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Oral anticancer and supportive care agents administered to cancer patients are costly and are associated with large copayment requirements or are often not fully reimbursed by private health insurers or Medicare.1 To facilitate access to oral medications, pharmaceutical manufacturers have developed patient assistance programs (PAPs) that provide selected oral medications at no or reduced cost to financially eligible patients. Eligibility criteria, application processes, and program administration for PAPs differ by manufacturer and by product, which can ultimately present logistical barriers.2–4 A systematic review of PAPs found improvements in disease indicator outcomes for patients with common chronic diseases who access these programs.5 However, knowledge about the use of PAPs among cancer patients is limited.6
The University of Texas MD Anderson Cancer Center (MDACC), the largest tertiary care cancer center in the country, has developed a systematic approach to administering a large number of PAPs. In 1996, the MDACC established an institutional program staffed by hospital pharmacy personnel, who navigate cancer patients through PAPs in inpatient and outpatient settings. This program removes the operational and administrative barriers often experienced by patients in smaller clinical settings.
Cancer patients eligible for PAPs at MDACC include those who are uninsured, those who are underinsured, those whose pharmacy benefit limits have been reached, and those whose private health or government insurance has denied coverage of certain oral medications. For example, the Texas Medicaid program limits its low-income beneficiaries to three prescriptions per month, which may lead some of them, particularly those with cancer, to require additional medication assistance through PAPs. As of April 2008, this institutional program established formal relationships with 29 pharmaceutical companies that provide 104 therapeutic or supportive care agents through PAPs to eligible cancer patients in the MDACC outpatient pharmacy.
Methods
Data source
Approval for this study was obtained from the MDACC Institutional Review Board. We conducted a retrospective, secondary analysis of noninvestigational prescription medications from the outpatient pharmacy at MDACC. Data from July 1, 2006, to December 31, 2007, were extracted from computerized pharmacy, medical, and cancer registry databases at MDACC. Prescriptions had to include both patient medical record and social security numbers to validate the patient’s identity as well as the date of pickup to validate that the medication had been dispensed during the study period. When the date of pickup was missing but billing was documented, the date the medication was dispensed was used as the pickup date. All data were de-identified prior to analysis.
PAPs
Prescriptions for oral medications were available to financially eligible individuals via two types of PAPs at MDACC: individual enrollment (60 distinct medications) and bulk drug replacement (44 distinct medications). Individual enrollment required that an eligible patient apply directly to a pharmaceutical company’s PAP for the medication (s) needed. Once approved, the requested medication was mailed directly to the patient or dispensed in the MDACC pharmacy. Given the purpose of this study, we were only interested in those PAP prescription medications dispensed at the outpatient pharmacy.
Bulk replacement PAPs provide available prescription medications in bulk quantities on a monthly (in some cases quarterly) basis to MDACC’s pharmacy to replace medications dispensed to patients who were classified as “indigent” by MDACC-established criteria. Financially indigent patients included those who were Texas residents, uninsured or insured by Medicaid, and not responsible for charges billed to MDACC. All eligible patients could apply for the 60 medications available through individual PAP enrollment, but only indigent patients qualified for the 44 medications available through bulk drug replacement to MDACC.
Patient classifications
Prescription data were extracted from a pharmacy administrative dispensing database; a systematic process was developed to identify case patients (based on financial eligibility) and control patients (similar to case patients with respect to treatments received but were nonusers of PAP programs). Only patients who were potentially eligible for PAPs were included in the study. The case selection was based on MDACC’s determination of a patient’s ability to pay, referred to as credit rating, at the time of a patient’s registration at the institution. Regardless of health insurance status, patients who had a low credit rating (responsible for 0%– 50% of their charges) were classified as being potentially eligible for PAPs. Patients with low credit ratings also included those who were indigent. The control selection identified a set of insured patients, including those with high credit ratings (responsible for 100% of their charges), who had been referred for special financial assistance to obtain specific medications through PAPs.
To be included in the study, patients identified based on a low credit rating had to receive at least 1 of the 104 medications through a PAP to be classified as a PAP user; these patients could receive other medications through traditional payment. PAP nonusers had to receive at least 1 of the 104 medications associated with PAPs through traditional payment or other third-party source, not through a PAP. Patients who had been referred for special assistance had to receive one or more of the PAP medications initially requested from a PAP.
For a drug to be verified as a PAP prescription medication, the pharmacy record could not have documentation of third-party payer or patient payment for that medication. The only exception made for payer and patient payment was for prescription medications provided by one particular pharmaceutical company, which required a $10 copayment for its PAP medications. Once PAP and non-PAP prescriptions were verified, they were aggregated by a unique patient identifier to yield prescriptionuse data for individual patients who were categorized as PAP users versus PAP nonusers.
Patient characteristics
Data on patient gender, race/ethnicity, age, insurance status, and primary cancer site were extracted. Race/ ethnicity was categorized as white, black, Hispanic, or Asian/other. Age was calculated as of July 1, 2006, from the patient’s birth date. Insurance status was based on the patient’s insurance status at the time of registration at MDACC and categorized as follows: no insurance (include self-payers and patients referred from the county public hospital), Medicare, Medicaid, or any of a variety of private/commercial insurances. Private insurances were combined into one category. Information on each patient’s primary cancer site was categorized as blood, breast, genitourinary, head and neck, or other (primarily brain, central nervous system, and an unknown primary site).
The gender and insurance variables had some missing data. When there were conflicting data for a particular patient’s gender, we coded gender as missing. When the insurance type was missing, data on the patient’s insurance status at the time of registration at MDACC were retrieved from MDACC’s financial department.
Prescription medication fills
Data on the prescription medication name (generic or brand) and institutional billing charges per fill were extracted from pharmacy records. Prescriptions were aggregated by generic and brand names, regardless of strength, dosage form, or method of administration, to identify the 20 most frequently dispensed medications overall and for the treatment of cancer. We then used Rxlist.com (www.rxlist.com), an online medication reference program, to identify each medication’s clinical indication(s). For example, the brand name medication Zofran would be aggregated with its generic, ondansetron, and would be considered as one medication indicated for nausea and vomiting.
We extracted patient billing charge per medication fill in dollars by the date of pickup in the outpatient pharmacy. Patient billing charge included patient copayments and did not include any payments from the patient’s payer or health plan. If the billing charge was missing for a medication fill, we applied a comparable charge from a prescription medication of the same name, dosage, quantity, date of pickup, and patient insurance status. When quantity, date, or patient insurance status differed, the lowest available charge was used. All charges were adjusted to the year 2008 using the US Bureau of Labor’s Annual Producer Price Index for pharmaceutical preparation and manufacturing.7
Data analysis
For patient-level analyses, a PAP user was a patient who received at least one medication through a PAP during the study period. We used descriptive statistics to compare patient characteristics of PAP users versus PAP nonusers. Next, we conducted separate unadjusted binary logit regression analyses (interpreted with odds ratios [ORs] and 95% confidence intervals [CIs]) to estimate the differences in the probability of being a PAP user for each of the patient characteristics. All patient characteristics that were statistically significant at P < 0.20 for the unadjusted analyses8 were included in the final multivariable model. The a priori level of significance was set at P < 0.05 for the multivariable model.
For other analyses conducted at the prescription level, a PAP medication was a medication verified as being provided through a PAP. We used descriptive statistics to compare the 20 most frequently dispensed prescription medications (overall and for anticancer agents specifically) by PAP status and clinical indication. Analyses were conducted in Microsoft Excel and STATA Version 11.9
Results
Study patients and prescription medications
During the 18-month observation period, a monthly mean of 1,550 patients received a monthly total of 19,000 noninvestigational medications in the outpatient pharmacy. Of these patients, 7.5% (n = 1,929) met study eligibility criteria for PAPs and received 1 of the 104 medications provided through PAPs. Thus, there were 979 PAP users and 950 PAP nonusers in the final study population. In total, the study population received 23.3% (n = 77,592) of all outpatient medications administered during this period, of which anticancer agents represented 4% (n = 3,105; Table 1).
Comparison of patient characteristics
In comparison to PAP nonusers, PAP users were, on average, younger (48 vs 52 years), indigent (73% vs 19%), white (50% vs 43%), and covered by Medicaid or were uninsured (75% versus 20%). PAP users also had more prescriptions fills (median = 30 vs 20) during the study period at the institution. Univariate analyses showed that all patient characteristics, except gender, significantly predicted PAP use. Given the strong correlation of indigent and insurance status to PAP use, we conducted post hoc analyses to assess the potential for multicollinearity between the two patient characteristics. The variance inflation factor (VIF = 4.57) did not indicate multicollinearity concerns.
In the adjusted model, patients who were indigent (OR = 16.95; 95% CI: 6.845, 41.960), uninsured (OR = 4.60; 95% CI: 2.118, 9.970), and under the age of 65 years (OR = 2.31; 95% CI: 1.517, 3.509) were 2- to 17- fold more likely than others to be PAP users. Black patients were 31% (P = 0.020) less likely to access PAPs than were white patients.
Overall prescription medication fills The top-20 prescription medication fills from the MDACC outpatient pharmacy differed by PAP user group and PAP status. For PAP users, 88% of the most common medications obtained from PAPs were supportive care agents, including treatments of bacterial infections (n =887 fills; 49/month), antiemetics (n = 492 fills; 27/month), and gastroesophageal reflux disease (n = 492 fills; 27/month). Conversely, treatments for neutropenia and anticoagulation represented nearly half ($1.8 million) of the total charges avoided through PAPs to PAP users ($3.9 million). The most common medications not obtained from PAPs were for treatment of pain (PAP users = 292 fills/month, nonusers = 218 fills/month), versus only 13 fills/ month for pain medications from PAPs. Medications indicated to treat pain and nausea/vomiting accounted for the largest proportion of charges for medications not filled by PAPs for both PAP users and nonusers.
Anticancer agent prescription fills
For both PAP users and nonusers, the top-20 anticancer oral agent fills represented 93% (n = 2,892 of 3,105) of all anticancer oral fills (Table 6), with 16% (n = 454) of these oral fills being provided through PAPs. Among PAP users, anticancer agents from PAPs accounted for 40% of their total charges and 35% of the total number of agents. Temozolomide (Temodar; mean charge/fill = $3,346) represented the highest amount of total charges ($220,857) from PAPs, whereas imatinib (Gleevec; mean charge/fill = $5,372) and dasatinib (Sprycel; mean charge/fill = $5,221) accounted for the highest average charges per fill. Anastrozole (Arimidex; n = 178 fills; 10/month), capecitabine (Xeloda; n = 91 fills; 5/month), and temozolomide (n = 66 fills; 4/month) accounted for 70% of agents from PAPs. PAP users who were given bicalutamide received 100% of those agents from PAPs. Five of the seven oral anticancer agents with no fills from PAPs had initial US Food and Drug Administration approval years before 2000.
Discussion
At MDACC, PAPs are designed to help cancer patients overcome financial barriers to accessing oral supportive and anticancer agents. Over an 18-month observation period, less than 5% of the cancer patients at MDACC who received prescription medications from the outpatient pharmacy were enrolled in a PAP— and these PAPs provided 13% of their medication fills, representing an annualized $3.6 million in pharmaceutical expenditures. In interpreting our findings, several factors should be considered.
Oral anticancer agents accounted for 4% of all prescription medication fills during the study period. Comparatively, an analysis of the 2007 National Ambulatory Medical Care Survey showed that less than 1% of cancer patients were prescribed at least one oral anticancer agent.10 This finding indicates that both nationally and at MDACC, chemotherapy continues to be largely provided parenterally, as there is more of a financial benefit from intravenous therapies that are often reimbursed by insurers as well as PAPs.
In the outpatient pharmacy at MDACC, PAPs provided nearly onethird of oral anticancer fills for PAP users—totaling a mean of $500,000 per month in expenditures. However, three agents, anastrozole (for breast cancer), capecitabine (for breast and GI cancers, primarily), and temozolomide (for brain tumors) accounted for 75% of all of the anticancer agents provided by PAPs. We also found that pharmaceutical companies provided expensive newer, targeted, anticancer agents (primarily dasatinib and imatinib, the two agents with the greatest pharmaceutical per-person expenditures by the PAP program) through PAPs.
Although PAPs filled a strong and focused need for a small number of oral chemotherapy agents for some individuals with breast, GI, and brain cancers, they did not provide much benefit for a wide range of supportive care agents, particularly those that are schedule C and are used to treatcancer pain. Pain is the most prevalent symptom reported by cancer patients, 11 but there were few schedule C pain medications among the most common medications provided through PAPs. These substances are generally not provided by PAPs because of legal and substance abuse concerns.12 However, these medications were commonly prescribed to PAP users and PAP nonusers alike, outside of the PAP program. It would be important to evaluate the comparative success in treating pain among cancer patients at MDACC who receive a limited array of pain medications from PAPs (usually agents that are not substance-controlled by the Drug Enforcement Administration) versus treatment of pain experienced by patients whose medications are not reimbursed by PAPs.
We found that being younger than 65 years old, being indigent, and having no health insurance were the strongest predictors of using a PAP. This finding was expected, given that US adults younger than age 65 are ineligible for outpatient prescription medication coverage through Medicare Part D. However, contrary to expectations, about 45% of PAP users had either private or governmentsupplied health insurance. Because it is not uncommon for cancer patients to endure economic hardship (including bankruptcy) when trying to finance their care,13 healthcare professionals could recommend PAPs and other relevant assistance programs to all of their cancer patients.
With the expansion of health insurance through the Patient Protection and Affordable Health Care Act of 2010, it is hoped that the need for cancer patients to enroll in PAPs will be diminished; yet, given the reality of the high cost of anticancer agents, reimbursement policies for these agents, and tiered formularies among insurers leading to high outof- pocket costs for patients, the need for PAPs is likely to remain. PAPs can be a viable option for some patients, but healthcare professionals should be aware that there are a number of concerns about these programs, including their complex and burdensome application process and often limited variety of available drugs.14
This study is not without its limitations. First, we may have underestimated our sample of PAP patients due to the fact that MDACC did not electronically or systematically track the use of PAPs within its pharmacy database at the time of the study. The institution is in the process of developing such a system.
Second, the data used in this study cannot be assumed to reflect a “closed pharmacy” setting because some patients, particularly those who have health insurance with prescription medication coverage, may have received some of their medications from outside pharmacies.
Third, because insurance status is not necessarily a static characteristic, insurance status in this study was classified based on that at the time of registration with MDACC’s financial department, and no account was taken of changes that might have occurred.
Last, our results are not necessarily generalizable to all cancer populations, time periods, or settings. Cancer patients treated in academic centers such as MDACC may differ from those who are treated in community settings. In particular, fewer than 10% of patients at MDACC qualified for indigent financial assistance in 2007,15 which is likely to have impacted the number of patients who were potentially eligible for PAPs. It is also likely that had our study been conducted prior to the implementation of Medicare Part D, our sample of PAP patients would have been older. Nevertheless, our results may be generalizable to cancer patients receiving care in other academic cancer centers.
Conclusion This study builds upon a previous description of implementing PAPs in a comprehensive cancer center16 as well as contributes to our limited knowledge of the use of PAPs among cancer patients.6 Future studies should prospectively examine cancer patients’ experiences and satisfaction with PAPs from the process of applying to the point of receiving requested therapies and evaluate the effect of PAPs on cancer outcomes in various care settings. Multidisciplinary teams, including pharmacists and clinicians, should establish and recommend valid and relevant clinical endpoints for researchers to use in effectiveness studies of PAPs and cancer patients, particularly as they relate to oral anticancer agent use. Given that these oral agents represent more than 25% of cancer therapies in development,17 future studies of PAPs are ideal for evaluating concerns of accessibility, affordability, and compliance related to these agents.
MDACC is a unique resource for observers of PAPs, as it is the largest cancer center in the United States. However, few cancer patients at MDACC were eligible for and accessed PAPs in the outpatient pharmacy. Although smaller cancer centers may not be able to devote the same degree of financial and personnel resources to their patients as does MDACC, these centers could seek to build relationships with specific pharmaceutical companies that provide PAPs for the oral anticancer and supportive care therapies most commonly prescribed and administered at their centers. Scarce resources could also be utilized in other ways, such as by developing public-private risk pools for establishment of indigent care funds.
Acknowledgments: The authors thank Chun Feng, Jason Lau, and Oliver Max for their special assistance; Dr. Phoenix Do for her study design recommendations; and Karyn Popham for her editorial support. They especially thank Rebecca Arbuckle, RPh, for her support of this project. At the time of the study, Dr. Felder was supported by a Predoctoral Fellowship from The University of Texas School of Public Health Cancer Education and Career Development Program, funded by National Cancer Institute/NIH Grant R25-CA-57712-17.
References
1. Hede K. Increase in oral cancer drugs raises thorny issues for oncology practices. J Natl Cancer Inst 2009;101:1534–1536.
2. Chisholm MA, DiPiro JT. Pharmaceutical manufacturer assistance programs. Arch Intern Med 2002;162:780–784.
3. Duke KS, Raube K, Lipton HL. Patientassistance programs: assessment of and use by safety-net clinics. Am J Health Syst Pharm 2005;62:726–731.
4. Pisu M, Richman J, Allison JJ, Williams OD, Kiefe CI. Pharmaceuticals companies’ medication assistance programs: potentially useful but too burdensome to use? South Med J 2009;102:139–144.
5. Felder TM, Palmer NR, Lal LS, Mullen PD. What is the evidence for pharmaceutical patient assistance programs? a systematic review. J Health Care Poor Underserved 2011;22:24–49.
6. Meropol NJ, Schrag D, Smith TJ, et al. American Society of Clinical Oncology guidance statement: the cost of cancer care. J Clin Oncol 2009;27:3868–3874.
7. United States Department of Labor, Bureau of Labor Statistics: Producer Price Index Industry Data—Pharmaceutical Preparation & Manufacturing; 2010 [updated April 26, 2010]. http://www.bls.gov/ppi/data.htm. Accessed June 22, 2011.
8. Hosmer DW, Lemeshow S. Applied Logistic
Logistic
Regression. New York: Wiley; 2000. 9. StataCorp LP. STATA statistical software. 2009; Release 11.
10. Arora S. Use of oral chemotherapeutic medications in non-traditional ambulatory settings; 2009. http://digarchive.library.vcu. edu/dspace/bitstream/10156/2711/1/Thesis_ MPH_sameer.pdf. Accessed June 22, 2011.
11. Cherny NI. The management of cancer pain. CA Cancer J Clin 2000;50:70–116.
12. Williams K. Accessing patient assistance programs to meet clients’ medication needs. J Am Acad Nurse Pract 2000;12:233– 235.
13. National Survey of Households Affected by Cancer: Kaiser Family Foundation; 2006 [updated November 2006]. http://kff.org/kaiserpolls/ upload/7591.pdf. Accessed June 22, 2011.
14. Choudhry NK, Lee JL, Agnew-Blais J, Corcoran C, Shrank WH. Drug company- sponsored patient assistance programs: a viable safety net? Health Aff (Millwood) 2009;28:827–834.
15. Ackerman T. M.D. Anderson submits its records on charitable care: cancer center hopes to quell Iowa senator’s investigation. Houston Chronicle. October 9, 2008. http:// www.chron.com/disp/story.mpl/metropolitan/ 6050254.html. Accessed June 22, 2011.
16. Johnson PE. Patient assistance programs and patient advocacy foundations: alternatives for obtaining prescription medications when insurance fails. Am J Health Syst Pharm 2006;63(21 suppl 7):S13–S17.
17. Weingart SA, Brown E, Bach PB, et al. National Comprehensive Cancer Network task force report: oral chemotherapy. JNCCN 2008;6(suppl 3):S1–S25.
Oral anticancer and supportive care agents administered to cancer patients are costly and are associated with large copayment requirements or are often not fully reimbursed by private health insurers or Medicare.1 To facilitate access to oral medications, pharmaceutical manufacturers have developed patient assistance programs (PAPs) that provide selected oral medications at no or reduced cost to financially eligible patients. Eligibility criteria, application processes, and program administration for PAPs differ by manufacturer and by product, which can ultimately present logistical barriers.2–4 A systematic review of PAPs found improvements in disease indicator outcomes for patients with common chronic diseases who access these programs.5 However, knowledge about the use of PAPs among cancer patients is limited.6
The University of Texas MD Anderson Cancer Center (MDACC), the largest tertiary care cancer center in the country, has developed a systematic approach to administering a large number of PAPs. In 1996, the MDACC established an institutional program staffed by hospital pharmacy personnel, who navigate cancer patients through PAPs in inpatient and outpatient settings. This program removes the operational and administrative barriers often experienced by patients in smaller clinical settings.
Cancer patients eligible for PAPs at MDACC include those who are uninsured, those who are underinsured, those whose pharmacy benefit limits have been reached, and those whose private health or government insurance has denied coverage of certain oral medications. For example, the Texas Medicaid program limits its low-income beneficiaries to three prescriptions per month, which may lead some of them, particularly those with cancer, to require additional medication assistance through PAPs. As of April 2008, this institutional program established formal relationships with 29 pharmaceutical companies that provide 104 therapeutic or supportive care agents through PAPs to eligible cancer patients in the MDACC outpatient pharmacy.
Methods
Data source
Approval for this study was obtained from the MDACC Institutional Review Board. We conducted a retrospective, secondary analysis of noninvestigational prescription medications from the outpatient pharmacy at MDACC. Data from July 1, 2006, to December 31, 2007, were extracted from computerized pharmacy, medical, and cancer registry databases at MDACC. Prescriptions had to include both patient medical record and social security numbers to validate the patient’s identity as well as the date of pickup to validate that the medication had been dispensed during the study period. When the date of pickup was missing but billing was documented, the date the medication was dispensed was used as the pickup date. All data were de-identified prior to analysis.
PAPs
Prescriptions for oral medications were available to financially eligible individuals via two types of PAPs at MDACC: individual enrollment (60 distinct medications) and bulk drug replacement (44 distinct medications). Individual enrollment required that an eligible patient apply directly to a pharmaceutical company’s PAP for the medication (s) needed. Once approved, the requested medication was mailed directly to the patient or dispensed in the MDACC pharmacy. Given the purpose of this study, we were only interested in those PAP prescription medications dispensed at the outpatient pharmacy.
Bulk replacement PAPs provide available prescription medications in bulk quantities on a monthly (in some cases quarterly) basis to MDACC’s pharmacy to replace medications dispensed to patients who were classified as “indigent” by MDACC-established criteria. Financially indigent patients included those who were Texas residents, uninsured or insured by Medicaid, and not responsible for charges billed to MDACC. All eligible patients could apply for the 60 medications available through individual PAP enrollment, but only indigent patients qualified for the 44 medications available through bulk drug replacement to MDACC.
Patient classifications
Prescription data were extracted from a pharmacy administrative dispensing database; a systematic process was developed to identify case patients (based on financial eligibility) and control patients (similar to case patients with respect to treatments received but were nonusers of PAP programs). Only patients who were potentially eligible for PAPs were included in the study. The case selection was based on MDACC’s determination of a patient’s ability to pay, referred to as credit rating, at the time of a patient’s registration at the institution. Regardless of health insurance status, patients who had a low credit rating (responsible for 0%– 50% of their charges) were classified as being potentially eligible for PAPs. Patients with low credit ratings also included those who were indigent. The control selection identified a set of insured patients, including those with high credit ratings (responsible for 100% of their charges), who had been referred for special financial assistance to obtain specific medications through PAPs.
To be included in the study, patients identified based on a low credit rating had to receive at least 1 of the 104 medications through a PAP to be classified as a PAP user; these patients could receive other medications through traditional payment. PAP nonusers had to receive at least 1 of the 104 medications associated with PAPs through traditional payment or other third-party source, not through a PAP. Patients who had been referred for special assistance had to receive one or more of the PAP medications initially requested from a PAP.
For a drug to be verified as a PAP prescription medication, the pharmacy record could not have documentation of third-party payer or patient payment for that medication. The only exception made for payer and patient payment was for prescription medications provided by one particular pharmaceutical company, which required a $10 copayment for its PAP medications. Once PAP and non-PAP prescriptions were verified, they were aggregated by a unique patient identifier to yield prescriptionuse data for individual patients who were categorized as PAP users versus PAP nonusers.
Patient characteristics
Data on patient gender, race/ethnicity, age, insurance status, and primary cancer site were extracted. Race/ ethnicity was categorized as white, black, Hispanic, or Asian/other. Age was calculated as of July 1, 2006, from the patient’s birth date. Insurance status was based on the patient’s insurance status at the time of registration at MDACC and categorized as follows: no insurance (include self-payers and patients referred from the county public hospital), Medicare, Medicaid, or any of a variety of private/commercial insurances. Private insurances were combined into one category. Information on each patient’s primary cancer site was categorized as blood, breast, genitourinary, head and neck, or other (primarily brain, central nervous system, and an unknown primary site).
The gender and insurance variables had some missing data. When there were conflicting data for a particular patient’s gender, we coded gender as missing. When the insurance type was missing, data on the patient’s insurance status at the time of registration at MDACC were retrieved from MDACC’s financial department.
Prescription medication fills
Data on the prescription medication name (generic or brand) and institutional billing charges per fill were extracted from pharmacy records. Prescriptions were aggregated by generic and brand names, regardless of strength, dosage form, or method of administration, to identify the 20 most frequently dispensed medications overall and for the treatment of cancer. We then used Rxlist.com (www.rxlist.com), an online medication reference program, to identify each medication’s clinical indication(s). For example, the brand name medication Zofran would be aggregated with its generic, ondansetron, and would be considered as one medication indicated for nausea and vomiting.
We extracted patient billing charge per medication fill in dollars by the date of pickup in the outpatient pharmacy. Patient billing charge included patient copayments and did not include any payments from the patient’s payer or health plan. If the billing charge was missing for a medication fill, we applied a comparable charge from a prescription medication of the same name, dosage, quantity, date of pickup, and patient insurance status. When quantity, date, or patient insurance status differed, the lowest available charge was used. All charges were adjusted to the year 2008 using the US Bureau of Labor’s Annual Producer Price Index for pharmaceutical preparation and manufacturing.7
Data analysis
For patient-level analyses, a PAP user was a patient who received at least one medication through a PAP during the study period. We used descriptive statistics to compare patient characteristics of PAP users versus PAP nonusers. Next, we conducted separate unadjusted binary logit regression analyses (interpreted with odds ratios [ORs] and 95% confidence intervals [CIs]) to estimate the differences in the probability of being a PAP user for each of the patient characteristics. All patient characteristics that were statistically significant at P < 0.20 for the unadjusted analyses8 were included in the final multivariable model. The a priori level of significance was set at P < 0.05 for the multivariable model.
For other analyses conducted at the prescription level, a PAP medication was a medication verified as being provided through a PAP. We used descriptive statistics to compare the 20 most frequently dispensed prescription medications (overall and for anticancer agents specifically) by PAP status and clinical indication. Analyses were conducted in Microsoft Excel and STATA Version 11.9
Results
Study patients and prescription medications
During the 18-month observation period, a monthly mean of 1,550 patients received a monthly total of 19,000 noninvestigational medications in the outpatient pharmacy. Of these patients, 7.5% (n = 1,929) met study eligibility criteria for PAPs and received 1 of the 104 medications provided through PAPs. Thus, there were 979 PAP users and 950 PAP nonusers in the final study population. In total, the study population received 23.3% (n = 77,592) of all outpatient medications administered during this period, of which anticancer agents represented 4% (n = 3,105; Table 1).
Comparison of patient characteristics
In comparison to PAP nonusers, PAP users were, on average, younger (48 vs 52 years), indigent (73% vs 19%), white (50% vs 43%), and covered by Medicaid or were uninsured (75% versus 20%). PAP users also had more prescriptions fills (median = 30 vs 20) during the study period at the institution. Univariate analyses showed that all patient characteristics, except gender, significantly predicted PAP use. Given the strong correlation of indigent and insurance status to PAP use, we conducted post hoc analyses to assess the potential for multicollinearity between the two patient characteristics. The variance inflation factor (VIF = 4.57) did not indicate multicollinearity concerns.
In the adjusted model, patients who were indigent (OR = 16.95; 95% CI: 6.845, 41.960), uninsured (OR = 4.60; 95% CI: 2.118, 9.970), and under the age of 65 years (OR = 2.31; 95% CI: 1.517, 3.509) were 2- to 17- fold more likely than others to be PAP users. Black patients were 31% (P = 0.020) less likely to access PAPs than were white patients.
Overall prescription medication fills The top-20 prescription medication fills from the MDACC outpatient pharmacy differed by PAP user group and PAP status. For PAP users, 88% of the most common medications obtained from PAPs were supportive care agents, including treatments of bacterial infections (n =887 fills; 49/month), antiemetics (n = 492 fills; 27/month), and gastroesophageal reflux disease (n = 492 fills; 27/month). Conversely, treatments for neutropenia and anticoagulation represented nearly half ($1.8 million) of the total charges avoided through PAPs to PAP users ($3.9 million). The most common medications not obtained from PAPs were for treatment of pain (PAP users = 292 fills/month, nonusers = 218 fills/month), versus only 13 fills/ month for pain medications from PAPs. Medications indicated to treat pain and nausea/vomiting accounted for the largest proportion of charges for medications not filled by PAPs for both PAP users and nonusers.
Anticancer agent prescription fills
For both PAP users and nonusers, the top-20 anticancer oral agent fills represented 93% (n = 2,892 of 3,105) of all anticancer oral fills (Table 6), with 16% (n = 454) of these oral fills being provided through PAPs. Among PAP users, anticancer agents from PAPs accounted for 40% of their total charges and 35% of the total number of agents. Temozolomide (Temodar; mean charge/fill = $3,346) represented the highest amount of total charges ($220,857) from PAPs, whereas imatinib (Gleevec; mean charge/fill = $5,372) and dasatinib (Sprycel; mean charge/fill = $5,221) accounted for the highest average charges per fill. Anastrozole (Arimidex; n = 178 fills; 10/month), capecitabine (Xeloda; n = 91 fills; 5/month), and temozolomide (n = 66 fills; 4/month) accounted for 70% of agents from PAPs. PAP users who were given bicalutamide received 100% of those agents from PAPs. Five of the seven oral anticancer agents with no fills from PAPs had initial US Food and Drug Administration approval years before 2000.
Discussion
At MDACC, PAPs are designed to help cancer patients overcome financial barriers to accessing oral supportive and anticancer agents. Over an 18-month observation period, less than 5% of the cancer patients at MDACC who received prescription medications from the outpatient pharmacy were enrolled in a PAP— and these PAPs provided 13% of their medication fills, representing an annualized $3.6 million in pharmaceutical expenditures. In interpreting our findings, several factors should be considered.
Oral anticancer agents accounted for 4% of all prescription medication fills during the study period. Comparatively, an analysis of the 2007 National Ambulatory Medical Care Survey showed that less than 1% of cancer patients were prescribed at least one oral anticancer agent.10 This finding indicates that both nationally and at MDACC, chemotherapy continues to be largely provided parenterally, as there is more of a financial benefit from intravenous therapies that are often reimbursed by insurers as well as PAPs.
In the outpatient pharmacy at MDACC, PAPs provided nearly onethird of oral anticancer fills for PAP users—totaling a mean of $500,000 per month in expenditures. However, three agents, anastrozole (for breast cancer), capecitabine (for breast and GI cancers, primarily), and temozolomide (for brain tumors) accounted for 75% of all of the anticancer agents provided by PAPs. We also found that pharmaceutical companies provided expensive newer, targeted, anticancer agents (primarily dasatinib and imatinib, the two agents with the greatest pharmaceutical per-person expenditures by the PAP program) through PAPs.
Although PAPs filled a strong and focused need for a small number of oral chemotherapy agents for some individuals with breast, GI, and brain cancers, they did not provide much benefit for a wide range of supportive care agents, particularly those that are schedule C and are used to treatcancer pain. Pain is the most prevalent symptom reported by cancer patients, 11 but there were few schedule C pain medications among the most common medications provided through PAPs. These substances are generally not provided by PAPs because of legal and substance abuse concerns.12 However, these medications were commonly prescribed to PAP users and PAP nonusers alike, outside of the PAP program. It would be important to evaluate the comparative success in treating pain among cancer patients at MDACC who receive a limited array of pain medications from PAPs (usually agents that are not substance-controlled by the Drug Enforcement Administration) versus treatment of pain experienced by patients whose medications are not reimbursed by PAPs.
We found that being younger than 65 years old, being indigent, and having no health insurance were the strongest predictors of using a PAP. This finding was expected, given that US adults younger than age 65 are ineligible for outpatient prescription medication coverage through Medicare Part D. However, contrary to expectations, about 45% of PAP users had either private or governmentsupplied health insurance. Because it is not uncommon for cancer patients to endure economic hardship (including bankruptcy) when trying to finance their care,13 healthcare professionals could recommend PAPs and other relevant assistance programs to all of their cancer patients.
With the expansion of health insurance through the Patient Protection and Affordable Health Care Act of 2010, it is hoped that the need for cancer patients to enroll in PAPs will be diminished; yet, given the reality of the high cost of anticancer agents, reimbursement policies for these agents, and tiered formularies among insurers leading to high outof- pocket costs for patients, the need for PAPs is likely to remain. PAPs can be a viable option for some patients, but healthcare professionals should be aware that there are a number of concerns about these programs, including their complex and burdensome application process and often limited variety of available drugs.14
This study is not without its limitations. First, we may have underestimated our sample of PAP patients due to the fact that MDACC did not electronically or systematically track the use of PAPs within its pharmacy database at the time of the study. The institution is in the process of developing such a system.
Second, the data used in this study cannot be assumed to reflect a “closed pharmacy” setting because some patients, particularly those who have health insurance with prescription medication coverage, may have received some of their medications from outside pharmacies.
Third, because insurance status is not necessarily a static characteristic, insurance status in this study was classified based on that at the time of registration with MDACC’s financial department, and no account was taken of changes that might have occurred.
Last, our results are not necessarily generalizable to all cancer populations, time periods, or settings. Cancer patients treated in academic centers such as MDACC may differ from those who are treated in community settings. In particular, fewer than 10% of patients at MDACC qualified for indigent financial assistance in 2007,15 which is likely to have impacted the number of patients who were potentially eligible for PAPs. It is also likely that had our study been conducted prior to the implementation of Medicare Part D, our sample of PAP patients would have been older. Nevertheless, our results may be generalizable to cancer patients receiving care in other academic cancer centers.
Conclusion This study builds upon a previous description of implementing PAPs in a comprehensive cancer center16 as well as contributes to our limited knowledge of the use of PAPs among cancer patients.6 Future studies should prospectively examine cancer patients’ experiences and satisfaction with PAPs from the process of applying to the point of receiving requested therapies and evaluate the effect of PAPs on cancer outcomes in various care settings. Multidisciplinary teams, including pharmacists and clinicians, should establish and recommend valid and relevant clinical endpoints for researchers to use in effectiveness studies of PAPs and cancer patients, particularly as they relate to oral anticancer agent use. Given that these oral agents represent more than 25% of cancer therapies in development,17 future studies of PAPs are ideal for evaluating concerns of accessibility, affordability, and compliance related to these agents.
MDACC is a unique resource for observers of PAPs, as it is the largest cancer center in the United States. However, few cancer patients at MDACC were eligible for and accessed PAPs in the outpatient pharmacy. Although smaller cancer centers may not be able to devote the same degree of financial and personnel resources to their patients as does MDACC, these centers could seek to build relationships with specific pharmaceutical companies that provide PAPs for the oral anticancer and supportive care therapies most commonly prescribed and administered at their centers. Scarce resources could also be utilized in other ways, such as by developing public-private risk pools for establishment of indigent care funds.
Acknowledgments: The authors thank Chun Feng, Jason Lau, and Oliver Max for their special assistance; Dr. Phoenix Do for her study design recommendations; and Karyn Popham for her editorial support. They especially thank Rebecca Arbuckle, RPh, for her support of this project. At the time of the study, Dr. Felder was supported by a Predoctoral Fellowship from The University of Texas School of Public Health Cancer Education and Career Development Program, funded by National Cancer Institute/NIH Grant R25-CA-57712-17.
References
1. Hede K. Increase in oral cancer drugs raises thorny issues for oncology practices. J Natl Cancer Inst 2009;101:1534–1536.
2. Chisholm MA, DiPiro JT. Pharmaceutical manufacturer assistance programs. Arch Intern Med 2002;162:780–784.
3. Duke KS, Raube K, Lipton HL. Patientassistance programs: assessment of and use by safety-net clinics. Am J Health Syst Pharm 2005;62:726–731.
4. Pisu M, Richman J, Allison JJ, Williams OD, Kiefe CI. Pharmaceuticals companies’ medication assistance programs: potentially useful but too burdensome to use? South Med J 2009;102:139–144.
5. Felder TM, Palmer NR, Lal LS, Mullen PD. What is the evidence for pharmaceutical patient assistance programs? a systematic review. J Health Care Poor Underserved 2011;22:24–49.
6. Meropol NJ, Schrag D, Smith TJ, et al. American Society of Clinical Oncology guidance statement: the cost of cancer care. J Clin Oncol 2009;27:3868–3874.
7. United States Department of Labor, Bureau of Labor Statistics: Producer Price Index Industry Data—Pharmaceutical Preparation & Manufacturing; 2010 [updated April 26, 2010]. http://www.bls.gov/ppi/data.htm. Accessed June 22, 2011.
8. Hosmer DW, Lemeshow S. Applied Logistic
Logistic
Regression. New York: Wiley; 2000. 9. StataCorp LP. STATA statistical software. 2009; Release 11.
10. Arora S. Use of oral chemotherapeutic medications in non-traditional ambulatory settings; 2009. http://digarchive.library.vcu. edu/dspace/bitstream/10156/2711/1/Thesis_ MPH_sameer.pdf. Accessed June 22, 2011.
11. Cherny NI. The management of cancer pain. CA Cancer J Clin 2000;50:70–116.
12. Williams K. Accessing patient assistance programs to meet clients’ medication needs. J Am Acad Nurse Pract 2000;12:233– 235.
13. National Survey of Households Affected by Cancer: Kaiser Family Foundation; 2006 [updated November 2006]. http://kff.org/kaiserpolls/ upload/7591.pdf. Accessed June 22, 2011.
14. Choudhry NK, Lee JL, Agnew-Blais J, Corcoran C, Shrank WH. Drug company- sponsored patient assistance programs: a viable safety net? Health Aff (Millwood) 2009;28:827–834.
15. Ackerman T. M.D. Anderson submits its records on charitable care: cancer center hopes to quell Iowa senator’s investigation. Houston Chronicle. October 9, 2008. http:// www.chron.com/disp/story.mpl/metropolitan/ 6050254.html. Accessed June 22, 2011.
16. Johnson PE. Patient assistance programs and patient advocacy foundations: alternatives for obtaining prescription medications when insurance fails. Am J Health Syst Pharm 2006;63(21 suppl 7):S13–S17.
17. Weingart SA, Brown E, Bach PB, et al. National Comprehensive Cancer Network task force report: oral chemotherapy. JNCCN 2008;6(suppl 3):S1–S25.
Oral anticancer and supportive care agents administered to cancer patients are costly and are associated with large copayment requirements or are often not fully reimbursed by private health insurers or Medicare.1 To facilitate access to oral medications, pharmaceutical manufacturers have developed patient assistance programs (PAPs) that provide selected oral medications at no or reduced cost to financially eligible patients. Eligibility criteria, application processes, and program administration for PAPs differ by manufacturer and by product, which can ultimately present logistical barriers.2–4 A systematic review of PAPs found improvements in disease indicator outcomes for patients with common chronic diseases who access these programs.5 However, knowledge about the use of PAPs among cancer patients is limited.6
The University of Texas MD Anderson Cancer Center (MDACC), the largest tertiary care cancer center in the country, has developed a systematic approach to administering a large number of PAPs. In 1996, the MDACC established an institutional program staffed by hospital pharmacy personnel, who navigate cancer patients through PAPs in inpatient and outpatient settings. This program removes the operational and administrative barriers often experienced by patients in smaller clinical settings.
Cancer patients eligible for PAPs at MDACC include those who are uninsured, those who are underinsured, those whose pharmacy benefit limits have been reached, and those whose private health or government insurance has denied coverage of certain oral medications. For example, the Texas Medicaid program limits its low-income beneficiaries to three prescriptions per month, which may lead some of them, particularly those with cancer, to require additional medication assistance through PAPs. As of April 2008, this institutional program established formal relationships with 29 pharmaceutical companies that provide 104 therapeutic or supportive care agents through PAPs to eligible cancer patients in the MDACC outpatient pharmacy.
Methods
Data source
Approval for this study was obtained from the MDACC Institutional Review Board. We conducted a retrospective, secondary analysis of noninvestigational prescription medications from the outpatient pharmacy at MDACC. Data from July 1, 2006, to December 31, 2007, were extracted from computerized pharmacy, medical, and cancer registry databases at MDACC. Prescriptions had to include both patient medical record and social security numbers to validate the patient’s identity as well as the date of pickup to validate that the medication had been dispensed during the study period. When the date of pickup was missing but billing was documented, the date the medication was dispensed was used as the pickup date. All data were de-identified prior to analysis.
PAPs
Prescriptions for oral medications were available to financially eligible individuals via two types of PAPs at MDACC: individual enrollment (60 distinct medications) and bulk drug replacement (44 distinct medications). Individual enrollment required that an eligible patient apply directly to a pharmaceutical company’s PAP for the medication (s) needed. Once approved, the requested medication was mailed directly to the patient or dispensed in the MDACC pharmacy. Given the purpose of this study, we were only interested in those PAP prescription medications dispensed at the outpatient pharmacy.
Bulk replacement PAPs provide available prescription medications in bulk quantities on a monthly (in some cases quarterly) basis to MDACC’s pharmacy to replace medications dispensed to patients who were classified as “indigent” by MDACC-established criteria. Financially indigent patients included those who were Texas residents, uninsured or insured by Medicaid, and not responsible for charges billed to MDACC. All eligible patients could apply for the 60 medications available through individual PAP enrollment, but only indigent patients qualified for the 44 medications available through bulk drug replacement to MDACC.
Patient classifications
Prescription data were extracted from a pharmacy administrative dispensing database; a systematic process was developed to identify case patients (based on financial eligibility) and control patients (similar to case patients with respect to treatments received but were nonusers of PAP programs). Only patients who were potentially eligible for PAPs were included in the study. The case selection was based on MDACC’s determination of a patient’s ability to pay, referred to as credit rating, at the time of a patient’s registration at the institution. Regardless of health insurance status, patients who had a low credit rating (responsible for 0%– 50% of their charges) were classified as being potentially eligible for PAPs. Patients with low credit ratings also included those who were indigent. The control selection identified a set of insured patients, including those with high credit ratings (responsible for 100% of their charges), who had been referred for special financial assistance to obtain specific medications through PAPs.
To be included in the study, patients identified based on a low credit rating had to receive at least 1 of the 104 medications through a PAP to be classified as a PAP user; these patients could receive other medications through traditional payment. PAP nonusers had to receive at least 1 of the 104 medications associated with PAPs through traditional payment or other third-party source, not through a PAP. Patients who had been referred for special assistance had to receive one or more of the PAP medications initially requested from a PAP.
For a drug to be verified as a PAP prescription medication, the pharmacy record could not have documentation of third-party payer or patient payment for that medication. The only exception made for payer and patient payment was for prescription medications provided by one particular pharmaceutical company, which required a $10 copayment for its PAP medications. Once PAP and non-PAP prescriptions were verified, they were aggregated by a unique patient identifier to yield prescriptionuse data for individual patients who were categorized as PAP users versus PAP nonusers.
Patient characteristics
Data on patient gender, race/ethnicity, age, insurance status, and primary cancer site were extracted. Race/ ethnicity was categorized as white, black, Hispanic, or Asian/other. Age was calculated as of July 1, 2006, from the patient’s birth date. Insurance status was based on the patient’s insurance status at the time of registration at MDACC and categorized as follows: no insurance (include self-payers and patients referred from the county public hospital), Medicare, Medicaid, or any of a variety of private/commercial insurances. Private insurances were combined into one category. Information on each patient’s primary cancer site was categorized as blood, breast, genitourinary, head and neck, or other (primarily brain, central nervous system, and an unknown primary site).
The gender and insurance variables had some missing data. When there were conflicting data for a particular patient’s gender, we coded gender as missing. When the insurance type was missing, data on the patient’s insurance status at the time of registration at MDACC were retrieved from MDACC’s financial department.
Prescription medication fills
Data on the prescription medication name (generic or brand) and institutional billing charges per fill were extracted from pharmacy records. Prescriptions were aggregated by generic and brand names, regardless of strength, dosage form, or method of administration, to identify the 20 most frequently dispensed medications overall and for the treatment of cancer. We then used Rxlist.com (www.rxlist.com), an online medication reference program, to identify each medication’s clinical indication(s). For example, the brand name medication Zofran would be aggregated with its generic, ondansetron, and would be considered as one medication indicated for nausea and vomiting.
We extracted patient billing charge per medication fill in dollars by the date of pickup in the outpatient pharmacy. Patient billing charge included patient copayments and did not include any payments from the patient’s payer or health plan. If the billing charge was missing for a medication fill, we applied a comparable charge from a prescription medication of the same name, dosage, quantity, date of pickup, and patient insurance status. When quantity, date, or patient insurance status differed, the lowest available charge was used. All charges were adjusted to the year 2008 using the US Bureau of Labor’s Annual Producer Price Index for pharmaceutical preparation and manufacturing.7
Data analysis
For patient-level analyses, a PAP user was a patient who received at least one medication through a PAP during the study period. We used descriptive statistics to compare patient characteristics of PAP users versus PAP nonusers. Next, we conducted separate unadjusted binary logit regression analyses (interpreted with odds ratios [ORs] and 95% confidence intervals [CIs]) to estimate the differences in the probability of being a PAP user for each of the patient characteristics. All patient characteristics that were statistically significant at P < 0.20 for the unadjusted analyses8 were included in the final multivariable model. The a priori level of significance was set at P < 0.05 for the multivariable model.
For other analyses conducted at the prescription level, a PAP medication was a medication verified as being provided through a PAP. We used descriptive statistics to compare the 20 most frequently dispensed prescription medications (overall and for anticancer agents specifically) by PAP status and clinical indication. Analyses were conducted in Microsoft Excel and STATA Version 11.9
Results
Study patients and prescription medications
During the 18-month observation period, a monthly mean of 1,550 patients received a monthly total of 19,000 noninvestigational medications in the outpatient pharmacy. Of these patients, 7.5% (n = 1,929) met study eligibility criteria for PAPs and received 1 of the 104 medications provided through PAPs. Thus, there were 979 PAP users and 950 PAP nonusers in the final study population. In total, the study population received 23.3% (n = 77,592) of all outpatient medications administered during this period, of which anticancer agents represented 4% (n = 3,105; Table 1).
Comparison of patient characteristics
In comparison to PAP nonusers, PAP users were, on average, younger (48 vs 52 years), indigent (73% vs 19%), white (50% vs 43%), and covered by Medicaid or were uninsured (75% versus 20%). PAP users also had more prescriptions fills (median = 30 vs 20) during the study period at the institution. Univariate analyses showed that all patient characteristics, except gender, significantly predicted PAP use. Given the strong correlation of indigent and insurance status to PAP use, we conducted post hoc analyses to assess the potential for multicollinearity between the two patient characteristics. The variance inflation factor (VIF = 4.57) did not indicate multicollinearity concerns.
In the adjusted model, patients who were indigent (OR = 16.95; 95% CI: 6.845, 41.960), uninsured (OR = 4.60; 95% CI: 2.118, 9.970), and under the age of 65 years (OR = 2.31; 95% CI: 1.517, 3.509) were 2- to 17- fold more likely than others to be PAP users. Black patients were 31% (P = 0.020) less likely to access PAPs than were white patients.
Overall prescription medication fills The top-20 prescription medication fills from the MDACC outpatient pharmacy differed by PAP user group and PAP status. For PAP users, 88% of the most common medications obtained from PAPs were supportive care agents, including treatments of bacterial infections (n =887 fills; 49/month), antiemetics (n = 492 fills; 27/month), and gastroesophageal reflux disease (n = 492 fills; 27/month). Conversely, treatments for neutropenia and anticoagulation represented nearly half ($1.8 million) of the total charges avoided through PAPs to PAP users ($3.9 million). The most common medications not obtained from PAPs were for treatment of pain (PAP users = 292 fills/month, nonusers = 218 fills/month), versus only 13 fills/ month for pain medications from PAPs. Medications indicated to treat pain and nausea/vomiting accounted for the largest proportion of charges for medications not filled by PAPs for both PAP users and nonusers.
Anticancer agent prescription fills
For both PAP users and nonusers, the top-20 anticancer oral agent fills represented 93% (n = 2,892 of 3,105) of all anticancer oral fills (Table 6), with 16% (n = 454) of these oral fills being provided through PAPs. Among PAP users, anticancer agents from PAPs accounted for 40% of their total charges and 35% of the total number of agents. Temozolomide (Temodar; mean charge/fill = $3,346) represented the highest amount of total charges ($220,857) from PAPs, whereas imatinib (Gleevec; mean charge/fill = $5,372) and dasatinib (Sprycel; mean charge/fill = $5,221) accounted for the highest average charges per fill. Anastrozole (Arimidex; n = 178 fills; 10/month), capecitabine (Xeloda; n = 91 fills; 5/month), and temozolomide (n = 66 fills; 4/month) accounted for 70% of agents from PAPs. PAP users who were given bicalutamide received 100% of those agents from PAPs. Five of the seven oral anticancer agents with no fills from PAPs had initial US Food and Drug Administration approval years before 2000.
Discussion
At MDACC, PAPs are designed to help cancer patients overcome financial barriers to accessing oral supportive and anticancer agents. Over an 18-month observation period, less than 5% of the cancer patients at MDACC who received prescription medications from the outpatient pharmacy were enrolled in a PAP— and these PAPs provided 13% of their medication fills, representing an annualized $3.6 million in pharmaceutical expenditures. In interpreting our findings, several factors should be considered.
Oral anticancer agents accounted for 4% of all prescription medication fills during the study period. Comparatively, an analysis of the 2007 National Ambulatory Medical Care Survey showed that less than 1% of cancer patients were prescribed at least one oral anticancer agent.10 This finding indicates that both nationally and at MDACC, chemotherapy continues to be largely provided parenterally, as there is more of a financial benefit from intravenous therapies that are often reimbursed by insurers as well as PAPs.
In the outpatient pharmacy at MDACC, PAPs provided nearly onethird of oral anticancer fills for PAP users—totaling a mean of $500,000 per month in expenditures. However, three agents, anastrozole (for breast cancer), capecitabine (for breast and GI cancers, primarily), and temozolomide (for brain tumors) accounted for 75% of all of the anticancer agents provided by PAPs. We also found that pharmaceutical companies provided expensive newer, targeted, anticancer agents (primarily dasatinib and imatinib, the two agents with the greatest pharmaceutical per-person expenditures by the PAP program) through PAPs.
Although PAPs filled a strong and focused need for a small number of oral chemotherapy agents for some individuals with breast, GI, and brain cancers, they did not provide much benefit for a wide range of supportive care agents, particularly those that are schedule C and are used to treatcancer pain. Pain is the most prevalent symptom reported by cancer patients, 11 but there were few schedule C pain medications among the most common medications provided through PAPs. These substances are generally not provided by PAPs because of legal and substance abuse concerns.12 However, these medications were commonly prescribed to PAP users and PAP nonusers alike, outside of the PAP program. It would be important to evaluate the comparative success in treating pain among cancer patients at MDACC who receive a limited array of pain medications from PAPs (usually agents that are not substance-controlled by the Drug Enforcement Administration) versus treatment of pain experienced by patients whose medications are not reimbursed by PAPs.
We found that being younger than 65 years old, being indigent, and having no health insurance were the strongest predictors of using a PAP. This finding was expected, given that US adults younger than age 65 are ineligible for outpatient prescription medication coverage through Medicare Part D. However, contrary to expectations, about 45% of PAP users had either private or governmentsupplied health insurance. Because it is not uncommon for cancer patients to endure economic hardship (including bankruptcy) when trying to finance their care,13 healthcare professionals could recommend PAPs and other relevant assistance programs to all of their cancer patients.
With the expansion of health insurance through the Patient Protection and Affordable Health Care Act of 2010, it is hoped that the need for cancer patients to enroll in PAPs will be diminished; yet, given the reality of the high cost of anticancer agents, reimbursement policies for these agents, and tiered formularies among insurers leading to high outof- pocket costs for patients, the need for PAPs is likely to remain. PAPs can be a viable option for some patients, but healthcare professionals should be aware that there are a number of concerns about these programs, including their complex and burdensome application process and often limited variety of available drugs.14
This study is not without its limitations. First, we may have underestimated our sample of PAP patients due to the fact that MDACC did not electronically or systematically track the use of PAPs within its pharmacy database at the time of the study. The institution is in the process of developing such a system.
Second, the data used in this study cannot be assumed to reflect a “closed pharmacy” setting because some patients, particularly those who have health insurance with prescription medication coverage, may have received some of their medications from outside pharmacies.
Third, because insurance status is not necessarily a static characteristic, insurance status in this study was classified based on that at the time of registration with MDACC’s financial department, and no account was taken of changes that might have occurred.
Last, our results are not necessarily generalizable to all cancer populations, time periods, or settings. Cancer patients treated in academic centers such as MDACC may differ from those who are treated in community settings. In particular, fewer than 10% of patients at MDACC qualified for indigent financial assistance in 2007,15 which is likely to have impacted the number of patients who were potentially eligible for PAPs. It is also likely that had our study been conducted prior to the implementation of Medicare Part D, our sample of PAP patients would have been older. Nevertheless, our results may be generalizable to cancer patients receiving care in other academic cancer centers.
Conclusion This study builds upon a previous description of implementing PAPs in a comprehensive cancer center16 as well as contributes to our limited knowledge of the use of PAPs among cancer patients.6 Future studies should prospectively examine cancer patients’ experiences and satisfaction with PAPs from the process of applying to the point of receiving requested therapies and evaluate the effect of PAPs on cancer outcomes in various care settings. Multidisciplinary teams, including pharmacists and clinicians, should establish and recommend valid and relevant clinical endpoints for researchers to use in effectiveness studies of PAPs and cancer patients, particularly as they relate to oral anticancer agent use. Given that these oral agents represent more than 25% of cancer therapies in development,17 future studies of PAPs are ideal for evaluating concerns of accessibility, affordability, and compliance related to these agents.
MDACC is a unique resource for observers of PAPs, as it is the largest cancer center in the United States. However, few cancer patients at MDACC were eligible for and accessed PAPs in the outpatient pharmacy. Although smaller cancer centers may not be able to devote the same degree of financial and personnel resources to their patients as does MDACC, these centers could seek to build relationships with specific pharmaceutical companies that provide PAPs for the oral anticancer and supportive care therapies most commonly prescribed and administered at their centers. Scarce resources could also be utilized in other ways, such as by developing public-private risk pools for establishment of indigent care funds.
Acknowledgments: The authors thank Chun Feng, Jason Lau, and Oliver Max for their special assistance; Dr. Phoenix Do for her study design recommendations; and Karyn Popham for her editorial support. They especially thank Rebecca Arbuckle, RPh, for her support of this project. At the time of the study, Dr. Felder was supported by a Predoctoral Fellowship from The University of Texas School of Public Health Cancer Education and Career Development Program, funded by National Cancer Institute/NIH Grant R25-CA-57712-17.
References
1. Hede K. Increase in oral cancer drugs raises thorny issues for oncology practices. J Natl Cancer Inst 2009;101:1534–1536.
2. Chisholm MA, DiPiro JT. Pharmaceutical manufacturer assistance programs. Arch Intern Med 2002;162:780–784.
3. Duke KS, Raube K, Lipton HL. Patientassistance programs: assessment of and use by safety-net clinics. Am J Health Syst Pharm 2005;62:726–731.
4. Pisu M, Richman J, Allison JJ, Williams OD, Kiefe CI. Pharmaceuticals companies’ medication assistance programs: potentially useful but too burdensome to use? South Med J 2009;102:139–144.
5. Felder TM, Palmer NR, Lal LS, Mullen PD. What is the evidence for pharmaceutical patient assistance programs? a systematic review. J Health Care Poor Underserved 2011;22:24–49.
6. Meropol NJ, Schrag D, Smith TJ, et al. American Society of Clinical Oncology guidance statement: the cost of cancer care. J Clin Oncol 2009;27:3868–3874.
7. United States Department of Labor, Bureau of Labor Statistics: Producer Price Index Industry Data—Pharmaceutical Preparation & Manufacturing; 2010 [updated April 26, 2010]. http://www.bls.gov/ppi/data.htm. Accessed June 22, 2011.
8. Hosmer DW, Lemeshow S. Applied Logistic
Logistic
Regression. New York: Wiley; 2000. 9. StataCorp LP. STATA statistical software. 2009; Release 11.
10. Arora S. Use of oral chemotherapeutic medications in non-traditional ambulatory settings; 2009. http://digarchive.library.vcu. edu/dspace/bitstream/10156/2711/1/Thesis_ MPH_sameer.pdf. Accessed June 22, 2011.
11. Cherny NI. The management of cancer pain. CA Cancer J Clin 2000;50:70–116.
12. Williams K. Accessing patient assistance programs to meet clients’ medication needs. J Am Acad Nurse Pract 2000;12:233– 235.
13. National Survey of Households Affected by Cancer: Kaiser Family Foundation; 2006 [updated November 2006]. http://kff.org/kaiserpolls/ upload/7591.pdf. Accessed June 22, 2011.
14. Choudhry NK, Lee JL, Agnew-Blais J, Corcoran C, Shrank WH. Drug company- sponsored patient assistance programs: a viable safety net? Health Aff (Millwood) 2009;28:827–834.
15. Ackerman T. M.D. Anderson submits its records on charitable care: cancer center hopes to quell Iowa senator’s investigation. Houston Chronicle. October 9, 2008. http:// www.chron.com/disp/story.mpl/metropolitan/ 6050254.html. Accessed June 22, 2011.
16. Johnson PE. Patient assistance programs and patient advocacy foundations: alternatives for obtaining prescription medications when insurance fails. Am J Health Syst Pharm 2006;63(21 suppl 7):S13–S17.
17. Weingart SA, Brown E, Bach PB, et al. National Comprehensive Cancer Network task force report: oral chemotherapy. JNCCN 2008;6(suppl 3):S1–S25.