Talk Evidence

Vaccines have been in the news this week - but when you dig into the stories, it turns out that the hype is about phase 1 trials. We're a long way from being sure any of the 150 possible vaccines being developed actually work. In this talk evidence we're talking to a researcher, a regulator, and a manufacturer about the way in covid-19 is upending normal vaccine development, which hurdles they'll have to reach to get onto the market, and how we'll know which one to choose when they are there. This week (1.10) We said that covid would have a knock-on effect on other treatments, and Helen looks at some research into acute coronary syndrome admissions in the UK. (6.53) Peter Doshi, assistant professor of pharmaceutical health services research at the University of Maryland School of Pharmacy and an editor for The BMJ, tells us what to watch out for in the PICO for a vaccine study. (15.20) Marco Cavaleri, head of Biological Health Threats and Vaccines Strategy at the European Medicines Agency, explains what regulators are looking for when thinking about licencing a vaccine - and how covid has made different agencies around the world align their requirements. (22.22) Philip Cruz, UK head of vaccines at GSK, explains how a manufacturer tests their vaccines, and how they use adaptive study design to past regulatory hurdles and provide information for those choosing which vaccine to use. Reading list Lancet paper - COVID-19 pandemic and admission rates for and management of acute coronary syndromes in England https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31356-8/fulltext ONS Data - Deaths registered weekly in England and Wales, provisional: week ending 3 July 2020 https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsregisteredweeklyinenglandandwalesprovisional/latest The BMJ editorial - Vaccines, convalescent plasma, and monoclonal antibodies for covid-19 https://www.bmj.com/content/370/bmj.m2722 WHO report - Draft landscape of COVID-19 candidate vaccines https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines Research Methods & Reporting The Adaptive designs CONSORT Extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design https://www.bmj.com/content/369/bmj.m115

In this week's Talk Evidence we're hearing about how the death rate has dropped below average, disappointment about HIV drugs for covid-19 treatment, a trial to reduce polypharmacy, and why academic promotions matter to everyone else. 1.35 - Carl gives us one of his death updates 3.30 - Helen asks if it’s finally time to be able to do the international comparisons we’ve been waiting for? 16.10 - New research suggests that extreme PPE prevents transmission - but PPE came with a whole range of other viral suppression measures, and they all work together. 21.30 - The Recovery trial has said that  lopinavir-ritonavir isn’t effective against covid - enough for them to stop the arm of that trial. We talk about this and more treatment evidence. 24.00 - Can a digital intervention reduce poly pharmacy? A new trial on bmj.com says no, but we talk about the composite endpoint and the way the trial is powered. 36.25 - Why academic promotion matters to non academics

This week we're looking beyond the press release for dexamethasone, the long awaited review of antibody testing, and how well people are recovering after surviving acute covid-19. (2.36) The preprint for dexamethasone is finally out - considerably after the press release. Carl digs into it to find out how good the news actually is. (8.49) There are a couple of newly published systematic reviews on antibody testing, so we return to our testing guru Jon Deeks - professor of biostatistics at the University of Birmingham to give us an update. (23.52)Covid-19, it became apparent as the pandemic grew, was more than a respiratory disease - there are systemic effects on almost all organs. As people are recovering from the worst ravages of the disease, the long term consequences of those effects are becoming more clear - Lynne Turner-Stokes, professor of rehabilitation medicine at King's College London. Reading list; Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report https://www.medrxiv.org/content/10.1101/2020.06.22.20137273v1 Cochrane review of antibody tests for covid-19 DOI: 10.1002/14651858.CD013652 British society of rehabilitation medicine guidelines for rehab after covid-19. https://www.bsrm.org.uk/downloads/covid-19bsrmissue1-published-27-4-2020.pdf

This week, we’re asking questions about surgisphere data, and how it might have got into such high impact journals, we’re also talking about the protests around the world about structural racism - and how they intersect with the covid pandemic. (1.39) Helen and Carl talk about the data underlying the newly retracted papers on hydroxychloroquine and ace-inhibitors or ARBs and covid. (7.45) Fiona Godlee, the BMJ’s editor in chief, comes onto the pod to talk about retractions, and why they’re often called for, an rarely done. (25.10) We talk about the protests, and Carl gives us his opinion on the risk of covid transmission during them (spoiler; he thinks it’s low) (37.40) Sonia Saxena, professor of primary care at Imperial College London gives her verdict on the Public Health England report into this disproportionate effect of covid on ethnic minorities in the UK, and pushes back against it being a biological instead of a sociological determination. Reading list: Sonia’s analysis into transforming the health system for the UK’s multiethnic population https://www.bmj.com/content/368/bmj.m268  News Analysis - Covid-19: PHE review has failed ethnic minorities, leaders tell BMJ https://www.bmj.com/content/369/bmj.m2264 The PHE report into the disparate risk of covid to ethnic minorities https://www.gov.uk/government/publications/covid-19-review-of-disparities-in-risks-and-outcomes

In this episode of Talk Evidence, we'll be finding out if second waves are inevitable (or even a thing), how the UK's failure to protect it's care homes is symbolic of a neglected part of public life, and why those papers on hydroxychloroquine were retracted. This is Talk Evidence - the podcast for evidence based medicine, where research, guidance and practice are debated and demystified. Helen Macdonald, UK research editor for The BMJ, and Carl Heneghan, professor of EBM at the University of Oxford and editor of BMJ EBM, talk about some of the latest developments in the world of evidence, and what they mean. This week: 2.00 - Helen looking into a second wave - and finds out from Tom Jefferson, an epidemiologist with the Cochrane Collaboration's acute respiratory infections group, that a "wave" might be a misnomer. 12.00 - Mary Daly, professor of sociology and social policy at the University of Oxford, tells us where the UK went wrong with care homes, and what we’d need to do to stop it happening again. 31.20 - Carl and Helen discuss those hydroxy chloroquine papers, now retracted. This was recorded before that happened, but we decided to keep this section in, because they talk about the reasons the papers should be viewed with caution, and the importance of scrutiny of the data. Reading list: The talk from Mary Daly at Green Templeton College. https://www.gtc.ox.ac.uk/news-and-events/event/covid-19-and-care-homes-what-went-wrong-and-why/

That remdesivir study has finally been published - what does it say and is it as independant as claimed. Also, as the world's focus turned to covid, so have researchers - and they've produced over 15000 papers. How can we sift through the flood of research and know what's any good? (2.30) Helen Macdonald talks to Elizabeth Loder about the volume of research we're seeing, and why journals and peer reviewers are struggling to check it all. (8.15) The study on remdesivir has been published - the trial was stopped early, and the primary outcome switched - we talk about how that increases uncertainty over the results, and could actually delay the treatment. (26.50) We hear from a couple fo readers who wanted to correct us about averages, means, medians. Reading list: The US NIH AID study on remdesivir, published 22nd May in the New England Journal of Medicine Research - preliminary report https://www.nejm.org/doi/full/10.1056/NEJMoa2007764 NEJM - looking at the dose duration https://www.nejm.org/doi/full/10.1056/NEJMoa2015301 Editorial - an important first step https://www.nejm.org/doi/full/10.1056/NEJMe2018715

This week we're focussing on what kind of information we need to be able to collect and use as the country transitions out of lockdown - and why local lockdowns may be here for some time. We also hear about the new antibody tests which are available in the UK - are they actually a game changer? (2.00) Helen explains what some new evidence says about hydroxychloroquine (spoiler; don’t take it for covid-19) (6.40) *Non covid alert* - Carl tells us about new research on compressions stockings for thromboprophylaxis, and the importance of doing research on non-pharmacological interventions (10.30) David Nabarro, Special Envoy of WHO Director-General on COVID19, (28.00) Helen goes back to Jon Deeks, professor of biostatistics at Birmingham, to find out more about these “accurate” tests for covid, endorsed by the government this week. Reading list: Clinical efficacy of hydroxychloroquine in patients with covid-19 https://www.bmj.com/content/369/bmj.m1844 Hydroxychloroquine in patients with mainly mild to moderate covid-19 https://www.bmj.com/content/369/bmj.m1849 David Nabarro’s website, with daily briefings https://www.4sd.info/ News Covid-19: Two antibody tests are “highly specific” but vary in sensitivity, evaluations find https://www.bmj.com/content/369/bmj.m2066

Big data is being crunched to help us tackle some of the enormous amount of uncertainty about covid-19, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. In these podcasts, we're going to try to get away from the headlines and talk about what we need to know - to hopefully give you some insight into these issues. This week. (3.10) Calum Semple, professor of outbreak medicine at the University of Liverpool talks about the ISARIC project - predesigned research brought off the shelf and deployed during a pandemic. (14.20) Ben Goldacre, doctor, researcher and director of the EBM datalab at the University of Oxford, joins us to talk about how his team have managed to pull together records from 40% of NHS patients to look for patterns in covid-19 morbidity and mortality. Reading list OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients. https://www.medrxiv.org/content/10.1101/2020.05.06.20092999v1 Features of 16,749 hospitalised UK patients with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol https://www.medrxiv.org/content/10.1101/2020.04.23.20076042v1

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give you some insight into these issues. This week: (1.20) Carl gives us an update on the England and Wales admission data. (3.00) Helen talks about ways in which spread and severity of infection amongst household contacts. (8.20) We talk natural history of covid-19, and Harlan Krumholz, cardiologist at Yale, tells us what we know, and why it's difficult to have a full picture at the moment. (15.10) Helen picks up on a study from Tim Spectre and colleagues using an app to track cases. (20.00) Henry Scowcroft, one of The BMJ's patient editor, who also works for Cancer Research UK, joins us to talk about patients who are taking part in clinical trials, and how this is affecting them. He also touches on the thin patient participation in the design of covid treatment guidelines. (24.10) Carl talks rapidity of publishing, and where researchers should most target their evidence outreach. Reading list: Reducing risks from coronavirus transmission in the home https://www.bmj.com/content/369/bmj.m1728 Rapid implementation of mobile technology for real-time epidemiology of COVID-19 https://science.sciencemag.org/content/sci/early/2020/05/04/science.abc0473.full.pdf The BMJ Public and Patient participation twitter chat https://twitter.com/hashtag/BMJdebate

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give you some insight into these issues. This week: (1.10) Carl gives us an update on the UK's figures, and how deaths outside are now being counted. (2.10) When the pandemic slows down, and normal services resume - what should we start doing first? Helen picks up some evidence on what they might be. (6.05) There's a signal that covid-19 may be causing coagulopathies in some patients, and Helen picks up on a listeners request for more information. (11.22) John Deeks, professor of Biostatistics at the University of Birmingham, is leading a Cochrane initiative into examining the evidence around testing, and rivals Carl's rant when he explains how some research is being done behind a veil of confidentiality. (35.27) When there's a lot of uncertainty, and the stakes are very high, then tempers can flare. Vinay Prasad, hematologist-oncologist in the US, and host of Plenary Sessions podcast, joins us to talk about having a good, respectful, scientific debate.