Results Summary

What was the research about?

Appendicitis occurs when the appendix, a small part of the intestine, gets infected. Without treatment, the appendix can burst, and the infection can spread.

Doctors can treat appendicitis with surgery or antibiotics. In the United States, most doctors treat with surgery to remove the appendix. Studies from Europe show that, for many patients, antibiotics are safe and work well to treat appendicitis.

In this study, the research team wanted to learn if treating patients with antibiotics was as safe and effective as surgery. Patients who received antibiotics took them for 10 days.

What were the results?

The research team assigned half the patients by chance to surgery and half to antibiotics. One month after treatment, general health was no worse for patients assigned to receive antibiotics than it was for those assigned to receive surgery.

Three months after treatment, 29 percent of patients treated with antibiotics went on to receive surgery.

Also, after three months, compared with patients who received surgery, those who received antibiotics:

  • Were more likely to have had a hospital stay right after treatment
  • Were more likely to have had an emergency room (ER) visit after treatment
  • Spent slightly more time in the hospital for complications or to have surgery after treatment
  • Missed fewer days of work

Some patients had appendicolith, a hardened deposit within the appendix. For patients treated with antibiotics, those with this condition were more likely to have surgery later compared to patients without the condition. Of the patients with this condition, 41 percent who were treated with antibiotics had surgery within 90 days.

Who was in the study?

The study included 1,552 patients with appendicitis who were receiving care from one of 25 hospitals in 14 states. Of these patients, 60 percent were White, 9 percent were Black, 6 percent were Asian, and 25 percent were another race or multiple races; 47 percent were Hispanic. The average age was 38, and 63 percent were men.

What did the research team do?

The research team assigned patients by chance to receive surgery or antibiotics. At one and three months after treatment, the team called patients to ask about their general health, hospital and ER visits, and the number of days they missed work.

Patients who had appendicitis previously, doctors, policy makers, and health insurers helped design the study.

What were the limits of the study?

About 10 percent of patients didn’t respond to surveys, which may have affected study results. Only 31 percent of patients agreed to be assigned to a treatment by chance. Results may have differed if all patients had agreed to be assigned by chance.

Future research could track patient outcomes longer after treatment with antibiotics or surgery.

How can people use the results?

Patients and their doctors can use the results when considering how to treat appendicitis.

Final Research Report

View this project's final research report.

Engagement Resources

Journal Citations

Article Highlight: At least in the short term, using antibiotics to treat appendicitis worked as well as surgical removal of the appendix for most patients in the CODA trial, as reported in the New England Journal of Medicine. Health outcomes associated with each treatment were similar. More than 70 percent of patients on antibiotics avoided having surgery and missed less time away from work or school in the three months post-treatment. However, nearly 30 percent who received antibiotics ultimately needed surgery. CODA was conducted at 25 sites nationwide and involved a wider range of patients than previous studies, making its results more broadly applicable to typical patients with appendicitis.

Related Journal Citations

Stories and Videos

Media Mentions

Behind The Knife: The Surgery Podcast (October 5, 2020)
In this episode, Principal Investigator David Reed Flum, MD, MPH, and members of his team discuss the early results of the trial. Listen on Apple Podcasts / Spotify

Click here for larger version
(Credit: CODA Study team)

Study Website

CODA Appendicitis Study
University of Washington


PCORI-Funded Study Examining Treatment Options for Appendicitis Yields Useful Early Results
This PCORI-funded study comparing surgery versus antibiotics for uncomplicated appendicitis released early results that physicians and patients can use when weighing treatment options, especially during the coronavirus pandemic.

Peer-Review Summary

Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.

The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments. 

Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:

  • The reviewers noted that to test the effect of appendicolith status on study outcomes the researchers needed to report on the interaction between the status and the treatment group on the outcomes. In response, the researchers explained that they were not looking at the interaction between appendicolith status and treatment group—they were only interested in the outcomes for patients with an appendicolith because these patients are typically excluded from clinical trials on appendicitis treatment.
  • The reviewers questioned the researchers’ approach to their power calculations, which seemed to be focused on differences between treatment groups even though this study was described as a noninferiority comparison. The researchers confirmed that this was a noninferiority study and revised statements in their report to clarify.
  • The reviewers asked about the participants who refused randomization and were assigned to a concurrent observational study where participants could choose surgery or medication to treat their appendicitis. The researchers edited the report to clarify that they used inverse probability weighting in the observational sample to account for baseline differences between treatment groups. In addition, the researchers compared the observational cohort after adjusting for baseline differences to the randomized cohort and found similar results for study outcomes.

Conflict of Interest Disclosures

Project Information

David Reed Flum, MD, MPH
University of Washington
Comparing Outcomes of Drugs and Appendectomy (CODA)

Key Dates

August 2015
November 2022

Study Registration Information


Has Results
Award Type
Health Conditions Health Conditions These are the broad terms we use to categorize our funded research studies; specific diseases or conditions are included within the appropriate larger category. Note: not all of our funded projects focus on a single disease or condition; some touch on multiple diseases or conditions, research methods, or broader health system interventions. Such projects won’t be listed by a primary disease/condition and so won’t appear if you use this filter tool to find them. View Glossary
Populations Populations PCORI is interested in research that seeks to better understand how different clinical and health system options work for different people. These populations are frequently studied in our portfolio or identified as being of interest by our stakeholders. View Glossary
Intervention Strategy Intervention Strategies PCORI funds comparative clinical effectiveness research (CER) studies that compare two or more options or approaches to health care, or that compare different ways of delivering or receiving care. View Glossary
State State The state where the project originates, or where the primary institution or organization is located. View Glossary
Last updated: April 4, 2024