Date of Award

January 2023

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Jonathan N. Grauer

Abstract

Clinical trials are key to the advancement of products and procedures related to musculoskeletal conditions. Unfortunately, many trials are terminated prior to completion. ClinicalTrials.gov is a registry and results database maintained by the National Library of Medicine that catalogs trial characteristics and tracks overall recruitment status (e.g., ongoing, completed, terminated) for each study as well as reasons for termination. Reasons for termination have not been specifically evaluated for musculoskeletal trials and those related to the spine and shoulder/elbow were selected for characterization and assessment of independent predictors of termination by comparing characteristics of completed and terminated trials.

The ClinicalTrials.gov database was queried for all completed and terminated interventional studies using search terms built into the ClinicalTrials.gov search engine related to the spine on June 20, 2021 and those related to the shoulder/elbow on August 6, 2021, respectively. Trial characteristics and reasons for termination were abstracted. Univariate and multivariate analyses were performed to determine independent predictors of trial termination.

For clinical trials related to the spine, a total of 969 were identified and characterized, of which 136 (14%) were terminated. Insufficient rate of participant accrual was the most frequently reported reason for trial termination, accounting for 33.8% of terminated trials. Multivariate analysis demonstrated increased odds of trial termination for industry-sponsorship (odds ratio [OR] = 1.59) relative to sponsorship from local groups, device studies (OR = 2.18) relative to investigations of drug or biological product(s), and phase II (OR = 3.07) relative to phase III studies (p < 0.05 for each).

For clinical trials related to the shoulder, a total of 662 were identified and characterized, of which 51 (8%) were terminated. Difficulties with participant recruitment and/or retention was the individual reason most frequently reported for trial termination, accounting for 51% of terminated clinical trials related to the shoulder. For clinical trials related to the shoulder, multivariate analysis of primary trial characteristics demonstrated increased odds of trial termination for industry-sponsorship (OR = 4.2, p = 0.001) relative to sponsorship from local groups, and blinded studies (OR = 45.8, p = 0.0003) relative to studies that did not implement any form of blinding.

For clinical trials related to the elbow, a total of 126 were identified and characterized, of which 16 (13%) were terminated. Difficulties with participant recruitment and/or retention was the individual reason most frequently reported for trial termination, accounting for 38% of terminated clinical trials related to the elbow. For clinical trials related to the elbow, logistic regression did not reveal any of the primary trial characteristics evaluated to be correlated with odds of termination.

Clinical trials related to the spine, shoulder, and elbow were terminated at a rate of 14%, 8%, and 13%, respectively. Overall, difficulties in the recruitment and/or retention of trial participants was the reason most frequently reported for trial termination. With significant resources put into clinical trials and the need to advance scientific objectives, independent predictors and reasons for trial termination should be considered and addressed, when possible, to optimize the completion rate of trials that are initiated.

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This is an Open Access Thesis.

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