Cost Resulting from Anti-Tuberculosis Drug Shortages in the United States: A Hypothetical Cohort Study.
BACKGROUND
From 2012 through 2014, the United States experienced acute shortages and price escalations of several first-line anti-tuberculosis (TB) medications. Because secondary TB drug regimens are longer and adverse events occur more frequently with them, we sought to conservatively estimate the cost, to patients and the health care system, of TB treatment and medication adverse events from alternative regimens during drug shortages.


METHODS
We assessed the cost of treatment for TB disease in the absence of isoniazid (INH), rifampin (RIF), or pyrazinamide (PZA), or both INH and RIF. We simulated adverse events based on published probabilities using a monthly discrete-time stochastic model. For total costs, we summed costs of medications, routine testing, and treatment of adverse events using procedural terminology codes. We report average cost ratios of TB treatment during drug shortages to standard TB treatment.


RESULTS
The cost ratio of TB treatment without INH, RIF, or PZA to standard treatment was 1.7 (Range: 1.2, 2.3), 4.9 (Range: 3.2, 7.3), and 1.1 (Range: 0.7, 1.7) times higher, respectively. Without both INH and RIF, the cost ratio was 18.6 (Range: 10.0, 39.0) times higher. When the prices for INH, RIF and PZA were increased, the cost for standard treatment increased by a factor of 2.7 (Range: 1.9, 3.0). The percentage of patients experiencing at least one adverse event while taking standard therapy was 3.9% (Range: 1.3%, 11.8%). This percentage increased to 51.5% (Range: 20.1%, 83.8%) when RIF was unavailable, and increased to 82.5% (Range: 41.2%, 98.5%) when both INH and RIF were unavailable.


CONCLUSIONS
Our conservative model illustrates that an interruption in first-line anti-TB medications leads to appreciable additional costs and adverse events for patients. The availability of these drugs in the United States should be ensured. Models that incorporate the effectiveness of alternative regimens, delays in treatment initiation, and TB transmission can provide broader perspectives on the impact of drug shortages.
Colby College, Department of Mathematics and Statistics, Waterville, Maine, United States of America; Francis I. Proctor Foundation, San Francisco, California, United States of America.
James C
JC
Scott
California Department of Health Tuberculosis Control Branch, Richmond, California, United States of America; Centers for Disease Control and Prevention, Division of Tuberculosis Elimination, Atlanta, Georgia, United States of America.
Neha
N
Shah
Francis I. Proctor Foundation, San Francisco, California, United States of America; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
Travis
T
Porco
California Department of Health Tuberculosis Control Branch, Richmond, California, United States of America.
Jennifer
J
Flood
D000995:Antitubercular Agents / Q000191:economics* / Q000600:supply & distribution* / Q000627:therapeutic use; D015331:Cohort Studies; D006801:Humans; D015233:Models, Statistical; D040841:Resource Allocation; D013269:Stochastic Processes; D014376:Tuberculosis / Q000188:drug therapy; D014481:United States
D000995:Antitubercular Agents