Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Apr 12, 2020; 11(2): 32-42
Published online Apr 12, 2020. doi: 10.4291/wjgp.v11.i2.32
Outcomes of a drug shortage requiring switching in patients with ulcerative colitis
Daniel R van Langenberg, Richard Kai-Yuan Cheng, Mayur Garg
Daniel R van Langenberg, Richard Kai-Yuan Cheng, Mayur Garg, Department of Gastroenterology, Eastern Health, Box Hill, Victoria 3128, Australia
Daniel R van Langenberg, Mayur Garg, Eastern Health Clinical School, Monash University, Box Hill, Victoria 3128, Australia
Richard Kai-Yuan Cheng, Department of Gastroenterology, Redcliffe Hospital, Redcliffe, Queensland 4020, Australia
Mayur Garg, Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Victoria 3052, Australia
Author contributions: van Langenberg DR conceived and designed the work, plus contributed to the collection, analysis and interpretation of data and drafting of the manuscript; Cheng RKY contributed to the collection of data and to drafting the manuscript; Garg M contributed to the design and contributed to analysis and interpretation of data, plus drafting the manuscript; all authors approved the final version of the manuscript.
Institutional review board statement: This study was approved as a low-risk application by the Eastern Health Office for Human Research & Ethics.
Informed consent statement: Patient consent was not deemed to be required for this non-interventional observational study using deidentified data.
Conflict-of-interest statement: All authors have no conflicts of interest to declare in relation to this work.
Data sharing statement: Not applicable.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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 and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Daniel R van Langenberg, FRACP, MBBS, PhD, Associate Professor, Head of IBD, Gastroenterologist, Department of Gastroenterology, Eastern Health, 8 Arnold Street, Box Hill, Victoria 3128, Australia. daniel.van-langenberg@monash.edu
Received: November 12, 2019
Peer-review started: November 12, 2019
First decision: December 23, 2019
Revised: March 4, 2020
Accepted: March 12, 2020
Article in press: March 12, 2020
Published online: April 12, 2020
Processing time: 148 Days and 7.3 Hours
ARTICLE HIGHLIGHTS
Research background

Drug shortages appear to be occurring more frequently, yet their clinical impact and sequelae are not yet well described. Here, a nationwide drug shortage of balsalazide occurred over several months in 2012-3, necessitating a sudden switch to alternative aminosalicyclate formulations.

Research motivation

In this study the impact of this balsalazide shortage was intensively assessed in a well characterized population of patients with ulcerative colitis over a five year period to assess short and long term effects of a drug shortage. We hypothesized that this and similar drug shortages can have significant detrimental impacts on disease course and patient outcomes.

Research objectives

This study aimed to elucidate the short and long term ramifications of a drug shortage in ulcerative colitis patients on (1) efficacy (including symptom-based, and objective disease assessments); (2) safety (including immediate adverse effects occurring after switching to alternative agents); and (3) the proportion of patients returning to the original product once supply resumed as a measure of loss of market share. This comprehensive, holistic assessment of drug shortage-related outcomes sets a benchmark for further quantitative research in this field.

Research methods

A prospective cohort study of patients on balsalazide for mild-moderate ulcerative colitis was conducted where, strictly due to the national shortage patients were switched to alternative 5-ASA and/or then returned to balsalazide once supply resumed. Clinical and disease activity assessments were performed at baseline pre-switch, then immediately and at 3 and 5 years after the drug shortage-imposed switch to assess short and long term sequelae.

Research results

Although in stable remission at the time of the drug shortage, almost half of the patients when switched from balsalazide had documented clinical worsening at their subsequent review, including several reporting side effects to the alternative formulation. Only a minority of patients returned to balsalazide after drug supply returned, equating to a loss of market share (within the same class) of approximately 40% even to five years post-shortage in this cohort. These data highlight the importance of maintaining a seamless drug supply for both patients (given significant rates of disease worsening occurred, directly attributable to shortage), and drug manufacturers given the loss of market share engendered by even a short term drug shortage.

Research conclusions

In one of the first published studies of its kind to date, this study of a balsalazide shortage in UC patients exemplifies the detrimental impact of a drug shortage on long term patient, disease and commercial outcomes. Hence, patients, clinicians and drug manufacturers should be more aware and explore ways to address and minimize this growing problem worldwide.

Research perspectives

Further prospective, larger scale studies are needed to document the impacts of drug shortages in patients across multiple chronic and/or life-threatening diseases. By documenting the scope of this problem in this manner, hopefully long term solutions can then be instituted accordingly.