The Rheumatologist
COVID-19 News
  • Connect with us:
  • Facebook
  • Twitter
  • LinkedIn
  • YouTube
  • Feed
  • Home
  • Conditions
    • Rheumatoid Arthritis
    • SLE (Lupus)
    • Crystal Arthritis
      • Gout Resource Center
    • Spondyloarthritis
    • Osteoarthritis
    • Soft Tissue Pain
    • Scleroderma
    • Vasculitis
    • Systemic Inflammatory Syndromes
    • Guidelines
  • Resource Centers
    • Axial Spondyloarthritis Resource Center
    • Gout Resource Center
    • Psoriatic Arthritis Resource Center
    • Rheumatoid Arthritis Resource Center
    • Systemic Lupus Erythematosus Resource Center
  • Drug Updates
    • Biologics & Biosimilars
    • DMARDs & Immunosuppressives
    • Topical Drugs
    • Analgesics
    • Safety
    • Pharma Co. News
  • Professional Topics
    • Ethics
    • Legal
    • Legislation & Advocacy
    • Career Development
      • Certification
      • Education & Training
    • Awards
    • Profiles
    • President’s Perspective
    • Rheuminations
    • Interprofessional Perspective
  • Practice Management
    • Billing/Coding
    • Quality Assurance/Improvement
    • Workforce
    • Facility
    • Patient Perspective
    • Electronic Health Records
    • Apps
    • Information Technology
    • From the College
    • Multimedia
      • Audio
      • Video
  • Resources
    • Issue Archives
    • ACR Convergence
      • Systemic Lupus Erythematosus Resource Center
      • Rheumatoid Arthritis Resource Center
      • Gout Resource Center
      • Abstracts
      • Meeting Reports
      • ACR Convergence Home
    • American College of Rheumatology
    • ACR ExamRheum
    • Research Reviews
    • ACR Journals
      • Arthritis & Rheumatology
      • Arthritis Care & Research
      • ACR Open Rheumatology
    • Rheumatology Image Library
    • Treatment Guidelines
    • Rheumatology Research Foundation
    • Events
  • About Us
    • Mission/Vision
    • Meet the Authors
    • Meet the Editors
    • Contribute to The Rheumatologist
    • Subscription
    • Contact
  • Advertise
  • Search
You are here: Home / Articles / Tips for Designing Studies That Actually Reveal Causal Inference

Tips for Designing Studies That Actually Reveal Causal Inference

May 13, 2021 • By Ruth Jessen Hickman, MD

  • Tweet
  • Email
Print-Friendly Version / Save PDF
kentoh / shutterstock.com

kentoh / shutterstock.com

Dr. Kim also emphasized the importance of clearly defining treatment exposures, so the two comparator groups can be presumed to be identical with respect to their risk of outcomes. This can be trickier than it seems at first. For example, it’s important to consider the concept of positivity, which states that the possibility of receiving a treatment must be greater than zero (this would not be true, for example, in case of a drug contraindication). The interventions themselves must also be well defined in areas of timeline, inclusion and exclusion criteria, and other factors.

You Might Also Like
  • Shortcomings and Promises of Genome-wide Association Studies
  • Studies Suggest Similar Risks for Biologics vs. Conventional Therapies for Rheumatoid Arthritis
  • Can REVEAL Tool Predict Survival in SSc-Related Pulmonary Arterial Hypertension?
Explore This Issue
May 2021
Also By This Author
  • How to Manage, Treat Anemia of Inflammation in Patients with Rheumatic Disease

For people intimidated by some of the details of advanced technical methods in causal inference, Dr. Kim pointed out that not all questions require such methods be employed. “Try to make the study question very simple first,” she advised. “Once you have a very straightforward causal question, start with a simpler method, and you will build up your confidence in applying advanced methods later,” she said.

ad goes here:advert-1
ADVERTISEMENT
SCROLL TO CONTINUE

For those looking to learn more about causal inference, Dr. Kim strongly recommends a free textbook by Miguel A. Hernán, MD, MPH, ScM, DrPH, and James M. Robins, MD, Causal Inference: What If, as a good entry point into the topic.1 These researchers were the first to explicitly propose a “target trial” approach to organizing an observational study, an approach also recommended by Dr. Kim.2

Target Trials

In the second part of the March 4 session, Daniel H. Solomon, MD, MPH, chief of the Section of Clinical Sciences at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, expanded on Dr. Kim’s recommendation to follow a target trial approach when designing rigorous observational studies. Dr. Solomon also serves as principal investigator on the VERITY grant and as editor in chief of Arthritis & Rheumatology.

ad goes here:advert-2
ADVERTISEMENT
SCROLL TO CONTINUE

Dr. Solomon noted that accepted research methodologies can evolve over time. For example, the Bradford Hill causal criteria have fallen out of favor somewhat as the research community has realized their limitations. In contrast, the target trial approach has been gaining momentum in recent years.

“For each observational analysis for causal inference, we can imagine a hypothetical randomized trial that we would likely prefer to conduct. That is the target trial,” says Dr. Solomon.

He noted that clinicians want their decision making to be informed by causal knowledge about comparative effectiveness and comparative safety. Deferring decisions is not really an option because it just maintains the status quo.

ad goes here:advert-3
ADVERTISEMENT
SCROLL TO CONTINUE

“A relevant randomized trial would, in principle, answer each causal question about comparative effectiveness and safety,” he said. “But we often can’t have randomized trials because they are expensive. They are sometimes unethical, depending on the study. They can be impractical, and they often can’t deliver timely answers.”

Although observational analyses cannot provide the highest level of evidence, the target trial approach provides a way to carefully and thoughtfully design observational studies, so they can provide more accurate information to inform clinical practice.

The idea is to explicitly emulate the envisioned randomized trial with observational data. This requires rigorous analysis and thorough description of various categories as they would occur in a randomized trial: eligibility criteria, treatment strategies, assignment criteria, assignment procedures, follow-up period, outcome, causal contrast of interest and analysis plan. Problems in any of these areas can lead to results that are difficult to interpret and that cannot help guide wise clinical decisions.

For example, Dr. Solomon described a systematic review he helped perform that analyzed the comparative effectiveness of different rheumatoid arthritis strategies through the lens of a target trial emulation framework.3 Such work might be very insightful, as randomized, controlled trials have been slow to fill this hole in the literature. But 29 out of the 31 trials included in their analysis had one or more design flaws, as determined by a target trial emulation approach, limiting their applicability.

Dr. Solomon sees target trial emulation as a way to strengthen causal inference and thus the strength of our confidence in found associations. “Unfortunately, with observational data, people are often a bit sloppy. That results in a lot of vagaries in the literature. We think that target trial emulation is a way of creating some rigor around how one does these comparative effectiveness studies to bring us closer to causation.”

The March 11 sessions further explored mediation analysis, a highly pertinent concept for interpreting and designing both observational and randomized trials.

Pages: 1 2 3 4 | Single Page

Filed Under: Research Reviews Tagged With: Cause, study design, trialsIssue: May 2021

You Might Also Like:
  • Shortcomings and Promises of Genome-wide Association Studies
  • Studies Suggest Similar Risks for Biologics vs. Conventional Therapies for Rheumatoid Arthritis
  • Can REVEAL Tool Predict Survival in SSc-Related Pulmonary Arterial Hypertension?
  • eConsult Communications Reveal the Common Questions from Primary Care Physicians about Rheumatology Care

About Ruth Jessen Hickman, MD

Ruth Jessen Hickman, MD, was born and raised in eastern Kentucky, where she first cultivated her love of literature, writing and personal narratives. She attended Kenyon college, where she received a Bachelor of Arts in philosophy, summa cum laude. She worked with individuals with psychiatric conditions and later in a neuroscience lab at the University of Illinois, Chicago, before graduating from Indiana University Medical School in 2011. Instead of pursuing clinical medicine, Ruth opted to build on her strength of clearly explaining medical topics though a career as a freelance medical writer, writing both for lay people and for health professionals. She writes across the biomedical sciences, but holds strong interests in rheumatology, neurology, autoimmune diseases, genetics, and the intersection of broader social, cultural and emotional contexts with biomedical topics. Ruth now lives in Bloomington, Ind., with her husband, son and cat. She can be contacted via her website at ruthjessenhickman.com.

View more by this author»

Simple Tasks

Learn more about the ACR’s public awareness campaign and how you can get involved. Help increase visibility of rheumatic diseases and decrease the number of people left untreated.

Visit the Simple Tasks site »

American College of Rheumatology

Visit the official website for the American College of Rheumatology.

Visit the ACR »

Rheumatology Research Foundation

The Foundation is the largest private funding source for rheumatology research and training in the U.S.

Learn more »

The Rheumatologist newsmagazine reports on issues and trends in the management and treatment of rheumatic diseases. The Rheumatologist reaches 11,500 rheumatologists, internists, orthopedic surgeons, nurse practitioners, physician assistants, nurses, and other healthcare professionals who practice, research, or teach in the field of rheumatology.

About Us / Contact Us / Advertise / Privacy Policy / Terms of Use

  • Connect with us:
  • Facebook
  • Twitter
  • LinkedIn
  • YouTube
  • Feed

Copyright © 2006–2022 American College of Rheumatology. All rights reserved.

ISSN 1931-3268 (print)
ISSN 1931-3209 (online)