Methodology Forum March 4, 2015

March 4, 2015 (2:00-4:00pm EST)

Meeting Contact: wood@hcp.med.harvard.edu

Agenda

2:00 – 2:15 Objectives/Logistics

2:15 – 2:30 Introductions

2:30 – 2:45 Case Study 1: Matthew Brennan (Duke)

2:45 – 3:00 Discussion

3:00 – 3:15 Methods Study: Laura Hatfield (Harvard)

3:15 – 3:30 Discussion

3:30 – 3:45 Next Steps

Summary

  • Forum meetings planned on a quarterly basis
  • Summary of meeting posted on public website
  • Form collaborations
  • What can this group do:
    • Write white papers/participate in public forms
    • Identify common problems and propose solutions
      • Prioritize gaps in key methodological areas
    • 3 problems identified by Dr. Brennan:
      • multiple treatments,
      • missing data,
      • multiple comparisons
    • Dr. Hatfield:
      • Learning curve issues: how handled in post-market setting?
      • Make better use of realistic loss functions (enumerate actions that industry may face, that patients may face, that a regulatory agency may face)

Combining randomized trial data to estimate heterogeneous treatment effects

Authors  Hatfield, Laura; Kramer, Daniel;  Normand, Sharon-Lise
Year Published 2015
Link to white paper

Abstract

Heart failure arises, progresses, and responds to therapy differently in different people. Yet clinical trials often lack power to estimate treatment effects for subgroups, or enforce eligibility criteria that exclude some patients entirely. Combining information across trials increases power for subgroup estimates and expands generalizibility. However, naively pooling patient-level data sacrifices the benefits of randomization, and pooling study-level estimates must consider trial heterogeneity.We develop and illustrate approaches for combining information across trials to estimate effects in men and women with heart failure who are treated with implantable cardioverter-defibrilliator (ICD) alone or in combination with cardiac resynchronization therapy (CRT-D). We consider individual- and trial-level factors that may confound or mediate subgroup treatment effects. For example, ischemic disease is more common in men; could this explain why women appear to benefit more from CRT-D than men?Our Bayesian models estimate sex-specific treatment effects across trials, accounting for uncertainty, confounding, and mediation. We find that with a very small number of heterogeneous studies, hierarchical modeling offers few benefits over conventional effect pooling,producing wider credible intervals but little shrinkage. We also find little evidence for residual confounding within subgroups, but some evidence of interactions between left bundle branch blockage and ischemic etiology in the sex-specific treatment effects, suggesting further study.

Acknowledgments

LAH and SLN are supported by contract DHHS/FDA-223201110172C and grant 1U01FD004493-01 from the Center for Devices and Radiological Health, US Food and Drug Administration.DBK is supported by a Paul B. Beeson Career Development Award (NIA K23AG045963).

Comparative Effectiveness of Robotic-Assisted vs Thoracoscopic Lobectomy.

Journal Journal of Endourology
Authors
Subroto Paul, MD, FCCP; Jessica Jalbert, PhD, MD; Abby J. Isaacs, MS; Nasser K. Altorki, MD, FCCP; O. Wayne Isom, MD; Art Sedrakyan, MD, PhD
Year Published 2014
Link to Publication

BACKGROUND:  Robotic-assisted lobectomy is being offered increasingly to patients. However, little is known about its safety, complication profile, or effectiveness.

METHODS:  Patients undergoing lobectomy in in the United States from 2008 to 2011 were identified in the Nationwide Inpatient Sample. In-hospital mortality, complications, length of stay, and cost for patients undergoing robotic-assisted lobectomy were compared with those for patients undergoing thoracoscopic lobectomy.

RESULTS:  We identified 2,498 robotic-assisted and 37,595 thoracoscopic lobectomies performed from 2008 to 2011. The unadjusted rate for any complication was higher for those undergoing robotic-assisted lobectomy than for those undergoing thoracoscopic lobectomy (50.1% vs 45.2%, P < .05). Specific complications that were higher included cardiovascular complications (23.3% vs 20.0%, P < .05) and iatrogenic bleeding complications (5.0% vs 2.0%, P < .05). The higher risk of iatrogenic bleeding complications persisted in multivariable analyses (adjusted OR, 2.64; 95% CI, 1.58-4.43). Robotic-assisted lobectomy costs significantly more than thoracoscopic lobectomy ($22,582 vs $17,874, P < .05).

CONCLUSIONS:  In this early experience with robotic surgery, robotic-assisted lobectomy was associated with a higher rate of intraoperative injury and bleeding than was thoracoscopic lobectomy, at a significantly higher cost.

Long term survival with thoracoscopic versus open lobectomy: propensity matched comparative analysis using SEER-Medicare database

Journal BMJ
Authors
Subroto Paul,  Abby J Isaacs,  Tom Treasure, Nasser K Altorki, Art Sedrakyan
Year Published 2014
Link to Publication

Abstract

OBJECTIVE:

To compare long term survival after minimally invasive lobectomy and thoracotomy lobectomy.

DESIGN:

Propensity matched analysis.

SETTING:

Surveillance, Epidemiology and End Results (SEER)-Medicare database.

PARTICIPANTS:

All patients with lung cancer from 2007 to 2009 undergoing lobectomy.

MAIN OUTCOME MEASURE:

Influence of less invasive thoracoscopic surgery on overall survival, disease-free survival, and cancer specific survival.

RESULTS:

From 2007 to 2009, 6008 patients undergoing lobectomy were identified (n=4715 (78%) thoracotomy). The median age of the entire cohort was 74 (interquartile range 70-78) years. The median length of follow-up for entire group was 40 months. In a matched analysis of 1195 patients in each treatment category, no statistical differences in three year overall survival, disease-free survival, or cancer specific survival were found between the groups (overall survival: 70.6% v 68.1%, P=0.55; disease-free survival: 86.2% v 85.4%, P=0.46; cancer specific survival: 92% v 89.5%, P=0.05).

CONCLUSION:

This propensity matched analysis showed that patients undergoing thoracoscopic lobectomy had similar overall, cancer specific, and disease-free survival compared with patients undergoing thoracotomy lobectomy. Thoracoscopic techniques do not seem to compromise these measures of outcome after lobectomy.