Category: Meta-analysis

Clinical trials are about human dynamics: RCT course in Belfast, May 7-8

As a trialist, the pressure of working on a trial is much bigger than being in a small group educational session. Challenges of implementing a trial are multiple, mainly influenced by the values of outcomes for different people. Whose question is the trial answering? If you’ve ever found yourself puzzled by these issues, you may find some solace in reading my notes from a courseon clinical trials. 


7 instructors and 21 participants – all from Northern Ireland (except 2 Dubliners), 2 medics, three 1-st year PhD students and some professors – talked about clinical trials for two days last week at Queens University Belfast. The aim of the course wasn’t to learn everything, but to think laterally about trials. Professor Clarkecovered the basics of starting trials: formulating a clear research question, deciding on comparisons and placebos and dealing with confounding factors. The 7 main ways of dealing with confounding are:
  1. Matching
  2. Exclusion
  3. Stratified sampling
  4. Standardisation
  5. Multivariate modelling
  6. Randomisation

The pleasures and terrors of trial recruitment were described by Dr Maguire. Everybody struggling with meeting the recruitment targets should read the top 10 tipsfor recruiting into trials at the All-Ireland Hub for Trials Methodology Research website. Trialists should plan for what they’re going to do if things don’t go the way they planned. Recruiters can also become tired and it’s good to think ahead about what would possibly prevent them from recruiting. Even small rewards to recruiters, such as cream eggs, can increase their satisfaction. Satisfaction=Retention. Research networks for General Practitioners can facilitate recruitment.

Dr McAneney introduced us to the role of social networks in clinical trials. We are all connected.  All the users of Facebook can be linked by 3.74 steps. Networks make the trials work or crash. Networks allow diffusion of innovation. Decisions of participants and researchers are influenced by networks.

Prof McAuleyhelped the participants to write the protocol and funding application for their first trial. Publishing a trial protocol sets the bar pretty high for researchers – transparency and accountability are keyIf it’s not possible to publish the protocol in a peer-reviewed journal, then post it online. Every protocol is changed over time and they should be listed on the first page. The CONSORT diagram is an essential part of a protocol. It’s the only slide that’s projected during meetings of grant reviewers.

Dr Shorterand Prof Buntingcontinued with tips for analysing outcomes. The essence of any research is control. Although power calculations for trials seem difficult, they involve only a short sequence of basic steps. Categorical outcomes require more data and more participants than continuous outcomes. Analysis of clinical trials assumes that our participants are all from the same population. The classical assumption of trials analysis was that individual differences do not matter, they were ignored. Another assumption that things are measured perfectly never holds.

Finally, Dr Dunlopfinished the course presentations with ethics and data storage.

Conference of Cochrane Evidence: Useful, Usable & Used #CE3U

My journey with Cochrane started one summer afternoon in 2010, when I interviewed a Tallaghtdoctor (Tallaght is a rough suburb in Dublin, Ireland) about treatments for drinking problems of people who also use other drugs. I emphasized that brief psychosocial interventions were the treatment of choice for patients who don’t use other drugs and that there’s no reason why this should be different for drug users. He asked me whether I was Swedish, because of my accent, and replied by a single question which kept me awake at night and started my career as an addiction investigator: “Does it work?” I decided to celebrate the four years of trying to find an answer to his question at the Cochrane conference in Manchester, UK.
Wednesday 23rd April 2014
This year’s conference of UK and Irish Cochrane contributors’ swapped plenaries and workshops – Wednesday kicked off with two sessions of developmental workshops. The motto of the priority setting workshop was  “Don’t start a journey that you can’t finish”. Pragmatism is a very important part of priority setting. The value of setting priorities in healthcare is the expected gain from reducing the uncertainty. In another words, to reduce the probability that somebody somewhere is getting a wrong treatment.
Figure 1. Bees were the theme of Cochrane conference
The key question of the public health workshop was How to produce good reviews quickly? Growing number of people are interested in doing reviews under the public health group. Most public health studies are non-randomised. Evidence forms just one part of the complex process of public health policy – timeliness is the big factor. The idea of local context permeates all policies – is this relevant to your local area? All of us, as Cochrane reviewers, give shades of grey and they [policy makers] want black& white answers.
The first afternoon plenary started a faithful member of the Cochrane family, Nicky Cullum. She described how easy reviews were in the past. Her talk inspired 12 new tweets in the first 5 minutes of the plenary (#CE3Useful). The beginning of Cochrane nursing group was accompanied by skepticism “Are RCTs possible in nursing?  Is experimentation at odds with caring?” The explosion of nursing trials in the recent years posed new challenges “How on earth do we help non-academic clinicians to have both clinical and academic career?” Trisha Greenhalghconcluded the first with provocative lecture about boringness of Cochrane reviews. She used the example of young doctor Archie Cochrane in a German camp to demonstrate that the art of rhetoric consists of logos, ethos and pathos. Her other work on how innovations rise and how they spread further supported the rhetoric argument. While a logo is the only thing in scholarship rhetoric, factual knowledge can be rarely separated from ethical or social context. By trying to do so, the Cochrane researchers are stripping away the very thing they need to be exploring – how to change the world through science. The methodological fetishism developed in Cochrane collaboration (linked to control, rationalism and accountability) hinders production of more realist and interesting reviews.
Thursday morning plenaries helped the delegates to confer after the gala dinner last night. Rich Rosenfeld, a Professor and Chairman of Otolaryngology, explained how Cochrane reviewers can help policy makers by rapid reviews – Good is ok, perfect we don’t need [for guidelines]. A health economist, Karl Claxton, continued the discussion on when no more evidence is needed. Research takes long time and evidence that we already have can inform allocation of research funds for new projects. However, we should be cautious about judging the usefulness trials with hindsight, it’s wrong because we don’t know the context. Neal Maskery made the audience “lol” with very entertaining and interactive plenary which focused on what we know about how people make decisions. Our brain is so good at patterns recognition – it wants to do it all the time. This phenomenon is called Base rate neglect – a cognitive bias. Biases such as this one hinder innovation and affect our decisions in all areas from buying a car to prescribing medicines. Al Mulley, an expert on shared decision making, finished morning lectures with a story of how every patient brings their own context by using examples from his research on how bothersome is urinary dysfunction.

The special addition to the conference was presence of Students 4 Best Evidence, some of whom won prizes from UK Cochrane centre, including free travel and conference participation. Read more about their winning entries on prostatecancer, dentalhealth, smoking, and long-term illness.

From a personal perspective, starting a Cochrane review took me on a journey which led from a clinical question (from the Tallaght doctor), to policy development, medical education and further research in a very short time. I still don’t know whether counselling works for drink problems in people who also use other drugs, but I’ve learned how to find an answer using the Cochrane methodology.

Do talking treatments help problem drinkers who also use illicit drugs? We’re still guessing – by Sarah Chapman

19 Nov 2012

Do talking treatments help problem drinkers who also use illicit drugs? We’re still guessing

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Alcohol Awareness Week starts today, with the theme ‘It’s time to talk about drinking’, so I thought we’d kick-start the week in this bit of the woodland by doing just that. Alcohol Concern’s Hair of the Dog campaign poster displays facts which may well achieve their aim of prompting conversation on this subject, including the surprising information that around 200,000 people will have turned up to work with a hangover today (and people who work are more likely to drink alcohol than unemployed people).
Talking treatments were the focus for a new Cochrane review, published last week, which looked at different psychosocial interventions to reduce alcohol consumption in people with problem alcohol and drug use. Four studies with 594 people were included, comparing cognitive-behavioural coping skills training with 12-step facilitation, a brief intervention with treatment as usual, motivational interviewing with hepatitis health promotion and brief motivational interviewing with assessment only.
Here’s what they found:
  • The only study finding a significant difference found that people in the control group receiving ‘treatment as usual’ drank less alcohol at three and nine months than those receiving a brief intervention.
  • The evidence is weak, coming from low quality studies
  • Studies differed too much for their results to be combined
I was rather surprised to read a positive result favouring the control group, until I discovered that the only additional intervention for the intervention group was a single one-hour talking session. Otherwise, everyone in the trial received ‘treatment as usual’ which included a barrage of things including drugs, medical and psychiatric follow-up AND, wait for it, psychosocial interventions…
The reviewers, not surprisingly, said that
 no conclusion can be made because of the paucity of the data and the low quality of the retrieved studies.
So targeting drug and alcohol use together may be a logical approach, given the high rate of these problems occuring together, but one that still lacks an evidence base. If you want to talk about drinking this week, check-out the drinkaware website for some facts about alcohol and you could use the MyDrinkaware feature to track or cut down your drinking. I’m off now to grab a glass of water, something I definitely don’t drink enough.

Links:

Klimas J, Field CA, Cullen W, O’Gorman CSM, Glynn LG, Keenan E, Saunders J, Bury G, Dunne C. Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users. Cochrane Database of Systematic Reviews 2012, Issue 11. Art. No.: CD009269. DOI: 10.1002/14651858.CD009269.pub2. Cochrane summary 

Sarah Chapman

My name is Sarah Chapman. I have worked on systematic reviews and other types of research in many areas of health for the past 17 years, for the Cochrane Collaboration and for several UK higher education institutions including the University of Oxford and the Royal College of Nursing Institute. I also have a background in nursing and in the study of the History of Medicine.

Read the full article here

Is it easier to recruit participants in space? Ten years of Cochrane and Mike Clarke in Ireland

Tenth annual Cochrane in Ireland conference“From evidence to clinical guidelines” took place on 24 January 2014 at School of Nursing& Human Sciences, Dublin City University.

The 7-hours programme kicked off with a welcome by Professor John Costello, Executive Dean of the Faculty of Science and Health, Dublin City University, followed by the National Clinical Effectiveness Agenda of Dr Kathleen MacLellan, Director National Clinical Effectiveness Committee, Department of Health, Dublin.

Figure 1 Yellow arrow card
Mike Clarke’s (Professor & Director of MRC Methodology Hub, Queen’s University Belfast) random thoughts about randomised trials covered some of the more unusual things people have studied. There are approximately 25000 new randomised trials every year, leading to around 700 000 trials registered in CENTRAL Cochrane database. From this overwhelming amount of evidence, Dr Clarke cherry-picked the most unusual, controversial and interesting trials. His presentation started by distributing yellow-arrow cards to delegates in anticipation of active engagement (See figure 1).

Figure 2 Votes and Mike Clarke
Dr Clarke’s random thoughts started with sweets as tip boosters and continued through gamgee hats to lipsticks, restaurants and vegetables, organ music, citruses, chocolate and space trials – a truly spectacular collection. We all voted on Clarke’s provoking questions about these trials (shown in figure 2): did sweets increase, decrease or unchanged the size of the tip? Does smiley face make more difference in tips size than a hand-written thank you? How beneficial is doodling while working or phone-calling? Mike encouraged us to relate each of these entertaining questions to bigger dilemmas about trials, for example, who is in charge of interpreting whether an intervention works? Or, do we believe something because it was published? Ending on a positive note, Clarke presented trials that were conducted on astronauts in the international space station. The drop-out rate was 0 because they had nowhere to go?

Help, I’m stuck.

After a brief tea and coffee break, the participants dispersed into three parallel sessions (N=25:12:7). Dr Clarke’s session was most popular. Traditionally, Mike uses the power and knowledge of a group of people at his workshops that might have some problems with their Cochrane reviews, but collectively have the knowledge to solve them. The list of participants’ questions that he wrote on the white board at the session start was left with only 2-3 questions unanswered. The group disciplines were mutually helpful – psychology, general practice, nursing or information science, experienced reviewers and Cochrane’s novices.
Two other sessions happened in parallel with Clarke’s workshop. Drs O’Rourke & O’Toole covered practicalities of generating clinical guidelines for cancer treatment in Ireland. Dr Matthews, HRB Cochrane Fellow and Senior Lecturer, School of Nursing & Human Sciences, Dublin City University, helped delegates with issues around starting Cochrane reviews.

Lunch was in the campus canteen – each delegate got a €10 voucher. The atmosphere in the canteen was conducive to contact making; we sat by long tables surrounded by students.

The afternoon programme included 2 lectures by Susan Smith and Anne Matthews, and a conclusion by Dr Teresa Maguire – Head of the population science and health services research at the Health Research Board in Ireland. Dr Matthews corroborated on her experience of doing a review on morning sicknessand being a Cochrane fellow – it’s for life, not just for the 2-year fellowship. Dr Smith is a Professor of general practice at Royal College of Surgeons in Ireland who has done 9 Cochrane reviews. Her rich experiences from these reviews were especially useful for those interested in multimorbidity.

Cochrane conference in Ireland: Making an impact? (#cochraneevidence)

Another conference’s over. This one is among my favourites because it’s about Cochrane collaboration. It attracted around 70 delegates who came to Queens university in Belfast this year.

Lots of interesting discussions with colleagues, e.g. how do you define an expert? or What’s an ideal composition of an expert panel or a committee? It would seem that senior academics, professors or directors are the right experts, but truth may not be so straightforward. Some of these senior people may be simply too busy or think they know it all. Inclusion of junior staff, post-docs, nurses or systematic review authors on expert panels is better because they lack the weaknesses mentioned earlier. What more, they may be the most hard working group in the academia or research in general. Because of that, hey are likely to be dedicated members of expert panels.

A whole different discussion was going on between the conference delegates on Twitter:

Hearing and talking about my/ fellow reviewers’ experiences of doing SRs made me think about what was special different about my own experience or review:

  • it was my first review
  • I’ve applied a truly systematic approach, which received praise from my quality advisor (see previous blog post)
  • it was real quick
  • I had multiple presentations and non-peer reviewed articles about the review
  • I worked for 2 universities
  • I’ve used EPPI-reviewer software, unlike many of my fellow colleagues
  • I’ve used a lot of support from our health information specialists
  • it was done within a unique Health Research Board of Ireland (HRB) fellowships scheme
  • I couldn’t have done it without a strong support from my co-authors and the Cochrane Drugs and Alcohol review group (CDAG)

So, what impact had this year’s Cochrane in Ireland conference on me? It helped me to regain my research identity again.
…and the sky in Belfast was grey, yet again.
A copy of my cochrane review can be accessed here: