (1) hierarchical modeling of subgroups within treatment arms that allows for borrowing of information across subgroups, (2) utilization of response-adaptive randomization (RAR) schemes Three types of master protocols are basket, umbrella, and platform trials. Aug 3, 2023 · Furthermore, the adaptive platform trial design of RECOVERY allowed enrolment in less effective arms to be stopped, meaning fewer patients were treated suboptimally and increasing the number of Fig 1. May 1, 2023 · Because of the innovative design features employed in these trials, adaptive platform trials introduce a number of challenges for trial design, analysis, and interpretation. The objective of this review is to summarize published platform trials, examine specific methodological design features among these studies, and hopefully aid readers in the evaluation and interpretation of platform trial results. May 7, 2022 · plasmaMATCH trial design and clinical results. harvard. Larger upfront investment in terms of time and money may be required for an adaptive platform trial, but, over the long term, provide a foundation for more efficient collaboration, discovery, and improvements in care . Types of Master Protocols. Unlike traditional designs, MAMS allows researchers to test multiple treatment arms at the same time, with the ability to drop treatments that don’t show promise and add new ones as they Feb 19, 2024 · The shift towards adaptive platform trials. The median sample size was 892 (IQR: 1835–255 = 1580), and the median study duration was 58. The platform trial design enables introduction of new interventions after the trial is initiated to evaluate multiple interventions in an ongoing manner using a single overarching protocol called a master (or core) protocol. arm, multi-drug trials (Particularly for basket trials) • What is the planned pooling strategy? Need for pre-specification (cherry picking must be avoided) • If a ‘vast majority’ of the sub-trials corresponding to the different target populations are positive, can a global indication be obtained and how? (this will depend on the unit In this section, we introduce several platform designs with the survival endpoints. Study design and setting: In this review, we describe key concepts of platform trials with case study discussion of New investigational products are added to the HEALEY ALS Platform Trial, supported by pharma, foundation partners, philanthropy, federal and other fundraising initiatives. Aug 28, 2019 · In response, researchers have proposed new RCT designs such as adaptive platform trials (APTs), which are able to study multiple interventions in a disease or condition in a perpetual Sep 18, 2019 · Background Master protocols, classified as basket trials, umbrella trials, and platform trials, are novel designs that investigate multiple hypotheses through concurrent sub-studies (e. Despite the presence of ethical, logistical, and data complexities, it is anticipated that ongoing technological and regulatory enhancements will pave the way for even more refined research approaches, subsequently influencing future research, clinical Adaptive platforms allow for the evaluation of multiple interventions at a lower cost and have been growing in popularity, especially during the COVID-19 pandemic. . This work proposes a master‐protocol–based Bayesian platform trial design with mixed endpoints (PDME) to simultaneously evaluate multiple drugs in multiple indications, where different subsets of efficacy measures may be used by different indications as single or multiple endpoints. 9 (IQR: 101. Background. Despite a clear uptake on the advantages in the concepts and designs, master protocols are still yet to be widely used. Methods A Jan 4, 2022 · Platform trials are a type of randomized clinical trial that allow simultaneous comparison of multiple intervention groups against a single control group that serves as a common control based on a prespecified interim analysis plan. proposed a Bayesian phase I/II platform trial design, which Feb 17, 2016 · A “platform trial” is a clinical trial with a single master protocol in which multiple treatments are evaluated simultaneously. Apr 22, 2022 · Furthermore, a MAMS design can be part of trials with master protocols such as platform or umbrella trials. The included platform trials primarily recruited or plan to recruit patients from North America or Europe, with most subjects being recruited from the United States (n=39, 39. Motivated by competing drug therapies for lymphoma, we prop … Objectives: The objective of the study was to outline key considerations for general clinical readers when critically evaluating publications on platform trials and for researchers when designing these types of clinical trials. Nov 27, 2023 · Adaptive platform trials (APTs) have become increasingly popular in recent years in infectious diseases research. Examples of trials using master protocols Industry partners from the companies noted below are working closely with the Healey Center Trial Design Team, the Northeast ALS Consortium (NEALS), Barrow Neurological Institute and Berry Consultants to tailor the arm of the HEALEY ALS Platform Trial to their experimental study drugs. Mar 4, 2021 · Background In recent years, the popularity of multi-arm multi-stage, seamless adaptive, and platform trials has increased. Jun 6, 2022 · The Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis (ISPY COVID-19 trial) was designed and implemented in early 2020 to evaluate investigational agents rapidly and simultaneously on a phase 2 adaptive platform. Results: We identified 58 COVID-19 platform trials globally registered between January 2020 and May 2021. Motivated by a real-world application, we propose a master-protocol-based Bayesian platform trial design with mixed end … Mar 20, 2024 · All authors worked in teams of 2 from trial protocols (master and subprotocols), result publications, trial registries, and the official trial websites into a REDCap data sheet. Industry and academic investigators interested in adding their treatment ideas to the HEALEY ALS Platform Trial or working with the Healey & AMG Center ALS Trial Design Team should contact HealeyCenterforALS@mgh. This manuscript outlines the design, rationale, implementation and challenges Mar 4, 2021 · In terms of platform trials, two programs stand out: (1) An implementation of a Bayesian drug combination platform trial design with adaptive shrinkage and (2) an implementation of a Bayesian platform design using adaptive randomization with early futility and/or efficacy stopping, which allows multiple arms with or without a control group The development and implementation of a new clinical trial design OPTIM-ARTS (Open Platform Trial Investigating Multiple Compounds—Adaptive Randomized Design with Treatment Selection)—with application to a phase II study of an anti-PD-1 antibody in combination with other novel targeted therapies and immuno-agents in metastatic melanoma is The parent protocol recommended design, primary analysis, and key sensitivity analyses were developed through early and frequent communication between trial investigators and the FDA to ensure that results from the HEALEY ALS Platform Trial would generate evidence supportive of regulatory review of novel agents if positive results are obtained. Regimen-specific appendices specify the uniquely tailored designs used to evaluate each investigational product. About 50% of trials publicly share their protocol, and 31 trials (53%) intend to share trial data. Watch recording | Download slides (PDF) May 18, 2023: Weekly Q&A Jan 30, 2021 · To address these issues, we propose a Bayesian phase I/II platform trial design, which accounts for the unique features of immunotherapy, thereby allowing investigators to continuously screen a large number of immunotherapeutic treatments in an efficient and seamless manner. 29,30 We documented the different labels used in study records (eg, “platform trial,” “trial platform,” “platform study,” “platform design,” or Sep 6, 2022 · To address these needs, we present a Bayesian platform trial design based on a beta-binomial model for binary outcomes that uses three key strategies: (1) hierarchical modeling of subgroups within treatment arms that allows for borrowing of information across subgroups, (2) utilization of response-adaptive randomization (RAR) schemes that seek Apr 11, 2024 · Sabrina Paganoni, MD, PhD of Massachusetts General Hospital presented updates on the HEALEY ALS Platform Trial and answered questions from the audience. Aug 1, 2023 · This narrative review provides a summary of the main lessons drawn from EU-PEARL to facilitate broader adoption of platform trials by supporting drug developers, patients and their communities, investigators and regulators involved in planning and design of platform trial. [2] Aug 28, 2019 · In response, researchers have proposed new RCT designs such as adaptive platform trials (APTs), which are able to study multiple interventions in a disease or condition in a perpetual Mar 8, 2023 · The objective of this review is to summarize published platform trials, examine specific methodological design features among these studies, and hopefully aid readers in the evaluation and interpretation of platform trial results. A further development from the so-called “seamless” designs is that which comes under the broad description of “platform trials” or “master protocols. ” We focus here on adaptive Oct 24, 2019 · Because most cancer trial designs have been developed for cytotoxic agents, we will discuss how these time-tested design principles hold relevance for targeted cancer therapies, and we will delineate how a master protocol may serve as an efficient platform for safety and efficacy evaluations of novel targeted therapies. Sketch is the all-in-one platform for digital design — with collaborative design tools, prototyping and developer handoff. To customize your own personalized figure using this template as a starting point, click "Use Template". The UK-based plasmaMATCH trial [] [ISRCTN16945804, NCT03182634, CRUK/15/010] (Fig. However, many design-related questions and questions regarding which operating characteristics should be evaluated to determine the potential performance of a specific trial design remain and are often further complicated by the complexity of such trial designs. May 28, 2023 · Platform trials allow efficient evaluation of multiple interventions for a specific disease. Bayesian methods design of such trials, with a variety of terms such as umbrella, basket, or platform describing specific designs (Woodcock and LaVange 2017). Stopping or decision rules must be carefully prespecified, and there remain issues in evaluating the rigor and appropriateness of these key platform design decisions. To watch a short video explaining the HEALEY ALS Platform Trial design, click here. Feb 8, 2023 · Platform trials long predate the emergence of COVID-19. During the Coronavirus disease 2019 (COVID-19) pandemic, there has been a clear movement towards new platform and adaptive trial design models that have helped to accelerate the research process and the identification of effective countermeasures for pandemic control 1. 3 Trial learning can occur perpetually as interventions are cycled in and out as conclusive evidence is Jul 21, 2020 · In a platform trial, patients with a single disease are randomly assigned to a group of different therapies on the basis of a decision algorithm to determine whether any therapy has benefit. In the right part of this figure, it is the 2+2-experimental arm trial. The RECOVERY adaptive platform trial in the United Kingdom demonstrated the substantial value Nov 6, 2020 · The INHIBIT Clinical Trials Platform is innovative because it uses a Bayesian platform design to compare novel agents in 2 linked randomized phase 3 trials, the Inhibitor Prevention Trial and the Inhibitor Eradication Trial, and it allows for the conduct of these studies in the rare disease hemophilia, for which classical trial design is not Jun 23, 2021 · Master protocol, categorized as basket trial, umbrella trial or platform trial, is an innovative clinical trial framework that aims to expedite clinical drug development, enhance trial efficiency, and eventually bring medicines to patients faster. The Healey ALS Platform Trial is a multicenter, randomized, placebo-controlled, adaptive, perpetual platform trial. According to trial registries, 16 trials have added new therapies (median 3, IQR 4) and 11 have dropped arms (median 3, IQR 2. Saver 3, Caitlyn Meinzer2 and the STEP-STONE Executive Committee Abstract Background: Platform trials are well-known for their ability to investigate multiple arms on heterogeneous patient trial design called the platform trial has recently been proposed, which could be used to greatly accelerate the efficiency of clinical trials. Jan 10, 2021 · As well as single study designs, Bayesian adaptive methods are being employed to build “platform” designs (Adaptive Platform Trials). Researchers, clinicians, policymakers and patients are increasingly interested in questions about therapeutic interventions that are difficult Jun 23, 2021 · Non-profit organization sponsored platform trials, on the other hand, may design Phase II/III trials with market registration intentions as they usually collaborate with various companies while designing such a trial so internal portfolio prioritization would not be a concern. Platform trials are perhaps the closest to model to how care is delivered at the individual patient level. This week, Dr. 2 The I-SPY COVID-19 Trial is a phase 2, multicentre, multiarm, adaptive, open-label, randomised controlled Nov 29, 2023 · Innovative Design. The Multi-Arm Multi-Stage (MAMS) trial design is a flexible and adaptive approach that has improved the speed and efficiency of clinical trials worldwide. 1 Adaptive Phase I/II Platform Design for the Immunotherapy Drugs. Platform trials, also referred to as multi-arm The I-SPY COVID-19 Trial was inspired in large part by the I-SPY 2 Trial, a phase 2 adaptive platform clinical trial designed to discover novel treatments for patients with early-stage breast cancer with high risk for early recurrence. 随着肿瘤精准治疗的不断发展,新的靶向治疗药物层出不穷,急需提高临床研究的效率。也是在这样的背景下出现了创新的伞式研究(Umbrella Trials)和篮式研究(Basket Trials)。 伞式研究简单的说就是一个肿瘤疾病… This combination treatment aimed at inducing metabolic distress led to the design of the first DMG-specific platform trial PNOC022 (NCT05009992). Jan 1, 2021 · Platform trials. 5). These designs help to further accept additions or exclusions of new therapies or patient populations during the clinical trial. To reduce a clinical trial's cost and ethical risk to its enrollees, some oncology trial designers have suggested borrowing information from similar but already completed trials to reduce the number of patients needed for the current study. Sep 1, 2020 · In this review, we describe key concepts of platform trials with case study discussion of two hallmark platform trials in STAMPEDE and I-SPY2. Academic and industry colleagues are encouraged to engage with the Healey Center ALS Trial Design Team at any time to work together on ALS therapy development. 3%) were registered between 2020-2022, coinciding with the COVID-19 pandemic. In a world first, the SNAP trial will simultaneously investigate the effects of multiple intervention modalities within multiple groups of Jun 7, 2018 · This type of design is also referred to as an umbrella or basket approach, or more broadly, it is referred to as a platform trial, describing an experimental platform for assessment of multiple interventions, where site networks continuously recruit participants to a number of ongoing trials using a master protocol with novel end points and Methods: To address these needs, we present a Bayesian platform trial design based on a beta-binomial model for binary outcomes that uses three key strategies: (1) hierarchical modeling of subgroups within treatment arms that allows for borrowing of information across subgroups, (2) utilization of response-adaptive randomization (RAR) schemes In response, researchers have proposed new RCT designs such as adaptive platform trials (APTs), which are able to study multiple interventions in a disease or condition in a perpetual manner, with interventions entering and leaving the platform on the basis of a predefined decision algorithm. Sep 15, 2020 · Platform trials referred to as Multi-Arm, Multi-Stage (MAMS) design trials evaluate several interventions against a common control group and can be perpetual. Jul 6, 2017 · Potential Design of a Platform Trial Involving a Single Disease. Schema of a two-period 2+2-experimental arm platform trial. P2P capitalizes on PPMI study infrastructure, expertise, and ongoing clinical and biomarker data collection to de-risk industry investments in pioneering therapies for individuals at risk of PD diagnosis. Traditional phase II clinical trial designs were developed for evaluating one candidate treatment … Mar 4, 2021 · Background: In recent years, the popularity of multi-arm multi-stage, seamless adaptive, and platform trials has increased. Jul 30, 2023 · Conclusions. Left part of the figure shows a traditional three-arm trial, in the context of this paper, we refer it as a 2-experimental arm trial as it has 2 experimental arms and 1 common control. A master protocol may involve direct comparisons of competing therapies or be structured A platform trial is a type of prospective, disease-focused, [1] adaptive, randomized clinical trial (RCT) that compares multiple, simultaneous and possibly differently-timed interventions against a single, constant control group. ” May 12, 2022 · Motivated by a real-world application, we propose a master-protocol–based Bayesian platform trial design with mixed endpoints (PDME) to simultaneously evaluate multiple drugs in multiple indications, where different subsets of efficacy measures (eg, objective response and landmark progression-free survival) may be used by different Feb 28, 2022 · The term “platform” generally implies the use of a master protocol as a foundation to study multiple treatments for 1 disease; for example, specifying the study population, key enrollment features, outcome measures, etc, on top of which multiple interventions can be studied (Figure [A]). aureus bloodstream infection, a globally common and severe infectious disease, is treated. Platform trials can be applied to all phases of clinical trial research. , basket trial, umbrella trial, and platform trial, have become popula … Most platform trials (n=67, 68. g. The Path to Prevention (P2P) platform trial is designed to catalyze clinical development for prodromal PD. [2] Mar 8, 2023 · The objective of this review is to summarize published platform trials, examine specific methodological design features among these studies, and hopefully aid readers in the evaluation and interpretation of platform trial results. ” The idea is that several related trials can all be conducted under one protocol. Sep 18, 2019 · The majority of platform trials were randomized (n = 15/16), and phase III investigation (n = 7/15; one did not report information on phase) was more common in platform trials with four of them using seamless II/III design. A platform trial is a clinical trial in which multiple treatments or diseases are evaluated within the same protocol. Trials with an adaptive design are often more efficient, informative and ethical than trials with a traditional fixed design since they often make better use of resources such as time and money, and might require fewer Jan 10, 2024 · Adaptive platform trials aim to be durable learning research systems (3–5). Get started for free. Our proposed platform trial has much in common with this definition Common features and issues that arise with adaptive platform trials, which can study multiple therapeutic interventions in a disease in a perpetual manner, are reviewed and recommendations to improve the efficiency of drug development are put forward. As previously described in Annals of Neurology, a master protocol specifies the global trial design. Adaptive platform designs offer flexible features such as dropping treatments for futility, declaring one or more treatments superior, or adding new treatments to be tested during the course of a trial. dhzle enhx ufcw kjse qinz dxdybk ydg fkem idicxf xdeqgkxl