Sequential Trials Symposium
The Centre for Statistical Methodology and the Tropical Epidemiology Group of the London School of Hygiene and Tropical Medicine (LSHTM) invite you to a half day symposium on sequential trials on the afternoon of 26 September 2018. Presentations will highlight recent research and application of these methods, and speakers include Sue Todd (University of Reading), Dominic Magirr (AstraZeneca), Babak Choodari-Oskooei (MRC Clinical Trials Unit at UCL), and Neal Alexander (LSHTM). Attendance is free but registration is required.
Sequential designs are intended to rapidly assess new interventions, particularly when the outcome is rare, and have arguably been under-used in medical research. For example, sequential trials have been proposed as a way of ‘getting an answer sooner and cheaper’ for neglected tropical diseases. This meeting will concentrate on ‘fully sequential’ trials but group sequential designs will also be addressed. In the former, the data are analysed after each patient’s results become available, and the trial is stopped after a pre-specified objective is reached. Hence, the sample size is not fixed in advance. In the group-sequential approach, the sample size is determined conventionally, but the trial may be stopped at one of a small number of interim analyses.
This symposium will take place at Birkbeck College in central London. We anticipate that this will be of interest to statisticians and others involved in the design or analysis of trials, whether or not they have previous experience of sequential trials.
Experimental design is an often under-appreciated area of statistics, even though leading statisticians have always emphasised its importance. In this case study published in the Royal Statistical Society’s magazine, Significance, TEG’s Richard Hayes describes features in the design and analysis of a key HIV prevention trial in Africa that uses cluster randomisation. Read the full article here.
TEG authored paper: Is home-based HIV testing universally acceptable? Findings from a case-control study nested within the HPTN 071 (PopART) trial
Does doxycycline reduce the risk of postoperative trichiasis following surgery in patients with trachomatous trichiasis?
TEG co-authored paper: Oral doxycycline for the prevention of postoperative trachomatous trichiasis in Ethiopia: a randomised, double-blind, placebo-controlled trial http://authors.elsevier.com/sd/article/S2214109X18301116
Accompanying commentary piece from Emily Gower
Doxy trial – Commentary – E. Gower
TEG’s Professor Immo Kleinschmidt discusses the implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets[i]
Long-lasting insecticidal nets (LLINs) have provided protection against malaria for millions of people in malaria endemic countries for nearly two decades. Standard LLINs shield the person(s) under the net from the blood-seeking female mosquito which is likely to be killed through the insecticidal action of the chemical (known as a pyrethroid) on the net. In recent years there have been widespread reports of insecticide resistance in malaria transmitting Anopheles mosquitoes (vectors). There have been justifiable concerns that the emergence of insecticide resistance could herald a catastrophic rebound in malaria disease burden.
Our study, published in Lancet Infectious Diseases, investigated whether LLINs still provide protection against malaria in the presence of insecticide resistance. The study, which was coordinated by WHO, was conducted in five countries (Benin, Cameroon, India, Kenya, and Sudan). In 279 study locations in these countries we simultaneously assessed insecticide resistance in the local mosquito vector population on the one hand, and the effectiveness of LLINs in protecting against malaria infection and disease on the other. Insecticide resistance was measured in a standardised and controlled way which entails exposing samples of local mosquitoes to the insecticide that is used on LLINs. In all study locations LLINs were made available to local communities in sufficient numbers to provide at least one net for every two persons. Effectiveness of LLINs was assessed by following cohorts of children in each of these locations and comparing malaria infection and disease between children sleeping under nets, with those not using nets. Our main finding was that those sleeping under LLINs were exposed to considerably lower rates of malaria parasite infection and disease than those not using LLINs, even in places with insecticide resistance, i.e. where the insecticide that is used on the net no longer kills all mosquitoes. We did not find a measurable difference in the level of protection provided by nets between places where relatively few mosquitoes survived exposure to insecticide (i.e. few showed resistance to insecticide) and places where large proportions of mosquitoes survived (were resistant). Nevertheless, users of nets, although significantly better protected than non-users, continued to be subjected to malaria infection risk. We therefore conclude that regardless of resistance, people living in malaria endemic areas should continue to use long-lasting insecticidal nets to reduce their risk of infection. However, as nets provide incomplete protection, the development of additional vector control tools should be prioritised to reduce the unacceptably high malaria burden.
Once new generation LLINs with proven superiority to standard LLINs become available, their use should be prioritised in areas of pyrethroid resistance, in accordance with recent WHO guidelines[ii]. In the meantime, the use of standard pyrethroid LLINs should continue to be promoted to save lives until more effective malaria prevention methods are widely available.
[i] Kleinschmidt I, Bradley J, Knox TB, et al. Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: a WHO-coordinated, prospective, international, observational cohort study. Lancet Infect Dis 2018; published online April 9.
[ii] Conditions for deployment of mosquito nets treated with a pyrethroid and piperonyl butoxide. WHO 2017. http://www.who.int/malaria/publications/atoz/use-of-pbo-treated-llins/en/
GSK to fund three Fellowships for scientists from sub-Saharan Africa
Three new Fellowships will be awarded over the next three years thanks to a generous grant from GSK to the MRC Tropical Epidemiology Group (TEG) at LSHTM. The Fellowships will build on the success of an existing capacity strengthening initiative aimed at increasing the number of statisticians and epidemiologists in sub-Saharan Africa. The Fellows will take a one-year Master’s degree in Medical Statistics at LSHTM, followed by a one-year placement at a collaborating institution in Africa, and they will also benefit from ongoing mentorship from a member of the Tropical Epidemiology Group. The fully funded Fellowships include tuition fees, travel and a tax free living allowance ensuring that the Fellows will be able to dedicate themselves entirely to their studies. We look forward to sharing details of the successful recipients in due course.
TEG Fellowship – Applications now open
Applications for our 2018 Postgraduate Training Fellowships in Medical Statistics for African Scientists are now open – please click here for details.
Work With TEG
We’re looking for a part time medical statistician to work on the design and analysis of epidemiological studies on eye health in sub-Saharan Africa and Asia. Further details here.
The Friendship Bench
The Friendship Bench is a programme to train lay health workers to deliver talking therapy to people suffering from mental health problems in Zimbabwe. Here, in an excerpt from a forthcoming documentary by State of Mind, TEG member Vicky Simms discusses its success with one of the lay counsellors and Dr Dixon Chibanda, founder and Principal Investigator of The Friendship Bench.
State of Mind, my next film looking at mental Illness in Zimbabwe is now ready.
It will premier in Harare in January. Here @vickysimms_epi talks about why the Friendship Bench pioneered by the film central character @DixonChibanda has been successful @ZimMediaReview @Wamagaisa pic.twitter.com/ninED0UBPt
— State Of Mind (@Stateofminddoc) December 3, 2017
TEG PhD Student shortlisted for MRC’s Max Perutz science writing prize
TEG PhD student Monica Kuteesa was recently shortlisted for the Max Perutz science writing award, which aims to encourage and recognise outstanding written communication among MRC funded PhD students. Her essay, titled “Alcohol, weed, sex: the high trinity” paints a vivid picture of substance misuse among young people in Kigugu, Uganda, which forms part of her PhD “Epidemiology of alcohol misuse, illicit drug use and their association with HIV among young people aged 15-24 years in fishing communities in Uganda”.
Fully funded PhD studentship available immediately
The post is a fully funded UK PhD studentship, including fees, PhD stipend and all the fieldwork costs in KwaZulu-Natal, South Africa. The PhD will be in developing and conducting a randomised controlled trial of network delivered HIV self-test in linking adolescents and young adults to HIV care and prevention.
The post-holder will be expected to be based in South Africa for the duration of the study. The post will be supervised by Maryam Shahmanesh (AHRI/UCL), Kathy Baisley and Janet Seeley (AHRI/LSHTM).
The post is suitable to anyone with an interest in HIV and we will consider applications from a range of disciplines, including clinical researchers, epidemiologists, social scientists, and clinical trialists. Experience of living and working in Southern Africa is desirable. Applications from South Africans are encouraged.
Expressions of interest should be sent to
Cluster Randomised Trials: Second Edition
The second edition of Cluster Randomised Trials, by TEG’s Richard Hayes and Lawrence Moulton of John Hopkins University is out now.
Sexually Transmitted Infections: Challenges Ahead
“Sexually transmitted infections: challenges ahead”, a commission by Lancet Infectious Diseases, was launched at this year’s STI & HIV World Congress in Rio de Janeiro. The Commission examines five key issues for STI control that are facing major challenges globally. TEG member Suzanna Francis co-authored Part 4: STI case management and control in low-income and middle-income countries”
Guest Lecture – Mycoplasma genitalium: antimicrobial resistance and implications for management
On Wednesday 2nd August at 12.45pm, Dr Catriona Bradshaw will be giving a lecture at London School of Hygiene and Tropical Medicine. Full details can be found here.
Uganda Intensive Course in Epidemiology and Statistics
The MRC Unit in Entebbe will be running their 2-week Intensive Epidemiology and Statistics course from 28th August – 8th September 2017. For further details please see the full advert and application form.
TEG Student wins Dengue Prize
TEG PhD Student John Hudstedt has won the Break Dengue Community Action Prize– a prize which rewards initiatives that combat dengue in an innovative way, whilst integrating dengue vaccines as part of a holistic plan. John’s project “Implementing integrated vector management for dengue control” will first be implemented in the province of Kampong Cham, an area which suffers one of the highest dengue incidence rates in Cambodia. The initiative will be further implemented at the national level, through sustained efforts for governmental collaboration. The project was selected from 67 submissions.
The Friendship Bench – how grandmothers are helping fight depression in Zimbabwe
Al Jazeera report on our collaboration with Dr Dixon Chibanda, founder and Principal Investigator of The Friendship Bench, on how trained lay health workers are helping thousands of people suffering from mental health problems.
TEG Fellowship – Applications now open
Applications for our 2017 Postgraduate Training Fellowship in Medical Statistics for African Scientists are now open – please click here for details
Publication of the month
HIV Self-testing – Questions and Answers
WHO are launching new HIV self-testing and partner notification guidelines for World AIDS Day 2016. In preparation for the launch a short video on HIV self-testing has been produced, watch it here
Inaugural Lecture – Professor Helen Weiss
Professor Weiss recently gave her inaugural lecture “Global Adolescent Health: Reducing Storm and Stress”. Watch it here.
The HIV Self-Testing Africa (STAR) Project’s Research website has now been launched
The STAR project is the largest evaluation of HIV self-testing in Africa to date, the results of which will inform WHO normative guidance, support the establishment of appropriate policy, and encourage new manufacturers to enter the self-test market. The STAR Research website contains information about the STAR team, articles and blogs sharing the latest news from members of the STAR research consortium, details of STAR project and other international HIV events, as well as information on STAR publications and other resources relating to HIV self-testing research.
Comments on Sharing Clinical Trial Data – a Proposal from the International Committee of Medical Journal Editors
Comments from members of the Tropical Epidemiology Group and Collaborators on the ICMJE’s proposals for sharing clinical trial data. Read the full letter here – Response to ICMJE
The Friendship Bench – Tackling Zimbabwe’s Mental Health Crisis
Dr Dixon Chabanda, founder, Principal Investigator and our collaborator on the Friendship Bench, is interviewed by the BBC on using talking therapy to help thousands of people who would otherwise have been left untreated.
Trial of convalescent plasma to treat Ebola shows it is safe but needs more data to determine benefits
Results of the EU funded Ebola-Tx trial, where Ebola patients were treated with plasma from survivors has been published in the New England Journal of Medicine with further information on the design and analysis in Clinical Trials. The trial showed that the treatment was safe to use, however, it did not significantly improve the survival chances of Ebola patients. Tansy Edwards, Peter Smith and Neal Alexander of the Tropical Epidemiology Group worked closely with the lead collaborators at the Institute of Tropical Medicine, Antwerp to design the Ebola_Tx trial and analyse the data.
“Ebola-Tx is the largest controlled trial to be carried out to investigate convalescent plasma from survivors as a therapeutic treatment for Ebola. This study demonstrates that it is possible to rapidly form a Consortium of national and international research partners and to conduct a treatment trial to a high standard in the emergency setting of an Ebola outbreak. The nature of the unprecedented outbreak meant that we had to design a trial that could be adapted to the evolving epidemic and address analytical challenges in the face of many uncertainties” Tansy Edwards
“While it was not possible to conduct a randomised trial in the circumstances of the Ebola epidemic in Guinea, the results of this important study indicate that treatment with convalescent plasma from unselected Ebola survivors is unlikely to markedly improve Ebola survival rates. This treatment was relatively complicated treatment to set up and administer and it is very disappointing that, despite these efforts, there was no significant impact on survival. We cannot exclude the possibility that selecting plasma donors with high levels of antibodies against the Ebola virus might be more effective, and this is a direction for future research” Peter Smith
Unpicking statistics – the stories behind the numbers
For World Statistics Day, Dr Vicky Simms and Dr Andrea Rehman from TEG visited a school in Camden and challenged Year 10 students to answer the question “How can we make the world a better place?” Read about their visit here.
12th AIDSImpact conference, July 2015
Field Trials of Health Interventions: A Toolbox (3rd Edition)
The 3rd Edition of Peter Smith, Dick Morrow and David Ross’ edited book: Field Trials of Health Interventions: A Toolbox is now available to download here. The toolbox is a practical guide covering the design, conduct & analysis of trials in low- and middle-income countries. It has been completely updated and expanded to include chapters on aspects such as questionnaire design, ethics, trial governance and grant applications.