Category: RCT

How Cochrane Keeps the Addiction Science in Check

Science isn’t infallible. Humans make mistakes even in this highly sophisticated method of understanding the world around us. Thanks God, addiction researchers get a chance to correct their error. If they publish a big error, the publication may be withdrawn. In smaller cases, the publisher issues a correction. It is interesting to see how such a correction has been issued following publication of our Cochrane systematic review of literature which. Probably this helped to keep the addiction science in check. See it for yourself below.

August 2011: “Alcohol-related brief intervention in patients treated for opiate or cocaine dependence: a randomized controlled study”

Before our review included this study, the authors reported the following figures in tables 3 and 7.

November 2011: “Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users: a Cochrane review”

 Our review was published in November 2011 and re-stated the findings of the above study as: higher rates of decreased alcohol use at three months (risk ratio (RR) 0.32; 95% confidence interval (CI) 0.19 to 0.54) and nine months (RR 0.16; 95% CI 0.08 to 0.33) in the treatment as usual group– See more at: http://summaries.cochrane.org/CD009269/ADDICTN_which-talking-therapies-counselling-work-for-drug-users-with-alcohol-problems#sthash.RcVZGdQA.dpuf

August 2013 “Correction: Alcohol-related brief intervention in patients treated for opiate or cocaine dependence: a randomized controlled study”

After the publication of our review, the authors corrected their figures in tables 1 and 5. The care-as-usual treatment for the control group was no longer stronger than the experimental intervention, the “alcohol-related brief intervention.”

 –

A note on causality in science

Because causal relationships are hard to prove (i.e. cause -> effect), majority of scientific publications rely on correlations. An example of a correlation is a relationship between shorter living expectancy and male gender. Men die younger than women. Although there are many plausible explanations, we cannot pinpoint a single cause.  Similarly, if an article gets corrected following a review in a major synthesis of scientific evidence – the Cochrane review – it may be a pure coincidence or it may be a consequence of the review. 

Substance Abuse Treatment, Prevention and Policy is an open-access peer-reviewed online journal that encompasses all aspects of research concerning substance abuse, with a focus on policy issues. Text taken from www.substanceabusepolicy.com

Cochrane Collaboration hosts the largest database of systematic reviews to inform healthcare decisions. Cochrane reviews are the jaguars of medical evidence synthesis. Cochrane is a global independent network of health practitioners, researchers, patient advocates and others, responding to the challenge of making the vast amounts of evidence generated through research useful for informing decisions about health. Cochrane is a not-for-profit organisation with collaborators from over 120 countries working together to produce credible, accessible health information that is free from commercial sponsorship and other conflicts of interest. Text taken from www.cochrane.org

76th Annual Conference of College on Problems of Drug Dependence: Decide to be fearless& fabulous

Not one, but two conferences in Puerto Rico made my trip fantastic. As usual, the NIDA International forum happened for the 15th time on the weekend before the Conference of the College on Problems of Drug Dependence. The lines below offer some insights from these meetings.

Integration of addiction treatment into primary care: the portals of entry

Is abstinence related with good health? Is decreased drug use related with good health?
Tae Woo Park and Richard Saitz asked these questions in a secondary analysis of data from a clinical trial of 589 patients using cocaine or cannabis with very low dependence proportion among the sample (ASSIST score >27). To answer their questions, they used clinical measures of good health, such as, SIP-D, PHQ-9, and EUROQoL. Health outcomes were associated with decreases in illicit drug use in primary. However, abstinence and decreased use may represent very different magnitudes. Self-reports related dysphoria could also play a role in the differences. It takes a long time to make improvement in those consequences? 6 months of follow up observations may not be enough. Patient-preferred outcomes are paramount: do they want to have a score lower than XY on PHQ-9? What outcomes are important for them?
The TOPCARE (www.mytopcare.org) project implemented guidelines for potential opioid misuse (Jan Liebschutz). Her slides blew up half-way through the presentation but she delivered the talk excellently. Nurse care management was a component of the guideline implementation trial. Academic detailing (45min, with opioid prescribing expert) included principles of prescribing brochure and difficult case discussion. Is academic detailing effective? The Cochranesystematic review of literature found small-to-medium variable effects. The preliminary results of the project show that the nurse manager programme is a no brainer.
Rich Saitz commented on the sad state of affairs in the addiction treatment, where only 10% of people with addiction are in treatment. Integrated care is the best thing since the sliced bread, but where’s the evidence? His research showed no added benefit of integrated versus care as usual. Why? Maybe, addiction is not a one thing, but we treat it like one thing. Dr Tai provoked the audience with a question: “Do our patients with addiction have the capability to participate in the treatment planning and referral?” If they seek medical care for their broken leg and we refer them to an addiction specialist, will they go? most likely not.
But it is the same with hypertension. Referral is a process and not a once-off thing. Although they may not follow our advice at the first visit, a rapport built by a skilled professional over a series of discussions can help them get the most appropriate care.

Does the efficacy of medications for addiction decrease over time?

An old saying among doctors states “One should prescribe a new medication quickly before it loses its efficacy”. Elias Klemperer pooled the data from several Cochrane systematic reviews on addiction medicines, such as, NIRT gum, Acamprosate, or Buproprion. Their effectiveness decreased over time. The changes in methodologies might have caused the decline; also the sponsorship of trials, target populations or publication bias.

Write, wrote, written

Primary author is in the driver’s seat, others are passengers. Primary author pulls the train. Dr Adam Carrico(UCSF) asked us “What are you really passionate about?” Find it and use your passion for those themes to drive your writing habit. Decide to be fearless& fabulous. Develop a writing routine. Put together a queue of writing projects and don’t churn out 2 products at the same time, one of them will suffer. Schedule writing retreats with colleagues. Set Timelines for writing grant and programme time for reviews by trusted people, give people a warning that this is what you’re planning to do. The JAMA June 2014 issue offers useful tips on how to write an editorial.

Dr Knudsen reported on the editorial internship of the Journal of Substance Abuse Treatment – JSAT, which started in 2006, with Dr McGovern (current editor) and Knudsen as the 1stfellows. Success rate of the fellowship applications is 2/30-45, prior involvement is appreciated (peer reviewer, submission). The new 2014 fellows are: Drs Madson and Rash. In the one year of the fellowship, the fellows typically review 12-15 manuscripts, some years, as a managing editor of a special issue. The Drug and Alcohol Dependence journal has a similar scheme.

Check out the http://www.cpddblog.com/

Dennis McCarty won the 2014 NIDA International Program Award of Excellence

 June 14, 2014 ― Professor Dennis McCarty, Ph.D., professor in the Department of Public Health and Preventive Medicine at Oregon Health & Sciences University (OHSU), and director of the Substance Abuse Policy Center in the Center for Health Systems Effectiveness, has been awarded by the 2014 National Institute on Drug Abuse (NIDA) International Program.

The award is for Excellent Mentoring. Dr. McCarty mentors clinicians and researchers who test emerging drug abuse treatments in community settings through the Western States Node of the NIDA Clinical Trials Network, which he codirects. He extends his mentoring to state and local policymakers through his role as director of the Substance Abuse Policy Center in the Center for Health Systems Effectiveness, which works to link policy, practice, and research on substance abuse treatment.

Dr. McCarty also is scientific director of the University of Amsterdam Summer Institute on Alcohol, Drugs and Addiction. I met Dennis in Amsterdam in 2011. He lectured for several days on different policy models and evidence based treatments. Two years later, on March 1, 2013, I joined Dennis as a NIDA CTN INVEST Fellow. INVEST is International Visiting Scientists & Technical Exchange Program for drug abuse research. Oregon Health & Sciences University hosted my six months fellowship during which I assessed the use of Screening and Brief Intervention (SBIRT) for alcohol use disorders among patients receiving agonist medication for opioid use disorders. Visit this post to read more about how I got here. I did not think that the summer school would lead to a fellowship in Portland, OR and I’m most grateful that it did.

With Dennis, I have learned about things I thought did not exist. For example, about researchers who enjoy writing. Writing up research projects is a task that many new researchers fear the most. Dennis is a master writer and his craft is contagious; I’ve discovered a need in me, a strong urge to write a lot and in many different formats. Dennis received the award today, at the 19th annual NIDA International Forum in San Juan, Puerto Rico. The 2014 Forum focused on “Building International Collaborative Research on Drug Abuse.”

Four other experts were awarded 2014 NIDA International Awards of Excellence. Mr. O’Keeffe, a professor at Virginia Commonwealth University, was honored for Excellence in International Leadership. The award for Excellence in Collaborative Research went to Dr. Chawarski, Ph.D., Yale School of Medicine, and Dr. Kasinather, Ph.D., Universiti Sains Malaysia. A special award was presented to Dr. Dewey, Ph.D., Virginia Commonwealth University, in recognition of his service to the addiction research community as founder of the Friends of NIDA, and his research on how opioids and marijuana change brain and contribute to tolerance and addiction.

NIDA International Awards of Excellence winners are selected based on contributions to areas essential to the mission of the NIDA International Program: mentoring, international leadership, and collaborative research. Anybody can suggest a nomination to NIDA. Read more at www.drugabuse.gov/international/awards-excellence.

The NIDA International Program connects people across continents to find evidence-based solutions for addiction, and drug-related HIV/AIDS. NIDA is part of the National Institutes of Health – the principal research agency of the U.S. Government and a component of the U.S. Department of Health and Human Services.

Story first released by OHSU Newsroom: http://www.ohsu.edu/xd/about/news_events/news/index.cfm

Three years post doctorate

27 April 2014
Transitions are life changes that allow us to pause, reflect and plan. Here’s a short history of my transition from the pre-doctoral to the post-doctoral stage. Read the full story here.
Hungary 2007. My Hungarian adventurewas a real turning point in my career. I had to commute to work and spent long hours in trams. Bored of watching cars and people, I started to read open-access articles about addiction. When I found something really relevant to my PhD, I felt like a gold miner who just dug his jewel out of piles of dirt. My passion grew stronger with every new paper.
Figure 1. Jano in transition
Ireland 2008. When we arrived to Ireland in late 2008, I had a small EU grant, with a budget of 3000 euros, and an unclear host organization. We survived for almost a year living from my wife’s EVSstipend and seasonal part-time jobs. My PhD and the EU grant took most of my time, leaving only a couple of hours for job-hunting. When I eventually ran out of money, it was late winter and the job market had dried up. Finally, I found an academic job, initially advertised as a PhD in Translational Medicine but my potential boss – Prof Walter Cullen – told me at the interview that I should apply for a p/t job on the same project. That’s how I came to research drinking among methadone patients in primary care at UCD.
Oregon 2013. In July 2011, only two months after receiving PhD, I have attended a summer school on addiction in Amsterdam, Netherlands. Dr McCarty, the school director, lectured about various policy models and evidence-based treatments for several days. Two years later, I did a NIDA fellowship with Dr McCarty at Oregon Health& Sciences University. Read this post about how I got there.

Lessons learned from junior post-doc

1) Write a lot. Like some teenagers, I used to write poems, songs and short stories. Then I stopped for many years. In Oregon, my wife surprised me with a Prompt-based creative writing course for my birthday. She thought it would be good for me and that I would enjoy it. Dr McCartyencouraged me to submit an essay to the Wellcome Trust Science Writing competition and to write a lot. Since then, writing became the core of my work.
2) Learn a lot. If you think of life as a huge learning experience, you welcome trouble as a gift.
3) Keep at it. Perseverance is critical in science. Progress takes years. New knowledge accumulates slowly. And the desired change is uncertain. While I was distributing clean needles to injecting drug users in inner-city Bratislava, Slovakia, I could see the effect of my work immediately. Now I have to wait ages and the change may not come in my life.
I’ve learned many more lessons than just these three, but I’ve learned how to separate the weed from the wheat from the chaff too. I don’t write about the minor lessons.

Future plans for senior post-doc

  • To stay true to myself
  • To reach a position of independence by:
    • conducting a randomized controlled trial
    • supervising work of junior investigators
  • To maintain a happy work-life balance
  • To pass the accumulated knowledge and skills on other:
    • Doctors and helping professions, by helping them become more competent and confident in addiction medicine research
    • Medical students, by helping them discover and master addiction medicine research

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.