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Improving health by improving trials
Feb 26, 2021 4 tweets 2 min read
While platform trials are clearly more prominent in COVID-19 than they were before the pandemic, many other COVID-19 trials use adaptive features. Some examples to follow. #adaptivedesigns

(1/4) The MATIS trial (NCT04581954) is a multi-arm multi-stage trial with early stopping for lack of benefit which seeks to evaluate treatments to prevent more severe disease. @JMSWason

(2/4)
Feb 26, 2021 6 tweets 5 min read
A number of COVID-19 trials use a platform structure and we will look at a few examples in the later stages of development in this thread. #adaptivedesigns
(1/6) The first treatment to be shown to benefit COVID-19 patients was identified within the ACTT trial. The platform allows to stop the evaluation for benefit and lack thereof as well as adding additional treatments.

nejm.org/doi/full/10.10…

@NIAIDNews
Feb 26, 2021 4 tweets 2 min read
Throughout this week we have made the case that adaptive designs can be useful to improve efficiency and discussed practical challenges. Two recent papers have made the case that trials that are adaptive can be particularly helpful in the of COVID-19. #adaptivedesigns (1/4) Different types of adaptations and their utility for studies of COVID-19 treatments have been reviewed in

tandfonline.com/doi/full/10.10…
(2/4)
Feb 25, 2021 4 tweets 1 min read
The TAIloR trial (ISRCTN: 51069819) was a multi-arm multi-stage clinical trial that investigated the utility of different doses of telmisartan to reduce insulin resistance in HIV-positive individuals. @thomas_jaki (1/n). The trial had one interim analysis during which doses that were deemed insufficiently promising were dropped from the study and in the study two of the initial three doses were dropped at this point. (2/n)
Feb 25, 2021 4 tweets 2 min read
The NOTACS trial (ISRCTN: 14092678) an adaptive, multicentre, parallel group, randomised controlled trial comparing the efficacy, cost-effectiveness and safety of 2 types of oxygen therapy in patients at high risk of post-operative pulmonary complication after cardiac surgery 1/n The trial has an embedded interim sample size re-estimation, which is a type of adaptive trial design. This is joint work by @RoyalPapworth, @MRC_BSU (inc. @SofiaSVillar1, @SarahNDawson) (2/n)
Feb 24, 2021 7 tweets 4 min read
Adaptive designs, and other innovative approaches, provide great benefits but are also more complex to run. In 2019, the Adaptive Designs Working Group started investigating what extra resource Clinical Trials Units (CTUs) might need to support #adaptivedesigns. (1/7) Funded by the @NIHRresearch @UKCTUNetwork CTU Support Fund and led by Newcastle CTU, the “Costing Adaptive Trials (CAT)’ project set about answering this question. Step 1 was a snazzy logo. (2/7) Image
Feb 24, 2021 10 tweets 6 min read
We’re now passing over to @DrGWheeler to walk us through software for adaptive designs!
Sorry, attempt 2 (@JMSWason not too experienced with adding gifs!) In 2020 Michael Grayling @UniofNewcastle & @DrGWheeler @ucl published a review of software for #AdaptiveDesigns in clinical trials.

Lack of available software is a known barrier to using better trial designs in practice. Q: “How bad is this problem?” 1/9
journals.sagepub.com/doi/full/10.11…
Feb 24, 2021 9 tweets 8 min read
The fact that adaptive designs allow prespecified changes to be made to an ongoing trial based on interim results also creates the potential for biases to be introduced at different stages of the trial. #AdaptiveDesigns This brings additional demands for transparency and adequate reporting of adaptive trials so that consumers of research findings can make informed judgements about the validity and trustworthiness of results. #AdaptiveDesigns
Feb 24, 2021 8 tweets 4 min read
PANDA is an open access & multidisciplinary practical educational resource for those who are keen to learn more about adaptive designs. The aim is to help them make baby steps & bridge the existing practical knowledge gap. See demo version here: panda.demo2.epigenesys.org.uk Our target audience includes statisticians, clinicians, proposal developers, trial managers, data managers, health economists, and reviewers of grant applications. See the scope of what is covered by the PANDA toolkit: panda.demo2.epigenesys.org.uk/about_panda