Date of Award


Degree Type


Degree Name

Doctor of Philosophy in Pharmaceutical Sciences


Biomedical and Pharmaceutical Sciences

First Advisor

Ami Vyas


Breast cancer is the second most common cancer among women in the United States (US) with 297,790 new cases expected in 2023. Survival rates for breast cancer have significantly improved over the past decade due to effective screening, diagnosis, and advancement in multimodal therapy, including surgery, radiotherapy, and chemotherapy. In the US, the treatment cost for breast cancer increased substantially from $16.5 billion in 2010 to $23.8 billion in 2020. Moreover, in the US, female breast cancer contributes to 14% of all cancer treatment costs.

Unnecessary use of certain oncology services increases the cost of cancer care without improving the quality and value of cancer care. In April 2012, the American Board of Internal Medicine (ABIM) Foundation launched a national campaign, “Choosing Wisely (CW)” to reduce the use of medical services that do not improve patient’s health. CW is a clinician-led campaign that began in the US but quickly spread to Canada, Australia, Japan, and most parts of Europe. As a part of the CW campaign, the American Society of Clinical Oncology (ASCO) issued the top five measures in 2012 to identify the areas of low-value utilization to promote cost reductions. Later, on October 29, 2013, ASCO issued another set of five measures, including the one focused on chemotherapy-induced nausea vomiting (CINV) and antiemetic use stating: “Don’t give patients starting on a chemotherapy regimen that has low or moderate risk of nausea and vomiting antiemetic drugs intended for use with a regimen that has a high risk of causing nausea and vomiting”.

While chemotherapy has contributed substantially to improved health outcomes, certain chemotherapy regimens are associated with severe nausea and vomiting. Antiemetic prophylaxis is an effective treatment to prevent CINV in the majority of cancer patients. The main prophylactic antiemetics classes include corticosteroids, serotonin receptor antagonists (5HT3-RAs), and Neurokinin-1 receptor antagonists (NK1-RAs). NK1-RAs are clinically efficacious as evident from the clinical trials and were thus rapidly incorporated into antiemetic guidelines for CINV prophylaxis for patients who receive high emetogenic chemotherapy.

To promote the appropriate use of antiemetics, several oncology organizations worldwide have developed clinical guidelines. In the US, these antiemesis guidelines published by ASCO and the National Comprehensive Cancer Network (NCCN) have categorized chemotherapy agents based on their emetogenic potential (high, moderate, or low risk). Both guidelines recommend against using NK1-RAs for low and moderate emetogenic chemotherapy regimens, particularly because these antiemetics are expensive and may not provide any additional benefit. However, adherence to antiemetic guidelines has been suboptimal. Certain low-value oncology services including supportive medications in oncology are being overused when not necessary, thereby increasing the cost of care. ASCO’s CW recommendation is a key step towards curbing inappropriate use of these antiemetics, which could result in reduced health care costs when implemented.

Previous studies conducted in ex-US countries measured antiemetic overuse at the patient level and the estimated overuse rates ranged from 24% to 70% across studies. Little is known about the use of prophylactic antiemetics among patients who receive low to moderate emetic risk chemotherapy. At the time of this writing, only one study has examined the use of prophylactic antiemetic drugs in a US setting. To address this gap in the literature, we assessed the impact of CW on prophylactic NK1-RA use, identified its predictors, and examined whether NK1-RA use is associated with additional costs among minimal, low, and moderate emetogenic groups in patients with breast cancer.

All three objectives of this study were conducted using Optum’s de-identified Clinformatics® Data Mart Database for years 2010 to 2018 (manuscript 1) and years 2013 to 2018 (manuscripts 2 and 3). Optum is a deidentified claims data of beneficiaries of commercial and Medicare Advantage health insurance plans throughout the US.

Manuscript 1: The objective of this study was to examine whether the use of prophylactic NK1-RAs has decreased after ASCO’s CW recommendation (post-CW period). Women aged ≥18 years with invasive breast cancer who initiated low or minimal or moderate emetic risk chemotherapy between January 1, 2011, to November 30, 2018 (n = 25,549). In this retrospective cohort study, interrupted time series (ITS) analysis using segmented regression was conducted to assess the impact of CW antiemetic recommendation on prophylactic NK1-RA use. The unit of analysis was quarterly data (Q1 2011 through Q3 2018). In the entire study cohort, about 8.5% of the women received NK1-RA as prophylaxis. The prophylactic use of NK1-RAs in the pre-CW (2011 to 2013) was 11.1% and 7.7% post-CW (2014 to 2018), which indicates an absolute decrease of 3.4%. In the pre-CW period, there was a quarter-to-quarter increase of 0.11 per 100 patients per quarter. This was followed by an immediate and significant decrease in the prophylactic NK1-RA use by 1.03 per 100 patients in Q2 2014. Furthermore, for the time after CW, we found a significant decline in NK1-RA use by 0.37 per 100 patients per quarter in the post-CW period compared to the pre-CW period This study highlights that there was a significant but modest decline in the use of prophylactic NK1-RAs in the post-CW period.

Manuscript 2: A retrospective cohort study was conducted to identify predictors of prophylactic NK1-RA use during the post-CW period (2013 to 2018). Findings from this study will help understand unnecessary use of NK1-RAs among certain groups This study included women aged 18 years and older with at least one newly initiated claim for minimal/low/moderate emetic risk chemotherapy between January 1, 2014, and November 30, 2018. Descriptive statistics were conducted to describe study cohort characteristics between those who received NK1-RA and those patients who did not use NK1-RAs. A multivariable logistic regression model was used to identify patient’s demographic, socioeconomic, clinical, and environmental characteristics that are associated with prophylactic NK1-RA use. In the post-CW period (n = 18,515), 7.7% of women received prophylactic NK1-RAs. Young women (Adjusted Odds Ratio (AOR)= 2.84; 95% confidence interval (CI) = 2.11 to 3.83 for the 18 to 49 age group), Black race (AOR = 1.35; 95%CI = 1.12 to 1.63), living in the South region (AOR = 1.30; 95%CI = 1.06 to 1.57), with zero comorbidities (AOR = 1.20; 95%CI = 1.02 to 1.41), and at least one mental health condition (AOR = 1.31; 95%CI = 1.13 to 1.50) had higher odds of receiving NK1-RA as antiemetic prophylaxis. Patients who received low emetic risk IV chemotherapy were four times more likely to use NK1-RAs for prophylaxis when compared to those who received IV moderate-risk chemotherapy (AOR = 3.94; 95%CI =3.16 to 4.91). To summarize, prophylactic NK1-RA use was driven by patient-related factors age, region, race/ethnicity, comorbidities, insurance, and emetic risk.

Manuscript 3: The purpose of this study was to assess differences in mean total costs reimbursed by third-party payers and patient out-of-pocket (OOP) costs between those who received prophylactic NK1-RAs compared to other antiemetics during the post-CW period (2013-2018). This retrospective cohort study focused only on NK1-RAs as they are the most expensive antiemetic drug class. We included women aged ≥ 18 years with breast cancer who had at least one claim for minimal, low, or moderate emetic risk chemotherapy. A generalized linear model (GLM) and a two-part model with gamma distribution and log link were used to model mean total third-party and OOP costs, respectively, controlling for baseline patient sociodemographic characteristics. The parameter estimates obtained from the GLM model were exponentiated to obtain a percentage lower costs for prophylactic NK1-RA use and other antiemetics. The analytic cohort comprised a total of 12,068 women. 11.2% received NK1-RAs with or without other antiemetic therapy, 64.8% received first-generation 5HT3RAs with or without steroids, 2.6% received second-generation 5HT3-RAs with or without steroids, 4.5% received steroids only, and 16.8% received a combination of first and second generation 5HT3-RAs with or without steroids. In the adjusted analysis, after accounting for covariates, the mean total third-party payer costs for women who received steroids only, first-generation 5HT3-RAs with or without steroids, or second-generation 5HT3-RAs with or without steroids were found to be significantly lower by 97.8% (p < 0.0001), 95.0% (p < 0.0001) and 42.1% (p = 0.023), respectively when compared to those who received NK1-RAs. The mean OOP costs were higher for those who received prophylactic NK1-RAs ($30; 95% CI = $27 to $32) followed by those who received second-generation 5HT3-RAs with or without steroids ($15; 95%CI = $11 to $18).

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Available for download on Thursday, January 22, 2026