Branded 17-alpha hydroxyprogesterone caproate was introduced to the market in 2011.
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Fried I, Beam AL, Kohane IS, Palmer NP. Utilization, Cost, and Outcome of Branded vs Compounded 17-Alpha Hydroxyprogesterone Caproate in Prevention of Preterm Birth. JAMA Intern Med. 2017;177(11):1689–1690. doi:10.1001/jamainternmed.2017.5017
The drug 17-alpha hydroxyprogesterone caproate is an injectable synthetic progestin. It has been proven effective in preventing or delaying preterm birth in singleton pregnancies for women with a history of spontaneous preterm birth.1 Once widely available as an inexpensive compounded drug, it now has a branded version (Makena; AMAG Pharmaceuticals) that costs approximately 100 times more than the original. On February 4, 2011, KV Pharmaceutical Company (later renamed Lumara) received approval from the US Food and Drug Administration to manufacture and market Makena, which is composed of the same active ingredients as found in the original compounded formulation. The approval included an orphan drug designation and gave KV Pharmaceutical Company the exclusive rights to manufacture Makena, which potentially contributed to its high listed price.2 For this study, we used an insurance claims database to examine prescriptions for 17-alpha hydroxyprogesterone caproate among nearly 4000 commercially insured (not Medicaid) pregnant women. Our aim was to understand the use, costs, and outcomes of the branded and compounded versions of the drug.
We searched a deidentified insurance claims database of individuals who had medical and pharmacy coverage through a large national private insurance provider from January 1, 2008, to December 31, 2015. This study was approved by the Harvard Medical School Institutional Review Board. Consent to use the data was included in the approval, and no patients were directly contacted.
To characterize trends in utilization of branded and compounded 17-alpha hydroxyprogesterone caproate, we used National Drug Code descriptors to identify women who had a pharmacy claim for either the branded or the compounded formulation. In addition, using a unique Current Procedural Terminology code, we identified women who received an injection of the compounded drug from a homecare agency. We used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and Tenth Revision, Clinical Modification (ICD-10-CM) codes to restrict the study to women whose outcome of delivery was a single liveborn or stillborn (ICD-9-CM V27.0 and V.27.1; ICD-10-CM Z37.0 and Z37.1). All analyses were performed on this cohort of women.
To characterize costs, we calculated the total allowed cost for each woman from the first injection of 17-alpha hydroxyprogesterone caproate to delivery. This cost reflected the final negotiated price before any discounts were applied.
To characterize outcomes associated with utilization of branded and compounded 17-alpha hydroxyprogesterone caproate, we compared rates of preterm birth using logistic regression that controlled for maternal age. Preterm deliveries were identified using ICD-9-CM codes 644.2, 644.20, and 644.21 as well as ICD-10-CM codes O42.011 to O42.919 and O60.10 to O60.10X9.
From January 1, 2008, to December 31, 2015, a total of 535 women (540 pregnancies) received the branded drug and 3350 women (3481 pregnancies) received the compounded drug (Table). Use of both formulations rose over time until a 2015 decline in utilization of the compounded drug (Figure). The mean (SD) per pregnancy costs were $10 917 ($4248) for the branded drug and $206 ($115) for the compounded drug. No statistically significant difference in the rate of preterm birth was found between women receiving the branded drug and women receiving the compounded drug (odds ratio, 0.99; 95% CI, 0.95-1.02; P = .61).
Despite the branded drug costing a mean 5200% more than the compounded drug ($10 917 vs $206), the use of both formulations to prevent or delay preterm birth increased among our study population, with the exception of a 2015 decline in utilization of the compounded drug. Our examination of treatment efficacy was based on observational data and yielded findings that are consistent with those in previous reports3: Preterm birth rates did not differ between the 2 versions of 17-alpha hydroxyprogesterone caproate. In addition, the frequency of infections during treatment regimens was equally low in both groups, although it has been reported that compounded drugs may carry an increased risk for adverse events.4 Lastly, our study may not be generalizable to Medicaid beneficiaries, who may be at greater risk of preterm birth.
This analysis raises concerns about the value of branded 17-alpha hydroxyprogesterone caproate. A 2005 study of compounded 17-alpha hydroxyprogesterone caproate estimated that one-third of all preterm births could be prevented if the drug were administered to the 133 000 women who were eligible to receive it.5 According to our analysis, if given to every eligible woman, the branded version would cost more than $1.4 billion annually, whereas the compounded version would cost $27.5 million annually. This finding broadly illustrates that branded drugs with market exclusivity have become one of the primary drivers of rising medication costs.6
Corresponding Author: Andrew L. Beam, PhD, Department of Biomedical Informatics, Harvard Medical School, 10 Shattuck St, Boston, MA 02115 (firstname.lastname@example.org).
Accepted for Publication: July 27, 2017.
Published Online: October 2, 2017. doi:10.1001/jamainternmed.2017.5017
Author Contributions: Mr Fried and Dr Beam had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Mr Fried and Dr Beam contributed equally.
Study concept and design: Fried, Beam.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Fried, Beam.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Fried, Beam.
Obtained funding: Kohane.
Administrative, technical, or material support: Kohane, Palmer.
Study supervision: Beam, Kohane, Palmer.
Conflict of Interest Disclosures: Mr Fried and Dr Palmer reported receiving salary support from the Aetna Life Insurance Company as part of the Aetna Research Collaboration with Harvard Medical School. No other disclosures were reported.
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