Using a journal club to review and reinforce concepts for medical researchers Brian Healy, Amy Shui

Outline Approaches for journal club Live sessions as part of a web based course: Harvard Catalyst Certificate in Applied Biostatistics Student chosen articles: Program in Clinical and Translational Science Participation in journal clubs for specific hospital departments: MGH PICU and Partners MS Center Dropbox with materials for each session Email me (bchealy@partners.org) for access

Background Statistical techniques used within the medical and basic science literature are becoming increasingly complex Readers of medical papers often ignore the statistics section despite valuable information being presented due to complexity of actual approach or language Nearly all medical researchers participate in journal clubs discussing recent articles so it is a easy to adopt format for these students

Harvard Catalyst Certificate in Applied Biostatistics 35 week on-line introduction to biostatistics (n~200) In addition to the main content of the course, every 3-4 weeks we have a journal club discussing a recent article from NEJM or JAMA (n~15) Goals: Review concepts taught recently in class by reading through article Reinforce ideas by seeing them from an alternative framework Some journal clubs introduce a new topic that is an extension of what we cover in class

Format Article and an associated case study with questions sent out to class prior to session Questions focus on scientific question, analyses chosen and special features of paper (missing data, interim analyses, advanced modeling) 15-20 minutes of small group discussion of case study questions 40-45 minutes of full class discussion of case study questions

Review introductory concepts After about 6 weeks of the course, we have a journal club discussing a randomized trial with a dichotomous secondary outcome Article: Nielsen et al. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest. NEJM 2013; 369: 2197-206. Questions from session: How was sample size calculation completed? What analysis was performed? Were the estimate of the effect and hypothesis test consistent?

Reinforce interpretation of interaction terms About halfway through the course, we discuss an article assessing the interaction term in a logistic regression model Article: Le Cook B et al. Trends in Smoking Among Adults With Mental Illness and Association Between Mental Health Treatment and Smoking Cessation. JAMA. 2014;311(2):172-182. Questions from session: What is the interpretation of each main effect and each interaction term? How was the final model chosen? How was missing data handled?

Discussion of advanced clinical trial designs The fourth unit of the program focuses on study design including clinical trials and the associated journal clubs focus on special issues in RCTs One journal club discusses a 2x2 factorial design Article: Tewari KS et al. Improved Survival with Bevacizumab in Advanced Cervical Cancer. N Engl J Med 2014;370:734-43. We discuss estimation of two treatment effects in a single trial as well as interaction between treatments This study also has interim analyses so we discuss stopping rules A second journal club discusses a non-inferiority trial Article: Giugliano RP et al. Edoxaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2013;369:2093-104.

Interpretation of survival analysis Near the end of the course, we introduce Cox proportional hazards models Article: Goldenberg I et al. Survival with Cardiac-Resynchronization Therapy in Mild Heart Failure. N Engl J Med 2014;370:1694-701. In this article, one factor is a strong effect modifier for the treatment of interest Questions from session: How do the Kaplan-Meier curves show effect modification? How did they test for subgroup differences?

Pros/Cons for on-line program Provide a live component to review and reinforce concepts Demonstrates application of concepts presented in the course in the literature Allow introduction of extensions to concepts Wide range of articles in medical literature can fit many potential scenarios Cons Lose flexibility of on-line program Limited participation

Program in Clinical and Translational Sciences A smaller program of students (n~20) using similar on-line course with additional mandatory in person sessions Two hour session biweekly for 4 months with one hour devoted to journal club One student choses articles to present using recent literature I develop case studies associated with article

Phase II trial in cancer A student was a cancer researcher whose research was impacted by a recent publication Finn et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncology 2015;16:25-35 Questions from session: Why do authors use a one-sided alpha level of 0.1? What is the impact of interim analyses on final analysis?

Pros/Cons of student chosen articles Student volunteers can provide perspective regarding the rationale behind the design Can address specific statistical issues facing a student Articles in NEJM/JAMA usually have large sample size so different statistical issues are discussed in student selected articles Cons: Can be challenging to engage a larger group if article is too specific Student volunteers harder to get than I imagined

Department specific journal clubs A former student of Certificate Program from PICU at MGH invited me to attend monthly journal clubs to provide a “biostatistician’s perspective” on articles they were discussing My primary appointment is at the Partners MS Center, and I perform a similar role at the journal club there

Pros/Cons of department journal clubs Attendees of journal club very appreciative Valuable for statistician if this is their area of research Cons: Reasonably large time investment for the statistician Importance of statistician attendance depends on article

Conclusion Journal clubs provide an excellent way to reinforce and review statistical concepts for medical researchers Journal clubs within a formal course provide an opportunity to review and reinforce many concepts within an on-line course Attendance of a biostatistician at hospital department journal clubs can enhance understanding of recent literature for participants