Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice BMJ Open . 2026 Jan 8;16(1):e098309. doi: 10.1136/bmjopen-2024-098309 Search in PMC Search in PubMed View in NLM Catalog Add to search Comparison of Surgery and Medicine on the Impact of Diverticulitis (COSMID) trial: a protocol for a pragmatic randomised study of diverticulitis treatment in the USA Mariam N Hantouli Mariam N Hantouli 1 Surgery, University of Washington, Seattle, Washington, USA Find articles by Mariam N Hantouli 1, ✉ , Robert H Schmicker Robert H Schmicker 2 Biostatistics, University of Washington, Seattle, Washington, USA Find articles by Robert H Schmicker 2 , Janice E Tufte Janice E Tufte 3 Ambassador, PCORI, Washington, District of Columbia, USA Find articles by Janice E Tufte 3 , Fadwa G Ali Fadwa G Ali 4 Surgery, The University of Texas Southwestern Medical Center, Dallas, Texas, USA Find articles by Fadwa G Ali 4 , Robert D Bennett Robert D Bennett 5 Colon & Rectal Surgery, University of South Florida, Tampa, Florida, USA Find articles by Robert D Bennett 5 , Jessica N Cohan Jessica N Cohan 6 Surgery, University of Utah Health, Salt Lake City, Utah, USA Find articles by Jessica N Cohan 6 , Bryan A Comstock Bryan A Comstock 2 Biostatistics, University of Washington, Seattle, Washington, USA Find articles by Bryan A Comstock 2 , Thomas Curran Thomas Curran 7 Surgery, Medical University of South Carolina, Charleston, South Carolina, USA Find articles by Thomas Curran 7 , Giana H Davidson Giana H Davidson 1 Surgery, University of Washington, Seattle, Washington, USA Find articles by Giana H Davidson 1 , Samuel Eisenstein Samuel Eisenstein 8 Surgery, UC San Diego, La Jolla, California, USA Find articles by Samuel Eisenstein 8 , Katherine N Fischkoff Katherine N Fischkoff 9 Surgery, Columbia University Medical Center, New York City, New York, USA Find articles by Katherine N Fischkoff 9 , Fergal J Fleming Fergal J Fleming 10 Colorectal Surgery, University of Rochester Medical Center, Rochester, New York, USA Find articles by Fergal J Fleming 10 , Irena Gribovskaja-Rupp Irena Gribovskaja-Rupp 11 University of Iowa Health Care, Iowa City, Iowa, USA Find articles by Irena Gribovskaja-Rupp 11 , Mehraneh Dorna Jafari Mehraneh Dorna Jafari 12 Surgery, Weill Cornell Medicine, New York City, New York, USA Find articles by Mehraneh Dorna Jafari 12 , Larry G Kessler Larry G Kessler 13 Health Services, University of Washington, Seattle, Washington, USA Find articles by Larry G Kessler 13 , Mukta K Krane Mukta K Krane 1 Surgery, University of Washington, Seattle, Washington, USA Find articles by Mukta K Krane 1 , Sarah O Lawrence Sarah O Lawrence 1 Surgery, University of Washington, Seattle, Washington, USA Find articles by Sarah O Lawrence 1 , James T McCormick James T McCormick 14 Colon & Rectal Surgery, Allegheny Health Network, Pittsburgh, Pennsylvania, USA Find articles by James T McCormick 14 , Stefanos G Millas Stefanos G Millas 15 Surgery, The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, USA Find articles by Stefanos G Millas 15 , Arden M Morris Arden M Morris 16 Stanford University, Stanford, California, USA Find articles by Arden M Morris 16 , Kelsey M Pullar Kelsey M Pullar 1 Surgery, University of Washington, Seattle, Washington, USA Find articles by Kelsey M Pullar 1 , Caroline E Reinke Caroline E Reinke 17 Carolinas Medical Center, Charlotte, North Carolina, USA Find articles by Caroline E Reinke 17 , Julia T Saraidaridis Julia T Saraidaridis 18 Surgery, Lahey Hospital & Medical Center, Burlington, Massachusetts, USA Find articles by Julia T Saraidaridis 18 , Vlad V Simianu Vlad V Simianu 19 Virginia Mason Medical Center, Seattle, Washington, USA Find articles by Vlad V Simianu 19 , Suzanne P Watkins Suzanne P Watkins 1 Surgery, University of Washington, Seattle, Washington, USA Find articles by Suzanne P Watkins 1 , Nicole B White Nicole B White 1 Surgery, University of Washington, Seattle, Washington, USA Find articles by Nicole B White 1 , Elizabeth C Wick Elizabeth C Wick 20 School of Medicine, UCSF, San Francisco, California, USA Find articles by Elizabeth C Wick 20 , Nicole Wieghard Nicole Wieghard 21 Surgery, Virginia Commonwealth University, Richmond, Virginia, USA Find articles by Nicole Wieghard 21 , David R Flum David R Flum 1 Surgery, University of Washington, Seattle, Washington, USA Find articles by David R Flum 1 , Thomas E Read Thomas E Read 22 Gastrointestinal Surgery, University of Florida College of Medicine, Gainesville, Florida, USA Find articles by Thomas E Read 22 ; COSMID Collaborative Author information Article notes Copyright and License information 1 Surgery, University of Washington, Seattle, Washington, USA 2 Biostatistics, University of Washington, Seattle, Washington, USA 3 Ambassador, PCORI, Washington, District of Columbia, USA 4 Surgery, The University of Texas Southwestern Medical Center, Dallas, Texas, USA 5 Colon & Rectal Surgery, University of South Florida, Tampa, Florida, USA 6 Surgery, University of Utah Health, Salt Lake City, Utah, USA 7 Surgery, Medical University of South Carolina, Charleston, South Carolina, USA 8 Surgery, UC San Diego, La Jolla, California, USA 9 Surgery, Columbia University Medical Center, New York City, New York, USA 10 Colorectal Surgery, University of Rochester Medical Center, Rochester, New York, USA 11 University of Iowa Health Care, Iowa City, Iowa, USA 12 Surgery, Weill Cornell Medicine, New York City, New York, USA 13 Health Services, University of Washington, Seattle, Washington, USA 14 Colon & Rectal Surgery, Allegheny Health Network, Pittsburgh, Pennsylvania, USA 15 Surgery, The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, USA 16 Stanford University, Stanford, California, USA 17 Carolinas Medical Center, Charlotte, North Carolina, USA 18 Surgery, Lahey Hospital & Medical Center, Burlington, Massachusetts, USA 19 Virginia Mason Medical Center, Seattle, Washington, USA 20 School of Medicine, UCSF, San Francisco, California, USA 21 Surgery, Virginia Commonwealth University, Richmond, Virginia, USA 22 Gastrointestinal Surgery, University of Florida College of Medicine, Gainesville, Florida, USA ✉ Dr Mariam N Hantouli; [email protected] None declared. Received 2024 Dec 20; Accepted 2025 Nov 25; Collection date 2026. Copyright © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/ . PMC Copyright notice PMCID: PMC13059936 PMID: 41506759 Abstract Introduction Each year, millions of people experience recurrent diverticulitis episodes. Elective sigmoid colon resection reduces the risk of recurrence, but The American Society of Colon and Rectal Surgeons recommends individualising surgical decisions based on the impact of the condition on a patient’s quality of life (QoL). However, no threshold for QoL impairment has been established to guide decision-making, and evidence comparing elective colectomy with medical management in terms of QoL limitation is limited. To address these gaps and to guide treatment decision-making, we designed the Comparison of Surgery and Medicine on the Impact of Diverticulitis (COSMID) trial. The COSMID trial is a large, pragmatic randomised trial including patients with QoL-limiting diverticulitis that aims to determine if partial colectomy is superior to medical management and explore subgroups that are more likely to respond to each treatment. Methods and analysis COSMID will recruit 250 English-speaking and Spanish-speaking adults with imaging-confirmed and QoL-limiting diverticulitis (defined using a modified diverticulitis-related QoL survey). Participants are randomly assigned to undergo elective partial colectomy or receive comprehensive medical management (eg, selected from options including fibre, probiotics, mesalamine and rifaximin). A total of 100 patients who decline randomisation but consent to follow-up will be included in a parallel observational cohort. The primary outcome is the time-averaged score of the Gastrointestinal Quality of Life Index at 6, 9 and 12 months after randomisation. Secondary outcomes include clinical adverse events, healthcare utilisation, recurrent episodes of diverticulitis and additional patient-reported outcomes like the Diverticulitis Quality of Life instrument, decisional regret and work productivity. Exploratory analyses aim to identify differential treatment effects based on patients’ characteristics. Ethics and dissemination This trial was approved by the Vanderbilt Institutional Review Board (IRB) on 26 August 2019 (IRB #191217). Vanderbilt serves as the institutional review board of record for the following study sites: Albany Medical College, Allegheny Health, Atrium Health Carolinas Medical Center, Virginia Mason Medical Center, Boston University Medical Center, Cedars-Sinai Medical Center, UT Health Lyndon B. Johnson Hospital, Medical University of South Carolina, New York-Presbyterian Queens, Stanford University, University of Pennsylvania, University of California San Diego, University of California San Francisco, University of Colorado Denver, University of Florida, University of Iowa, University of Utah, University of Washington Medical Center, University of South Florida, University of Rochester Medical Center, University of Texas Southwestern Medical Center, Virginia Commonwealth University, Lahey Hospital & Medical Center, Weill Cornell Medical Center and Northwell Health. Rush University Medical Center (approved 8 January 2020), Columbia University Medical Center (approved 28 January 2020), Northwestern University (approved 19 March 2020), Mount Carmel Health System (approved 5 May 2020) and Memorial Health University Medical Center (approved 4 April 2022) are regulated and were approved by their respective IRBs. Results from this trial will be presented at international conferences and published in peer-reviewed journals. Trial registration number NCT04095663 . Keywords: Colorectal surgery, Adult gastroenterology, Patient Reported Outcome Measures, Patient-Centered Care, Randomized Controlled Trial STRENGTHS AND LIMITATIONS OF THIS STUDY. This is a patient-level randomised superiority trial comparing the impact of diverticulitis treatment options, elective colectomy and medical management on clinical outcomes and patient-reported outcomes that matter most to patients. A parallel observational cohort includes patients who decline randomisation, allowing assessment of potential selection bias. The pragmatic trial design incorporates heterogeneity in patient populations, practice settings and clinical care delivery in the USA. Some patient subgroups may underenrol and therefore be underpowered for evaluating effectiveness. The patient-centred trial design integrates input from a diverse group of interest holders in its planning, design and implementation phases. Introduction Diverticulitis continues to be a significant burden on healthcare systems worldwide. In the US alone, 2–4 million patients experience index or recurrent episodes of diverticulitis annually, 1 , 4 and it was estimated that diverticulitis accounted for 208 015 hospital admissions at an aggregate cost of US$2.1 billion in 2014. 2 Most episodes are acute uncomplicated diverticulitis (AUD), defined as intermittent left-sided abdominal pain without associated abscess, bleeding or fistula. AUD usually resolves with medical management. 5 , 7 In the past, elective colectomy was recommended for patients with acute diverticulitis based on the number of acute diverticulitis episodes and their age, with the goal of avoiding more severe episodes as well as the risk of colostomy. 8 However, only a small proportion of patients undergoing non-operative management (~5%) develop more complicated disease, 9 and almost all patients who require emergency surgery and colostomy do so during their first episode of diverticulitis. 10 Moreover, level 1 evidence suggests that medical management options, including probiotics, 11 aminosalicylic acid and rifaximin, 11 can improve diverticulitis symptoms. Given these data, the American Society of Colon and Rectal Surgeons revised their guidelines in 2014, recommending that surgical decisions be individualised based on the impact of diverticulitis on the patient’s quality of life (QoL). 12 13 Yet, there remains no established standard measure of QoL limitation nor a clear threshold for QoL impairment to guide treatment decisions between surgical and medical management. There has also been limited information directly comparing the effectiveness of elective colectomy and medical management for QoL-limiting diverticulitis. This has resulted in two evidence gaps: What is the comparative effectiveness of elective colectomy versus medical management for patients with a history of diverticulitis and related QoL impairment? Is there a threshold measure of QoL impairment that determines which treatment is more effective? The only other comparative trial of these two treatments was the Dutch Diverticular Disease Collaborative Study Group’s DIRECT randomised trial. Though stopped before reaching its planned sample size, the DIRECT trial found that elective colectomy was superior to non-operative management based on a measure of gastrointestinal QoL. 14 There were several features of the DIRECT trial that have resulted in limited uptake in the USA, including relatively small sample size (109), strict inclusion criteria and a higher rate of adverse events (AEs) in the surgical arm (12% rate of anastomotic leakages and an 18% colostomy rate). The DIRECT trial also included less information about the outcomes for two important subgroups with QoL-limiting diverticulitis: those with concerns about recurrent episodes but no active symptoms and those with persistent symptoms after a resolved episode. The Comparison of Surgery and Medicine on the Impact of Diverticulitis (COSMID) trial, funded by the Patient-Centered Outcomes Research Institute, is a pragmatic, patient-level randomised superiority trial. It compares elective segmental colectomy with medical management strategies for patients with a history of left-sided diverticulitis and related QoL limitation. COSMID is conducted across a broad range of practice settings, including academic and community hospitals, incorporates a wide range of medical treatments and clinical care delivery modes and includes a heterogeneous patient population by clinical presentation and sociodemographic characteristics. The primary goal of the COSMID trial is to determine whether elective colectomy is more effective than medical management for patients with QoL-limiting diverticulitis. Additionally, as an exploratory goal, COSMID seeks to identify patient subgroups, delineated by specific Gastrointestinal Quality of Life Index score thresholds, who are more or less likely to benefit from either treatment. Trial design Patient and public involvement The COSMID trial incorporates interest holders’ input in its planning, design and implementation phases. The Interest Holder Coordinating Center (IHCC), established as an official core within the trial infrastructure, facilitates all interest holder involvement. The IHCC includes representatives from patient populations (ie, individuals with direct experience of living with diverticulitis or at risk for diverticulitis), healthcare professionals who manage diverticulitis (eg, acute care surgeons, gastroenterologists and colorectal surgeons), leaders of professional organisations (eg, the American College of Surgeons and the American Society of Colon and Rectal Surgeons) and researchers ( table 1 ). The IHCC was instrumental in developing the study protocol, including selecting primary and secondary outcomes. In addition to conventional clinical metrics, the COSMID trial includes outcome measures that are especially important to patients (diverticulitis-specific concerns, QoL, time away from work and out-of-pocket expenses) and employers (work absenteeism and productivity). 15 16 Since surgery is more invasive than medical management, interest holders suggested testing the hypothesis that surgical intervention is superior to medical management. Using a superiority framework, COSMID addresses the main evidence gap identified by patients, clinicians and in prior systematic reviews by including important patient-reported outcomes (PROs), clinical outcomes and healthcare utilisation outcomes. Interest holders have remained active partners throughout the study’s conduct. Table 1. Engagement activities conducted for study development. Engagement type Interest holders Purpose of engagement How input informed planning Virtual meetings Patient Advisory Network Roles and expectations for collaboration, feasibility for randomisation from patient perspective, identifying additional outcomes of interest, protocol for patient enrolment and partnership with other interest holders. Identified need for a centralised resource (website) to summarise current evidence on best medical management options. Surveys Patients and potential patients To obtain broad input on randomisation feasibility for the study. Established approximately 50% willingness to randomise among at-risk patients, informing sample size calculations (reduced to 30% expected based on a conservative estimate). 1:1 interviews; in-person meetings and videoconferences Surgeons Roles and expectations for collaboration, feasibility for randomisation from the surgeon/ER physician perspective, protocol for patient enrolment and partnership with other interest holders. Confirmed surgeon participation and willingness to randomise patients, established clinical metrics for stopping criteria and confirmed important clinical outcomes and time for follow-up. Videoconferences DIRECT trial investigators To obtain input into the feasibility of the study and hear about lessons learnt. Broadened inclusion criteria and revised the QoL instrument to assure comparability of the two trial populations and outcomes. Videoconferences National Advisory Board Roles and expectations for collaboration throughout the study, obtained input on study outcomes and interest in the respective community. Included a productivity measure as a secondary outcome. Open in a new tab Study aims and hypothesis COSMID aims to compare PROs (eg, time-averaged Gastrointestinal Quality of Life Index (GIQLI) score at 6, 9 and 12 months after randomisation, symptom burden, work productivity and decisional regret) 17 ; clinical outcomes (eg, rates of serious adverse events (SAEs) and number of subsequent episodes of diverticulitis); surgical outcomes (eg, complications of surgery and the disease) and healthcare utilisation measures (eg, time away from work, time in healthcare and out-of-pocket expenses) in participants with QoL-limiting left-sided diverticulitis who are randomised to elective colectomy versus medical management. We hypothesise that elective colectomy is superior to medical management for PROs (ie, GIQLI score (average at 6, 9 and 12 months after randomisation)). In the parallel observational cohort, we aim to evaluate the demographic and clinical characteristics of participants who decline randomisation but are willing to contribute information about the same outcomes. 18 We also aim to explore differences in PROs between participants in the randomised trial and those who selected their treatment. Methods This study protocol paper adhered to the reporting standards described in the Standard Protocol Items: Recommendations for Interventional Trials checklist. 19 Study population The study population includes adults with a history of left-sided diverticulitis and QoL limitation related to either recurrent AUD in remission (no symptoms) or persistent signs, symptoms and/or concerns after recovering from an episode of AUD and who speak English or Spanish. The study uses broad inclusion criteria to ensure that participants from different socioeconomic and demographic backgrounds are represented to improve the generalisability of the study findings. Using Thorpe’s Pragmatic-Explanatory Continuum Indicator Summary rubric for pragmatic trials, the proposed study is considered highly pragmatic, intended to improve the generalisation and precision of decision-making. 20 Inclusion criteria Adults ≥18 years. At least one episode of diverticulitis confirmed by a CT scan and a colonoscopy (completed or scheduled) to rule out or screen for other colon pathology in accordance with colorectal cancer screening guidelines. Persistent signs, symptoms or concerns related to diverticulitis after recovery from an episode of left-sided diverticulitis. Self-reported QoL limitation (assessed with 12 questions modified from the Diverticulitis Quality of Life (DV-QOL) 21 instrument). Exclusion criteria Unable to consent in English or Spanish. Current diagnosis or previous endoscopic or surgical interventions for fistula or stricture or current significant bleeding related to diverticulitis. Last episode of acute diverticulitis currently unresolved (ie, on antibiotics for diverticulitis; drain in place). Previous operation for diverticulitis. Right-sided diverticulitis. Immunodeficiency (eg, absolute neutrophil count <500/mm 3 , chronic immunosuppressive drugs like oral corticosteroids, anti-tumour necrosis factor (TNF) agents or known AIDS (ie, recent CD4 count <200) assessed by patient history). Actively undergoing chemotherapy or radiation for a malignancy. Expectant or concurrent haemodialysis, peritoneal dialysis, treatments using indwelling venous catheters or conditions putting the patient at risk for bacterial seeding. Diagnosis of inflammatory bowel disease (ie, Crohn’s, ulcerative colitis). Taking prescription medication for irritable bowel syndrome. Intolerance or allergy to all medications in the medical management arm. The surgeon is unwilling to offer surgery due to comorbid or prior surgical conditions that contraindicate elective surgery (eg, liver failure, renal failure, malignancy and ‘frozen abdomen’). Abdominal/pelvic surgery within the past month. Pregnant or expecting to become pregnant in the 30 days following baseline/screening. Unable to consent to research or self-respond to follow-up surveys (eg, altered mental status). Currently incarcerated in a detention facility or in police custody at baseline/screening (patients wearing a monitoring device can be enrolled). Prior enrolment in the COSMID study or planning on enrolment in another investigational drug or vaccine while on study treatment. Unable or unwilling to return, be contacted for or complete research surveys. Recruitment Patients with a history of left-sided diverticulitis and related QoL limitation are recruited for participation during their visit at participating surgical clinics in the USA. Patients with QoL limitation due to persistent signs, symptoms and/or concerns after recovering from an episode of diverticulitis or due to recurrent episodes of diverticulitis are identified by surgeons. Once identified as eligible, a member of the research team approaches potential participants to watch a standardised video providing information about diverticulitis, treatment options and the COSMID trial (becertain.org/cosmid-videos). Patients who decline randomisation are asked to participate in the observational cohort that includes the same baseline and follow-up measures as those in the randomised trial. All participants are asked for permission to be followed through passive electronic medical record review. COSMID recruitment began on 1 October 2019, at the University of Washington Medical Centre, with additional hospitals across the USA planned to begin recruitment in waves. It is possible that not all clinical sites will continue to contribute patients throughout the entire recruitment period (projected to end on 1 February 2026). Participant follow-up assessment Baseline surveys are collected after obtaining consent for the trial and before revealing the participant’s randomised treatment assignment. Research coordinators document if the participant became aware of their assignment before completing the baseline assessment. Survey questions are prioritised by importance to accommodate participants who may not complete the entire set of questionnaires. Participants are contacted quarterly, starting from 3 months postenrolment through 36 months, to complete study assessments using phone, mail or web-based surveys ( table 2 ). The outreach method is determined by the contact information provided by the participant and their preferred method of communication. Data collected from the electronic medical record are entered into a Research Electronic Data Capture (REDCap) database by site research coordinators. 22 23 The REDCap database is managed by the data coordinating centre (DCC) at the University of Washington. Table 2. Participant assessment schedule. Item Baseline Follow-up time point Year 1 Year 2 Year 3 * Month 3 6 9 12 15 18 21 24 27 30 33 36 Participant point of contact Site RT Baseline assessments X GIQLI 31 X X X X X X PROMIS Global Health 32 X X X X X DV-QOL instrument 21 X X X Work productivity 33 X X X X X X X Decision Regret Scale 34 X X Healthcare use X X X X X X X X X X X X Medical management X X X X X X X X X X X X Open in a new tab * Extended follow-up may be incorporated, pending funding. DV-QOL, Diverticulitis Quality of Life instrument; GIQLI, Gastrointestinal Quality of Life Index; PROMIS, Patient-Reported Outcomes Measurement Information System; RT, research team. If a participant requests to speak with a medical provider or reports concerning medical symptoms to the research team, the clinical team is notified, and the surgical site lead contacts the participant for additional follow-up. The DCC conducts regular quality assurance checks for issues such as missing values in required fields, incorrect data types, outliers, range checks, hidden fields with values and multiple-choice fields with invalid selections. Values that need correction are brought to the attention of site research staff for follow-up. Sites with protocol violations, missing data or participant loss to follow-up are referred to the executive committee to determine an action plan for protocol compliance and retention. Sites that do not meet the standards may be placed on probation or have their recruitment stopped. Study arms Surgical arm: elective segmental colectomy Participants in the surgical arm undergo resection of the involved segment of colon, with anticipation of primary anastomosis with or without protective ostomy. The principles of surgical treatment outlined by the American Society of Colon and Rectal Surgeons are recommended (eg, dissection to the true rectum, mobilisation of the splenic flexure as needed, resection of diseased portions of the colon and minimally invasive approach if possible). Sites involved in the trial routinely use perioperative antibiotics, bowel prep and Enhanced Recovery After Surgery protocols. As a pragmatic trial, surgical technique and perioperative care are not standardised. Surgeons are encouraged to perform the procedure within 6 weeks of randomisation, and the time from randomisation to the procedure is tracked. Non-surgical arm: medical management All patients randomised to medical management are asked to watch a 4-min video providing standardised information on three components of medical management: (1) diet and exercise, (2) supplements (eg, probiotics) and (3) medications (eg, mesalamine, rifaximin). The video describes each component, its mechanism of action, evidence and other factors related to each intervention. All participants receive recommendations for a regimen of diet, exercise and fibre supplementation based on current guidelines. 13 Surgeons initiate treatments with supplements and/or medications following shared decision-making discussions with participants. As a pragmatic trial, the specific progression of the components of medical management is not standardised. Surgeons are encouraged to initiate medical management soon after randomisation and to add components of the medical management toolbox for participants who have continued symptoms or recurrences. Surgeons are encouraged to continue medical management for at least 6 months after randomisation, but this is not stipulated. Participants who experience recurrent symptoms of diverticulitis are treated either in the outpatient or inpatient setting (including emergency surgery as needed) as determined by clinicians, using existing clinical guidelines. 13 Participants who are randomised to the medical management arm and who have elective surgery within 6 months are considered ‘crossovers’, and the indication is captured. Blinding and randomisation This is an unblinded study, as participants will know if they are randomised to receive elective colectomy or medical management. A separate DCC at the University of Washington generates and maintains randomisation lists for each site. The DCC uses block randomisation within the site, with randomly permuted blocks of size 2, 4, 6 or 8 participants. The use of block randomisation ensures that equal numbers of participants are randomised to each arm and that the two groups are balanced at enrolment intervals. The computer-generated random assignments are conveyed from the DCC to each clinical site through the secure study portal after verification of eligibility criteria and patient consent. Outcomes and measures The primary outcome is the time-averaged score of the GIQLI average at 6, 9 and 12 months after randomisation in the intention-to-treat (ITT) population. Secondary PROs include the DV-QOL instrument, the Patient-Reported Outcomes Measurement Information System Global Health measure, the Decision Regret Scale and the Work Productivity and Activity Impairment instrument. Clinical endpoints include recurrent episodes of diverticulitis and SAEs, which are life-threatening complications defined using the National Surgical Quality Improvement Program (NSQIP) criteria, or death related to diverticulitis treatment, taken as a binary event (SAE vs no SAE). Healthcare utilisation endpoints include the number of emergency room visits, ambulatory care office visits, hospital admission, length of hospital stay, recurrent elective and emergency surgery and related care, which are obtained at quarterly intervals. Complications in both treatment groups are tracked and adjudicated by an independent safety monitor to determine their relation to the disease and treatment. Sample size and power calculation The study sample size was calculated based on the projected (or hypothesised) difference in GIQLI between the two treatment interventions. A between-group difference in the GIQLI score of 10 has previously been established as the minimal clinically important difference (MCID). 24 25 The study sample size was motivated to provide >80% power to detect a 10-point difference overall and to be able to detect such a difference within subgroups as small as 30% of the overall study sample size. Data from the DIRECT trial were used to inform the SD in each group (22.3 in the surgical arm and 22.7 in the medical management arm) as well as the mean for medical management (100.4). 26 Conservatively assuming up to 33% of participants will miss one of the three outcome assessments, and 33% will miss two assessments, we assumed a calculated SD of 20 points for the time-averaged GIQLI score at 6, 9 and 12 months after randomisation. Assuming a type 1 error rate of 0.05 for the primary comparison and a correlation coefficient of 0.5 between baseline and follow-up GIQLI scores, 47 participants in each group are required to detect a 10-point difference in GIQLI. Accounting for a conservative estimated dropout of 10% at 6 months requires randomising 52 participants to each arm (n=104). We will randomise 250 participants. This sample size will provide >80% power to detect an overall difference in GIQLI of 5.5 points and an MCID of 10 within participant subgroups with proportions of ~30% ( table 3 ). The observational cohort will include 100 participants (50 medical management and 50 surgical). This number was selected to allow for comparisons in participant characteristics between randomised and treatment-selecting participants and to explore differences in outcomes between treatment groups and between randomised and treatment-selecting participants. Table 3. Prioritised list of subgroups and anticipated proportion. Subgroup Anticipated proportion Source Age (<50) 33% Wheat and Strate 35 Presentation (recurrent episodes) 37% DIRECT trial 26 QoL impairment at baseline (GIQLI <92) 50% DIRECT trial 26 Sex (male) 36% DIRECT trial 26 Open in a new tab GIQLI, Gastrointestinal Quality of Life Index; QoL, quality of life. Statistical analysis The DCC will assess the primary outcome of time-averaged GIQLI score at 6, 9 and 12 months after randomisation using an analysis of covariance (ANCOVA) regression model that adjusts for an indicator of randomised treatment group, the GIQLI score as measured at baseline prior to randomisation, and factors used to stratify randomisation (recruitment site). Specifically, the analysis will be conducted using three methods. The primary method will use data as entered, regardless of missing individual components of the GIQLI and/or missing GIQLI scores. The second method will impute missing components of the GIQLI score with the participant-level average. The third method will include two imputations. First, multivariate imputation by chained equations (MICE) will replace missing individual components of the GIQLI using the remaining 35 components. 27 Second, MICE will replace missing GIQLI scores using a set of demographic variables (ie, participant age, number of years with diverticulitis, etc) that best predict the outcome and/or missingness of scores. 28 Treatment estimates will be pooled across 10 imputed datasets. While some crossover to elective colectomy in the medical management group is likely to occur, an ITT will be the primary analytic approach. As a secondary analysis, we will use complier average causal effect 29 and, separately, a maximum likelihood mixture modelling approach to examine two aspects of the intervention process: the prediction of crossover in the elective colectomy group and the examination of the treatment effect on QoL among participants who are suitable candidates for medical management. Time trajectories of the GIQLI and other PROs at all follow-up time points will be evaluated using linear mixed models, adjusting for an indicator of randomised treatment group assignment and recruitment site. We will evaluate rates of self-reported, recurrent diverticulitis (with review of available medical record documentation as confirmation) and SAEs. Clinical endpoints and types of healthcare utilisation will be compared between ITT groups using appropriate generalised linear models for each outcome variable. Differences at baseline and PRO response between participants in the randomised and observational cohorts will be compared using linear regression models (for single time points) and linear mixed effects models (for trajectories of response), adjusting for an indicator of treatment, randomisation status and factors found to be statistically significantly different between the two groups. We will further analyse differences in the time-averaged outcome regarding the magnitude of treatment effect modification across candidate characteristics selected by participants and clinical advisors. Specifically, from the ANCOVA model, we will estimate the difference in treatment effect across subgroups using an interaction term between treatment group and subgroup while adjusting for site. Data safety and monitoring Event reporting Death, life-threatening events and rehospitalisation are classified as SAEs. 30 Morbidity events (using modified definitions from NSQIP to accommodate non-operative care) are considered AEs. SAEs and AEs are identified by electronic medical record review, participant surveys or reporting by any research or care team member. All SAEs are adjudicated by an independent safety monitor. SAEs and AEs are reviewed by an independent data and safety monitoring board (DSMB) biannually (except for death, which is reported to the DSMB within 24 hours). The DSMB reviews the accruing data to (1) ensure the adequacy of study conduct, enrolment and participant follow-up; (2) identify and address any potential serious safety concerns and (3) assess the evidence pertaining to patient-reported QoL. The analysis of accruing data is completed by the DCC, and interim analysis is presented to the DSMB with the primary goal of monitoring safety outcomes by randomisation group. The COSMID trial does not include a stopping rule because there are important secondary outcomes (eg, rate of diverticulitis recurrence, complications and healthcare utilisation) and understudied subgroups that require full enrolment. No stopping rules are proposed for either efficacy or safety since both treatment arms studied under the COSMID trial protocol reflect treatments available under the standard of care. Ethics and dissemination This trial was approved by the Vanderbilt Institutional Review Board (IRB) on 26 August 2019 (IRB #191217). Vanderbilt serves as the institutional review board of record for the following study sites: Albany Medical College, Allegheny Health, Atrium Health Carolinas Medical Center, Virginia Mason Medical Center, Boston University Medical Center, Cedars-Sinai Medical Center, UT Health Lyndon B. Johnson Hospital, Medical University of South Carolina, New York-Presbyterian Queens, Stanford University, University of Pennsylvania, University of California San Diego, University of California San Francisco, University of Colorado Denver, University of Florida, University of Iowa, University of Utah, University of Washington Medical Center, University of South Florida, University of Rochester Medical Center, University of Texas Southwestern Medical Center, Virginia Commonwealth University, Lahey Hospital & Medical Center, Weill Cornell Medical Center and Northwell Health. Rush University Medical Center (approved 8 January 2020), Columbia University Medical Center (approved 28 January 2020), Northwestern University (approved 19 March 2020), Mount Carmel Health System (approved 5 May 2020) and Memorial Health University Medical Center (approved 4 April 2022) are regulated and were approved by their respective IRBs. Results from this trial will be presented at international conferences and published in peer-reviewed journals. The views presented in this work are solely the responsibility of the author(s) and do not necessarily represent the views of PCORI, its Board of Governors or Methodology Committee. Footnotes Funding: Research reported in this article was funded through a Patient-Centered Outcomes Research Institute (PCORI) Award (PCS-2018C1-10949), from 06/01/2019 to 05/01/2028. Prepublication history for this paper is available online. To view these files, please visit the journal online ( https://doi.org/10.1136/bmjopen-2024-098309 ). Patient consent for publication: Not applicable. Provenance and peer review: Not commissioned; externally peer reviewed. Collaborators: The following are members of the writing group of the COSMID Collaborative: Mariam N Hantouli, MD; Robert H Schmicker, MS; Janice E Tufte, LE; Fadwa G Ali, MD; Robert D Bennett, MD; Jessica N Cohan, MD, MAS; Bryan A Comstock, MS; Thomas Curran, MD, MPH; Giana H Davidson, MD, MPH; Samuel Eisenstein, MD; Katherine N Fischkoff, MD, MPA, MSc; Fergal Fleming, MD, MPH; Irena Gribovskaja-Rupp, MD; Mehraneh Dorna Jafari, MD; Larry G Kessler, Sc.D.; Mukta K Krane, MD; Sarah O Lawrence, MA; James T McCormick, DO; Stefanos G Millas, MD; Arden M Morris, MD, MPH; Kelsey M Pullar, MPH; Caroline E Reinke, MD, MSHP, MSPH; Julia Saraidaridis, MD, MMSc; Vlad V. Simianu, MD, MPH; Suzanne P Watkins, BS; Nicole B White, MD; Elizabeth C Wick, MD; Nicole Wieghard, MD; David R Flum, MD, MPH; Thomas E Read, MD. Patient and public involvement: Patients and/or the public were involved in the design, conduct, reporting or dissemination plans of this research. Refer to the Trial design section for further details. Map disclaimer: The depiction of boundaries on this map does not imply the expression of any opinion whatsoever on the part of BMJ (or any member of its group) concerning the legal status of any country, territory, jurisdiction or area or of its authorities. This map is provided without any warranty of any kind, either express or implied. Contributor Information COSMID Collaborative: Mariam N Hantouli , Robert H Schmicker , Janice E Tufte , Fadwa G Ali , Robert D Bennett , Jessica N Cohan , Bryan A Comstock , Thomas Curran , Giana H Davidson , Samuel Eisenstein , Katherine N Fischkoff , Fergal Fleming , Irena Gribovskaja-Rupp , Mehraneh Dorna Jafari , Larry G Kessler , Mukta K Krane , Sarah O Lawrence , James T McCormick , Stefanos G Millas , Arden M Morris , Kelsey M Pullar , Caroline E Reinke , Julia Saraidaridis , Vlad V Simianu , Suzanne P Watkins , Nicole B White , Elizabeth C Wick , Nicole Wieghard , David R Flum , and Thomas E Read References 1. Peery AF, Dellon ES, Lund J, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology. 2012;143:1179–87. doi: 10.1053/j.gastro.2012.08.002. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 2. Peery AF, Crockett SD, Murphy CC, et al. Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2018. Gastroenterology. 2019;156:254–72. doi: 10.1053/j.gastro.2018.08.063. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 3. Bollom A, Austrie J, Hirsch W, et al. Emergency Department Burden of Diverticulitis in the USA, 2006-2013. Dig Dis Sci. 2017;62:2694–703. doi: 10.1007/s10620-017-4525-y. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 4. Kozak LJ, DeFrances CJ, Hall MJ. National hospital discharge survey: 2004 annual summary with detailed diagnosis and procedure data. Vital Health Stat 13. 2006:1–209. [ PubMed ] [ Google Scholar ] 5. van Dijk ST, Daniels L, Ünlü Ç, et al. Long-Term Effects of Omitting Antibiotics in Uncomplicated Acute Diverticulitis. Am J Gastroenterol. 2018;113:1045–52. doi: 10.1038/s41395-018-0030-y. [ DOI ] [ PubMed ] [ Google Scholar ] 6. Desai M, Fathallah J, Nutalapati V, et al. Antibiotics Versus No Antibiotics for Acute Uncomplicated Diverticulitis: A Systematic Review and Meta-analysis. Dis Colon Rectum. 2019;62:1005–12. doi: 10.1097/DCR.0000000000001324. [ DOI ] [ PubMed ] [ Google Scholar ] 7. Mora-López L, Ruiz-Edo N, Estrada-Ferrer O, et al. Efficacy and Safety of Nonantibiotic Outpatient Treatment in Mild Acute Diverticulitis (DINAMO-study): A Multicentre, Randomised, Open-label, Noninferiority Trial. Ann Surg . 2021;274:e435–42. doi: 10.1097/SLA.0000000000005031. [ DOI ] [ PubMed ] [ Google Scholar ] 8. Roberts P, Abel M, Rosen L, et al. Practice parameters for sigmoid diverticulitis. Diseases of the Colon & Rectum. 1995;38:125. doi: 10.1007/BF02052438. [ DOI ] [ PubMed ] [ Google Scholar ] 9. Hall J, Hardiman K, Lee S, et al. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Left-Sided Colonic Diverticulitis. Dis Colon Rectum. 2020;63:728–47. doi: 10.1097/DCR.0000000000001679. [ DOI ] [ PubMed ] [ Google Scholar ] 10. Dichman ML, Rosenstock SJ, Shabanzadeh DM. Antibiotics for uncomplicated diverticulitis. Cochrane Database Syst Rev. 2022;6:CD009092. doi: 10.1002/14651858.CD009092.pub3. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 11. Hantouli MN, Droullard DJ, Strate LL, et al. Optimizing medical management for diverticular disease: A systematic review and gap analysis. Seminars in Colon and Rectal Surgery. 2020;31:100782. doi: 10.1016/j.scrs.2020.100782. [ DOI ] [ Google Scholar ] 12. Stollman N, Smalley W, Hirano I, et al. American Gastroenterological Association Institute Guideline on the Management of Acute Diverticulitis. Gastroenterology. 2015;149:1944–9. doi: 10.1053/j.gastro.2015.10.003. [ DOI ] [ PubMed ] [ Google Scholar ] 13. Feingold D, Steele SR, Lee S, et al. Practice Parameters for the Treatment of Sigmoid Diverticulitis. Dis Colon Rectum. 2014;57:284–94. doi: 10.1097/DCR.0000000000000075. [ DOI ] [ PubMed ] [ Google Scholar ] 14. Bolkenstein HE, Consten ECJ, van der Palen J, et al. Long-term Outcome of Surgery Versus Conservative Management for Recurrent and Ongoing Complaints After an Episode of Diverticulitis: 5-year Follow-up Results of a Multicenter Randomized Controlled Trial (DIRECT-Trial) Ann Surg. 2019;269:612–20. doi: 10.1097/SLA.0000000000003033. [ DOI ] [ PubMed ] [ Google Scholar ] 15. Hantouli MN, Khor S, Strate LL, et al. What’s in a Number? Assessing the Burden of Diverticular Disease. Ann Surg Open . 2022;3:e202. doi: 10.1097/AS9.0000000000000202. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 16. Hantouli MN, Droullard DJ, Khor S, et al. Indications for surgical treatment of diverticulitis: factors that influence surgical decision-making for patients and surgeons. Br J Surg. 2022;109:1329–30. doi: 10.1093/bjs/znac321. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 17. Calvert M, Kyte D, Mercieca-Bebber R, et al. Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trial Protocols: The SPIRIT-PRO Extension. JAMA. 2018;319:483–94. doi: 10.1001/jama.2017.21903. [ DOI ] [ PubMed ] [ Google Scholar ] 18. Writing Group for the CODA Collaborative. Davidson GH, Monsell SE, et al. Self-selection vs Randomized Assignment of Treatment for Appendicitis. JAMA Surg. 2022;157:598–608. doi: 10.1001/jamasurg.2022.1554. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 19. Chan A-W, Tetzlaff JM, Altman DG, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158:200–7. doi: 10.7326/0003-4819-158-3-201302050-00583. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 20. Thorpe KE, Zwarenstein M, Oxman AD, et al. A pragmatic-explanatory continuum indicator summary (PRECIS): a tool to help trial designers. J Clin Epidemiol. 2009;62:464–75. doi: 10.1016/j.jclinepi.2008.12.011. [ DOI ] [ PubMed ] [ Google Scholar ] 21. Spiegel BMR, Reid MW, Bolus R, et al. Development and validation of a disease-targeted quality of life instrument for chronic diverticular disease: the DV-QOL. Qual Life Res. 2015;24:163–79. doi: 10.1007/s11136-014-0753-1. [ DOI ] [ PubMed ] [ Google Scholar ] 22. Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377–81. doi: 10.1016/j.jbi.2008.08.010. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 23. Harris PA, Taylor R, Minor BL, et al. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019;95:103208. doi: 10.1016/j.jbi.2019.103208. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 24. Forgione A, Leroy J, Cahill RA, et al. Prospective evaluation of functional outcome after laparoscopic sigmoid colectomy. Ann Surg. 2009;249:218–24. doi: 10.1097/SLA.0b013e318195c5fc. [ DOI ] [ PubMed ] [ Google Scholar ] 25. Zdichavsky M, Granderath FA, Blumenstock G, et al. Acute laparoscopic intervention for diverticular disease (AIDD): a feasible approach. Langenbecks Arch Surg. 2010;395:41–8. doi: 10.1007/s00423-008-0433-0. [ DOI ] [ PubMed ] [ Google Scholar ] 26. van de Wall BJM, Stam MAW, Draaisma WA, et al. Surgery versus conservative management for recurrent and ongoing left-sided diverticulitis (DIRECT trial): an open-label, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol. 2017;2:13–22. doi: 10.1016/S2468-1253(16)30109-1. [ DOI ] [ PubMed ] [ Google Scholar ] 27. Mazza GL, Enders CK, Ruehlman LS. Addressing Item-Level Missing Data: A Comparison of Proration and Full Information Maximum Likelihood Estimation. Multivariate Behav Res. 2015;50:504–19. doi: 10.1080/00273171.2015.1068157. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 28. Azur MJ, Stuart EA, Frangakis C, et al. Multiple imputation by chained equations: what is it and how does it work? Int J Methods Psychiatr Res. 2011;20:40–9. doi: 10.1002/mpr.329. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 29. Angrist JD, Imbens GW. Two-Stage Least Squares Estimation of Average Causal Effects in Models with Variable Treatment Intensity. J Am Stat Assoc. 1995;90:431–42. doi: 10.1080/01621459.1995.10476535. [ DOI ] [ Google Scholar ] 30. Cohen ME, Bilimoria KY, Ko CY, et al. Development of an American College of Surgeons National Surgery Quality Improvement Program: morbidity and mortality risk calculator for colorectal surgery. J Am Coll Surg. 2009;208:1009–16. doi: 10.1016/j.jamcollsurg.2009.01.043. [ DOI ] [ PubMed ] [ Google Scholar ] 31. Eypasch E, Williams JI, Wood-Dauphinee S, et al. Gastrointestinal Quality of Life Index: development, validation and application of a new instrument. Br J Surg. 1995;82:216–22. doi: 10.1002/bjs.1800820229. [ DOI ] [ PubMed ] [ Google Scholar ] 32. Amtmann D, Cook KF, Jensen MP, et al. Development of a PROMIS item bank to measure pain interference. Pain. 2010;150:173–82. doi: 10.1016/j.pain.2010.04.025. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 33. Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics. 1993;4:353–65. doi: 10.2165/00019053-199304050-00006. [ DOI ] [ PubMed ] [ Google Scholar ] 34. Brehaut JC, O’Connor AM, Wood TJ, et al. Validation of a decision regret scale. Med Decis Making. 2003;23:281–92. doi: 10.1177/0272989X03256005. [ DOI ] [ PubMed ] [ Google Scholar ] 35. Wheat CL, Strate LL. Trends in Hospitalization for Diverticulitis and Diverticular Bleeding in the United States From 2000 to 2010. Clin Gastroenterol Hepatol. 2016;14:96–103. doi: 10.1016/j.cgh.2015.03.030. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] BMJ Open. 2026 Jan 8. Review Process File Copyright and License information PMC Copyright notice bmjopen-2024-098309.reviewer_comments.pdf (225KB, pdf) Open in a new tab Articles from BMJ Open are provided here courtesy of BMJ Publishing Group ACTIONS View on publisher site PDF (425.3 KB) Cite Collections Permalink PERMALINK Copy RESOURCES Similar articles Cited by other articles Links to NCBI Databases Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM Add to Collections Create a new collection Add to an existing collection Name your collection * Choose a collection Unable to load your collection due to an error Please try again Add Cancel Follow NCBI NCBI on X (formerly known as Twitter) NCBI on Facebook NCBI on LinkedIn NCBI on GitHub NCBI RSS feed Connect with NLM NLM on X (formerly known as Twitter) NLM on Facebook NLM on YouTube National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA HHS Vulnerability Disclosure Help Accessibility Careers NLM NIH HHS USA.gov Back to Top