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Healthcare Costs and Workloss Burden of Patients with Chemotherapy-Associated Peripheral Neuropathy in Breast, Ovarian, Head and Neck, and Nonsmall Cell Lung Cancer

Healthcare Costs and Workloss Burden of Patients with Chemotherapy-Associated Peripheral... Hindawi Publishing Corporation Chemotherapy Research and Practice Volume 2012, Article ID 913848, 10 pages doi:10.1155/2012/913848 Research Article Healthcare Costs and Workloss Burden of Patients with Chemotherapy-Associated Peripheral Neuropathy in Breast, Ovarian, Head and Neck, and Nonsmall Cell Lung Cancer 1 1 2 Crystal T. Pike, Howard G. Birnbaum, Catherine E. Muehlenbein, 2 3 Gerhardt M. Pohl, and Ronald B. Natale Analysis Group, Inc., Boston, MA 02199, USA Eli Lilly and Company, Indianapolis, IN 46285, USA Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA Correspondence should be addressed to Crystal T. Pike, cpike@analysisgroup.com Received 23 September 2011; Accepted 4 January 2012 Academic Editor: Vito Lorusso Copyright © 2012 Crystal T. Pike et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. Chemotherapy-associated peripheral neuropathy (CAPN) is a painful side-effect of chemotherapy. This study assesses healthcare and workloss costs of CAPN patients with breast, ovarian, head/neck, or non-small cell lung cancer (NSCLC) from a third-party payor/employer perspective. Research Design and Methods. Patients with qualifying tumors, and claims for chemotherapy and services indicative of peripheral neuropathy (PN) within 9-months of chemotherapy (cases) were identified in a administrative claims database. Cases were matched 1 : 1 to controls with no PN-related claims based on demographics, diabetes history and propensity for having a diagnosis of PN during the study period (based on resource use and comorbidities in a 3- month baseline period). Average all-cause healthcare costs, resource use and workloss burden were determined. Results.Average healthcare costs were $17,344 higher for CAPN cases than their non-CAPN controls, with outpatient costs being the highest component (with cases having excess costs of $8,092). On average, each CAPN case had 12 more outpatient visits than controls, and spent more days in the hospital. Workloss burden was higher for cases but not statistically different from controls. Conclusion. This study establishes that breast, ovarian, head/neck, or NSCLC patients with CAPN have significant excess healthcare costs and resource use. 1. Introduction by drug and dose and can range across products from 4– 92% [1, 2, 5, 6]. For example, clinical trials of paclitaxel in Chemotherapy-associated peripheral neuropathy (CAPN) is breast cancer list incidence rates for severe CAPN between aneurologicalsideeffect of chemotherapy characterized by 2–33%, with overall CAPN rates upwards of 60% [3, 7, 8]. loss of sensation in the hands and feet, burning or tingling Currently, there are no standard treatments to prevent or in limbs, and, in some cases, loss of hearing and blurred mitigate CAPN, although several drug classes (e.g., tricyclic vision. The neuropathic symptoms are progressive and tend antidepressants, antiepileptic drugs, and adjuvant analgesics) to increase as chemotherapy treatment proceeds. In addition, have shown some activity in reducing neuropathic pain comorbid conditions may exacerbate the severity of CAPN [9, 10]. [1]. For example, diabetes can lead to peripheral neuropathy, Few data exist regarding the health outcomes of CAPN and diabetic patients with pre-existing nerve damage may be patients, CAPN’s effects on chemotherapy treatment, and as- predisposed to more severe forms of CAPN [2–4]. sociated costs. However, Berger suggests neuropathies in gen- The chemotherapy drugs most commonly associated eral can lead to adverse outcomes and higher costs [11]. In with CAPN are taxanes (paclitaxel and docetaxel), vinca alka- particular, Berger found that patients with neuropathies had loids (vincristine and vinorelbine), and platinums (cisplatin, carboplatin, and oxaliplatin). The incidence of CAPN varies healthcare costs triple those of controls; however, the study 2 Chemotherapy Research and Practice did not examine the costs associated with chemotherapy- 2.2.1. Main CAPN Sample. Patients under age 65 were eli- related neuropathies specifically [11]. gible for inclusion in the main sample if they had at least 1 claim with a diagnosis for 1 or more of the following cancers Calhoun conducted a pilot study on the medical and from 1999–2005: NSCLC, breast, ovarian, or head and neck. workloss costs associated with chemotherapy-induced tox- The cancer types were identified using ICD-9-CM codes icities in women with ovarian cancer [12]. Using survey (see Table 1(b)). To identify NSCLC from the overall lung data on 42 patients suffering from chemotherapy-induced cancer sample, patients receiving chemotherapy regimens neurotoxicities, the study found the medical costs directly characteristic of treatment for small cell lung cancer (SCLC) attributable to CAPN were $688 per episode but that indirect were excluded. SCLC treatment was defined in this study as costs (patient and caregiver workloss and paid caregiver doublet therapy with a platinum agent in combination with costs) were over $4,200 per episode. This pilot study relied irinotecan, topotecan, or etoposide, or CCNU, melphalan, on patient recall of medical services used over 3-month and VP-16 CAV regimen chemotherapy treatments. Of the intervals. In addition, the sample was limited to women with patients with a claim for a qualifying tumor, only those with ovarian cancer and did not consider other cancer types. a procedure code indicating chemotherapy administration To the authors’ knowledge, no study has quantified the within 3 months of a claim for a qualifying tumor were comprehensive health outcomes, medical costs, and workloss selected. The date of first such chemotherapy administration burden of CAPN patients with breast, ovarian, head/neck, was considered the index date. To ensure that the index or nonsmall cell lung cancer (NSCLC). The purpose of the event marked the start of a new line of chemotherapy for current study is to assess health outcomes as well as the the tumor, patients were required to have at least 3 months healthcare (i.e., medical and drug) and workloss cost burden of continuous eligibility prior to the index date with no of CAPN patients (cases) in these 4 tumor types from a third- claims for chemotherapy. Since no specific diagnosis code party payor/employer perspective. The first objective is to exists for CAPN, the authors developed an algorithm to compare the healthcare costs of CAPN cases with those of define peripheral neuropathy (PN) using ICD-9-CM codes matched controls who have the same cancer but no CAPN. for related diagnoses and symptoms (see Table 1(b)). Any The second objective is to compare workloss costs in patients PN defined in the 9 months following the index date was with and without CAPN. The third objective is to compare assumed to be CAPN. Thus, patients were classified as the healthcare costs of CAPN cases and non-CAPN controls CAPN if they had evidence of PN within 9 months of first who have comorbid diabetes. By examining these 4 tumor chemotherapy treatment but had no evidence in the 3- types, this study captures the use of the chemotherapeutic month baseline period. Finally, for this sample, patients with agents most commonly associated with CAPN. evidence of diabetes (i.e., a diagnosis of 250.x) from at least 3 months up to 12 months prior to the index date or during 2. Methods the 12 months following the index date were excluded. 2.1. Data. Data were obtained from a database of privately 2.2.2. Diabetic CAPN Sample. A sample of patients with 1 insured administrative claims records (Ingenix Employer of the 4 tumor types, CAPN, and diabetes were selected for Database) that included approximately 8 million beneficia- the secondary analysis. The patient selection criteria were the ries from 40 large US-based companies (1999–2006). The same as in the Main CAPN sample with the exception of the companies have operations nationwide in a broad array of diabetes criteria. Specifically, diabetic CAPN patients were industries and job classifications. The database contains de- identified as those patients with a diagnosis of ICD-9-CM identified beneficiary information including demographics code 250.x anytime from at least 3 months up to 1 year prior (e.g., age and gender), enrollment, and medical and phar- to the index date or during the 12 months following the index macy claims. Utilization measures include date of service, date. diagnoses, procedures, and actual payments to providers. Pharmaceutical drug claims include National Drug Code 2.2.3. CAPN Employee Sample. A subsample of patients from (NDC), fill date, days of supply, quantity, and actual the Main CAPN and Diabetic CAPN samples who were payments. In addition, disability claims and employee wage employees with disability data were selected for the workloss information were available for employees in 23 companies. cost analysis. Note that this sample will not contain all employed persons from the main and diabetic CAPN 2.2. Sample Selection. Three analytic samples consisting of samples but rather will only include the employees of the CAPN cases and matched non-CAPN controls were used subset of companies with disability data available. for this study. The main sample, consisting of cases and controls without diabetes, was used to evaluate the healthcare 2.2.4. Study Period for All Samples. The study period encom- costs and resource use associated with CAPN patients. A passed the 12 months following the index date. Since the sample of cases and controls with diabetes was used in the perspective adopted was that of the payor and the payor secondary analysis to evaluate the costs and resource use incurs no cost for patients who withdraw from coverage, associated with diabetic CAPN patients. Finally, a subsample no requirements were placed on the length of continuous of employed cases and controls was used to assess the eligibility following the index event. The baseline period for workloss burden associated with CAPN patients. Table 1(a) assessing patient history extended 3 months prior to the presents the sample selection. index date except for ascertaining the presence of diabetes. Chemotherapy Research and Practice 3 Table 1: Inclusion criteria and ICD-9-CM codes used for analytic samples. (a) Inclusion criteria Number of patients Criteria 1 4,729,443 Number of beneficiaries under 65 at eligibility start >1 breast, ovarian, head and neck, or nonsmall cell 2 56,261 lung cancer claim from 1999–2005 >1 chemotherapy treatment within 3 months following 3 14,142 a breast, ovarian, head and neck, or nonsmall cell lung cancer diagnosis >3 months of continuous eligibility prior to the first chemotherapy treatment for the qualifying tumor 4 11,009 during which no other chemotherapy treatment was received >1 diagnosis for peripheral neuropathy following first 5 1,245 chemotherapy treatment Peripheral neuropathy within 9 months of first 6 525 chemotherapy treatment Main CAPN sample: no diabetes history Diabetic CAPN sample Employee CAPN subsample (b) ICD-9-CM Diagnosis Codes Used for Identification of CAPN and Cancer CAPN ICD-9-CM code Polyneuropathy due to drugs 357.6 Disturbance of skin sensation 782.0 Inflammatory and toxic neuropathy 357.x Toxic optic neuropathy 377.34 Reflex sympathetic dystrophy 337.2 Cervical root lesions 353.2 Lumbosacral root lesions 353.4 Other mononeuritis of unspecified site 355.7 Mononeuritis of unspecified site 355.9 Neuralgia, neuritis, or radiculitis 729.2 Brachial plexus lesions 353.0 Cancer ICD-9-CM code Nonsmall cell lung cancer 162.x Breast cancer 174.x, 175.x Ovarian 183.x Head and neck 195.0, 140.x, 141.x, 142.x, 143.x, 144.x, 145.x, 146.x, 147.x, 148.x,149.x In all cases, the patients were required to have a minimum of type, index date of chemotherapy, length of followup 3 months eligibility prior to the index date to qualify for the (controls were required to have postindex eligibility of study. at least as long as their matched case), and the estimated likelihood of developing CAPN. Each case was matched 2.3. Matching. Cases in the main CAPN sample and the 1 : 1 to a control using an optimal matching algorithm [13]. diabetes CAPN sample were separately matched to controls Likelihood of developing CAPN was derived as a propensity selected from among the set of NSCLC, breast, ovarian, score from a logistic regression model based on resource use and comorbidities during the baseline period. Specif- and head/neck cancer patients receiving chemotherapy who did not have a diagnosis for CAPN-related symptoms ically, the model included age, sex, Charlson Comor- at any time in the claims history and were under age bidity Index (CCI) [14], number of inpatient, primary 65. Controls were matched to cases based on age, gender, care, oncology, neurology, and other physician visits, and employment status (employee versus nonemployee), cancer binary variables indicating whether patient went to the 4 Chemotherapy Research and Practice emergency room or had depression or uncomplicated hyper- 2.5. Statistical Analyses. Baseline characteristics (demo- tension. graphics, comorbidities, resource use rates) were summa- rized as proportions of the sample with the characteristic. The time period over which controls contributed to Continuous measures (e.g., healthcare costs, workloss costs, the outcomes measures was truncated at the end of the resource use amount) were summarized by mean and stan- observation period for their matching case (i.e., the earlier of dard deviation. Comparisons of matched pairs of categorical either 12 months or when cases dropped from the database). variables used McNemar tests. Comparisons of the differ- ences in continuous measures between cases and controls 2.4. Measures. Healthcare costs were stratified into 3 mutu- used paired t-tests. Excess costs of CAPN cases compared ally exclusive groups: chemotherapy costs, drug costs, and with controls (i.e., costs of CAPN cases minus those of medical costs. Costs were computed as the paid (reimbursed) controls) were compared between diabetic and nondiabetic amount by the insurer to the health-care provider and patients using a 2-sample t-test. All analyses were conducted were annualized to 2006 U.S. Dollars using the Consumer using SAS version 9.1 (SAS Institute Inc., Cary, NC). P- Price Index for medical care. Chemotherapy costs included values less than or equal to 0.05 were considered statistically medical claims with a chemotherapy procedure code and significant. pharmacy claims for oral chemotherapy agents, identified by NDCs. Drug costs included all pharmaceutical claims 3. Results other than chemotherapy claims. Medical costs included claims for inpatient, emergency department (ED), and The main study sample for the healthcare cost and resource outpatient/other care. Costs included all claims associated use analysis contained 454 cases and controls without dia- with any service provided to the case/control during the betes (see Table 1(a)). The diabetes sample for the secondary study period regardless of diagnosis, procedure, or drug. analysis contained 71 diabetic cases and controls. The The subset of pharmaceutical and medical costs that could employee subsample for the workloss cost and resource use be directly attributed to CAPN was estimated as follows: analysis contained 78 cases and controls. CAPN-related drug costs included those for drugs potentially used for CAPN (i.e., amitriptyline, gabapentin, amifostine, 3.1. Baseline Characteristics. Tables 2(A) and 3(A) show the glutamine, tricyclic antidepressants, anti-epileptics, NSAIDs, baseline comparison of CAPN cases and their matched non- and opioids) and CAPN-related medical costs included those CAPN controls within the main sample. Cases and controls from claims with a primary or secondary diagnosis of a were balanced in terms of types of cancer and CCI. However, CAPN-related symptom (see Table 1(b)). CAPN cases had more congestive heart failure (4% versus Healthcare resource use consisted of hospitalizations, 2%, P = 0.0412) and uncomplicated hypertension (17% emergency department (ED), and outpatient/other services versus 11%, P = 0.0164), whereas the control group had a (reported by type of visit). The resource use components higher rate of complicated hypertension (3% versus 1%, P = were defined using provider specialty codes and/or place 0.0290). Resource use was generally the same between cases of service codes on the claims. All claims during the study and controls; however, there were more cases with neurology period were included in assessing resource use, regardless specialist visits than controls (5% versus 2%, P = 0.0482). of the underlying reason for a visit. In addition, the pro- The number of neurology visits and neurology costs were not portion of patients using CAPN-related drugs, and specific significantly different. chemotherapy agents were measured. Workloss days and costs consisted of disability and med- 3.2. Study Period Descriptive Characteristics, Healthcare Re- ically related absenteeism. Workloss costs during the 12- source Use, and Costs. CAPN cases had significantly higher month study period included actual employer payments rates and counts of comorbidities and resource use dur- for disability days plus imputed costs for medically related ing the study period compared with matched non-CAPN absenteeism. Medically related absenteeism costs were controls (Tables 4(A) and 5(A)). Significantly more cases imputed by multiplying the number of days with medical had fibromyalgia, obesity, and uncomplicated hypertension services resource use by the employee’s wage: each hospi- during the study period than their matched controls. Cases talization day accounted for a full day of workloss, and also had a higher CCI during the study period (4.7 versus outpatient visits accounted for half a day of workloss. As with 4.1, P< 0.0001). There were no differences in the classes healthcare costs, total workloss costs were not limited to only of chemotherapy agents used by cases and controls. The those related to a particular condition. most common chemotherapeutic agents used by cases and Patient characteristics included demographics, employ- controls were taxanes (33%, 28%) and platinums (20%, ment status (employee versus nonemployee), cancer type, 18%). Significantly more cases used a CAPN-related drug cancer stage (metastatic versus not metastatic), and comor- than controls (72% versus 56%, P< 0.0001). Cases had bidities identified using claims during baseline period and substantially higher rates and amounts of use of both in- the 12-month study period. Metastatic cancer was defined patient and outpatient visits during the study period. More using claims with diagnoses for metastases (ICD-9-CM codes cases were hospitalized at least once compared with controls 196.0-199.1). The CCI was calculated from the claims data (51% versus 37%, P< 0.0001). CAPN cases had significantly and individual physical comorbidities included in the index higher rates and amounts of use for all outpatient compo- which were also identified [14]. nents except for primary care visits and lab/pathology. More Chemotherapy Research and Practice 5 Table 2: Three-month baseline demographics and comorbidities of CAPN cases and non-CAPN controls. (A) Main Sample: no diabetes (B) Diabetes Sample Cases Controls P-value Cases Controls P-value No. % No. % No. % No. % N 454 454 71 71 Demographics Age (mean, SD) 53.9 7.5 53.7 9.3 0.0006 58.5 5.0 57.9 8.3 0.5044 Gender (n, % male) 69 15% 69 15% 1.0000 13 18% 13 18% 1.0000 Employment Status (n, % employed) 75 17% 75 17% 1.0000 3 4% 3 4% 1.0000 Months followup (mean) 11.1 2.2 11.3 1.7 12-month followup 366 81% 56 79% Time to CAPN (mean days, SD) 147.5 82.9 137.2 85.7 1–3 months 125 27% 22 31% 3–6 months 149 33% 26 37% 6–9 months 179 39% 23 33% Cancer type Nonsmall cell lung 82 18% 82 18% 1.000 18 25% 18 25% 1.000 Breast 316 70% 316 70% 1.000 42 59% 42 59% 1.000 Ovarian 28 6% 28 6% 1.000 7 10% 7 10% 1.000 Head and neck 27 6% 27 6% 1.000 4 6% 4 6% 1.000 Metastatic cancer 168 37% 164 36% 0.7883 33 46% 20 28% 0.0374 Comorbidities Depressive disorders 23 5% 31 7% 0.2673 2 3% 3 4% 0.6547 Congestive heart failure 20 4% 10 2% 0.0412 7 10% 8 11% 0.7963 Fibromyalgia 7 2% 7 2% 1.0000 4 6% 1 1% 0.1797 Obesity 8 2% 2 0% 0.0578 2 3% 0 0% 0.0578 Hypertension—uncomplicated 76 17% 52 11% 0.0164 22 31% 24 34% 0.7316 Hypertension—complicated 4 1% 13 3% 0.0290 4 6% 0 0% 0.0290 Other cancers 83 18% 74 16% 0.4352 17 24% 21 30% 0.4497 Charlson Comorbidity Index 4.4 4.3 0.4913 6.0 4.5 0.0043 CAPN indicates chemotherapy-associated peripheral neuropathy; SD, standard deviation. P-values are determined using McNemar tests for proportions and paired t-tests for continuous measures. cases saw a neurologist than did controls (29% versus 6%, 0.5744). CAPN-related drug and medical costs accounted for P< 0.0001). approximately 2% of total healthcare costs. Table 6(A) shows the healthcare cost comparison for cases and controls. For cases, mean annual per capita health- 3.3. Workloss and Costs. There were no statistically signif- care costs were $69,950 versus $52,606 per control, with an icant differences in workloss measures between the subset excess annual per patient cost of $17,344 (P< 0.0001). Mean of 78 employees with CAPN and their matched non-CAPN excess annual per patient healthcare costs for cases versus controls (Table 7). More cases had disability claims than controls were $36,660 for head and neck cancer, $18,790 controls (35% versus 26%, resp.). Cases also had almost twice for nonsmall cell lung cancer, $16,940 for breast cancer, as many disability days as their matched controls (37.4 versus and $5,140 for ovarian and all were statistically significant 20.4 days, resp.). While almost all cases and controls had at (data not shown). Cases had significantly higher component least 1 medically related absenteeism day (95% and 97%, costs compared with controls. Outpatient costs were the resp.), cases missed 6 additional days over the 12-month highest component for both cases and controls. However, study period compared with controls. the excess costs of outpatient and inpatient components were Averageannualworklosscosts were approximately25% similar with cases having excess annual outpatient costs of higher for cases than controls ($11,298 versus $9,043, resp.) $8,092 per patient (P< 0.0001) and excess annual inpatient with a $2,255 annual per patient difference (Table 7). Cases costs of $7,552 per patient (P< 0.0001). Annual oncology- had both higher disability and higher medically-related related costs (i.e., chemotherapy and oncologist specialist absenteeism costs than controls ($4,970 versus $3,356 for costs) were $22,453 for cases compared with $19,362 for disability and $6,329 versus $5,687 for medically-related controls, with the majority of costs being chemotherapy costs absenteeism). However, workloss cost differences were not ($16,984 and $16,169 for cases and controls, resp., P = statistically significant. 6 Chemotherapy Research and Practice Table 3: Three-month per-capita baseline resource use and healthcare costs of CAPN cases and non-CAPN controls. (A) Main Sample: no diabetes (B) Diabetes Sample a a Cases Controls P-value Cases Controls P-value No. % No. % No. % No. % N 454 454 71 71 Resource use rate Hospitalizations 204 45% 193 43% 0.4692 43 61% 33 46% 0.1138 ED visits 75 17% 68 15% 0.5139 21 30% 16 23% 0.3980 Outpatient visits 444 98% 445 98% 0.8185 71 100% 70 99% 0.8185 Oncology 188 41% 174 38% 0.3408 26 37% 30 42% 0.4795 Neurology 22 5% 11 2% 0.0482 5 7% 1 1% 0.1025 a a Resource use amount Mean (SD) Mean (SD) P-value Mean (SD) Mean (SD) P-value Hospitalizations 1.96 (5.53) 1.48 (3.21) 0.0956 3.48 (5.02) 4.10 (9.75) 0.5702 ED visits 0.24 (0.70) 0.21 (0.58) 0.3550 0.41 (0.73) 0.35 (0.76) 0.6310 Outpatient visits 11.37 (6.80) 11.25 (7.40) 0.7449 12.80 (6.08) 11.28 (6.76) 0.1420 Oncology 1.40 (3.06) 1.33 (3.47) 0.6673 1.38 (3.10) 1.44 (2.97) 0.9040 Neurology 0.06 (0.31) 0.03 (0.22) 0.0848 0.07 (0.26) 0.01 (0.12) 0.1029 Total costs $17,797 ($22,255) $17,180 ($25,240) 0.6698 $22,308 ($24,970) $21,061 ($22,748) 0.6898 Drug costs $433 ($857) $467 ($1,148) 0.6064 $800 ($868) $646 ($824) 0.2761 Medical costs $17,363 ($22,185) $16,712 ($25,140) 0.6527 $21,508 ($24,871) $20,415 ($22,636) 0.7268 Inpatient $6,496 ($19,301) $5,928 ($21,811) 0.6632 $11,220 ($22,256) $9,382 ($21,412) 0.4845 ED $127 ($826) $102 ($576) 0.6043 $125 ($290) $122 ($340) 0.9490 Outpatient $10,336 ($10,186) $10,328 ($10,282) 0.9900 $9,725 ($8,672) $10,358 ($9,840) 0.6935 Oncology $438 ($1,329) $439 ($1,796) 0.9841 $379 ($996) $431 ($1,452) 0.7989 Neurology $10 ($61) $9 ($108) 0.8812 $24 ($163) $1 ($7) 0.2435 CAPN indicates chemotherapy-associated peripheral neuropathy; SD, standard deviation; ED, emergency department. P-values are determined using McNemar tests for proportions and paired t-tests for continuous measures. Table 4: Chemotherapy agents and comorbidities of CAPN cases and non-CAPN controls during the 12-month study period. (A) Main Sample: no diabetes (B) Diabetes Sample a a Cases Controls P-value Cases Controls P-value No.%No.% No.%No.% N 454 454 71 71 Metastatic cancer 171 38% 136 30% 0.0097 30 42% 22 31% 0.1306 Classes of select chemotherapy agents used Taxanes 148 33% 125 28% 0.0978 30 42% 17 24% 0.0236 Vinca Alkaloids 18 4% 14 3% 0.4497 3 4% 2 3% 0.6547 Platinums 90 20% 80 18% 0.4014 17 24% 20 28% 0.5775 Comorbidities Depressive disorders 68 15% 50 11% 0.0804 8 11% 3 4% 0.1317 Congestive heart failure 23 5% 20 4% 0.6219 12 17% 12 17% 1.0000 Fibromyalgia 37 8% 8 2% <.0001 8 11% 1 1% 0.0196 Obesity 9 2% 2 0% <.0001 1 1% 0 0% 0.2568 Hypertension—uncomplicated 114 25% 83 18% 0.0134 33 46% 35 49% 0.7576 Hypertension—complicated 13 3% 13 3% 1.0000 5 7% 1 1% 0.1025 Other cancers 124 27% 101 22% 0.0838 20 28% 19 27% 0.8415 Charlson Comorbidity Index 4.7 4.1 <.0001 7.0 5.6 0.0052 CAPN indicates chemotherapy-associated peripheral neuropathy. P-values are determined using McNemar tests for proportions and paired t-tests for continuous measures. Other cancers include all cancers other than head and neck, breast, non-small cell lung, and ovarian. Chemotherapy Research and Practice 7 Table 5: Resource use of CAPN cases and non-CAPN controls during the 12-month study period. (A) Main Sample: no diabetes (B) Diabetes Sample a a Cases Controls P-value Cases Controls P-value No.%No.% No.%No.% N 454 454 71 71 Resource use rate Medical Hospitalizations 231 51% 166 37% <.0001 48 68% 32 45% 0.0136 ED visits 213 47% 170 37% 0.0037 42 59% 27 38% 0.0222 Outpatient visits 453 100% 447 98% 0.0339 71 100% 70 99% 0.0339 Oncology 288 63% 250 55% 0.0075 43 61% 39 55% 0.5050 Neurology 133 29% 29 6% <.0001 30 42% 5 7% <.0001 Primary care 354 78% 345 76% 0.4726 59 83% 60 85% 0.8185 Other physician 444 98% 428 94% 0.0035 71 100% 66 93% 0.0035 Lab/pathology 181 40% 160 35% 0.1540 21 30% 22 31% 0.8694 Other outpatient 400 88% 369 81% 0.0030 68 96% 61 86% 0.0522 Prescription drug use At least 1 CAPN-related drug 329 72% 256 56% <.0001 66 93% 46 65% 0.0003 a a Resource use amount Mean (SD) Mean (SD) P-value Mean (SD) Mean (SD) P-value Medical Hospitalizations 5.6 (11.69) 3.2 (7.77) 0.0001 9.1 (14.38) 6.2 (13.44) 0.2195 ED visits 1.1 (2.80) 0.6 (1.28) 0.0022 1.6 (1.98) 0.8 (1.35) 0.0064 Outpatient visits 51.3 (29.57) 39.8 (26.81) <.0001 56.9 (27.02) 38.5 (25.10) <.0001 Oncology 12.7 (18.92) 9.2 (15.55) 0.0021 12.6 (16.97) 7.5 (10.62) 0.0322 Neurology 0.6 (1.29) 0.1 (0.51) <.0001 1.1 (1.87) 0.1 (0.56) 0.0002 Primary care 6.9 (12.65) 5.0 (8.74) 0.0085 7.4 (10.25) 5.7 (5.64) 0.2454 Other physician 22.1 (21.22) 17.2 (18.82) 0.0001 25.9 (20.63) 18.6 (18.82) 0.0217 Lab/pathology 1.1 (2.62) 0.9 (2.49) 0.2127 0.8 (3.59) 1.1 (3.93) 0.6594 Other outpatient 13.6 (16.47) 11.4 (15.97) 0.0349 15.5 (15.37) 11.0 (16.56) 0.0905 CAPN indicates chemotherapy-associated peripheral neuropathy; SD, standard deviation; ED, emergency department. P-values are determined using McNemar tests for proportions and paired t-tests for continuous measures. 3.4. Secondary Analysis of CAPN and Diabetes. Tables 2(B) (P< 0.0001). CAPN-related drugs were used by 93% of cases and 3(B) show the baseline comparison of diabetic cases and compared with 65% of controls (P = 0.0003). their matched diabetic controls. Cases had more metastatic For cases, annual per capita healthcare costs were disease (46% versus 28%, P = 0.0374), complicated hyper- $76,555 versus $54,816 per control, with an excess annual tension (6% versus 0%, P = 0.0290), and a higher CCI per patient cost of $21,739 (P = 0.0273, Table 6(B)). Annual than controls (6.0 versus 4.5, P = 0.0043). Resource use oncology-related costs were $25,181 for cases compared with was generally well balanced; however, cases did have more $15,377 for controls, with the majority of these costs being primary care visits than controls (2.75 versus 1.75, P = chemotherapy costs ($20,990 and $13,033 for cases and con- 0.0136). There were no statistically significant differences in trols, resp., P = 0.0670). The diabetic case’s annual per capita baseline costs. excess costs were higher than the control’s costs ($21,739 Cases had significantly higher rates and counts of re- versus $17,344), however, this difference was not statistically source use during the study period compared with controls significant. (see Tables 4(B) and 5(B)). More cases than controls used taxanes (42% versus 24%, P = 0.0236). More cases were 4. Discussion hospitalized compared with controls (68% versus 45%, P = 0.0136) though the days per capita were not statistically This study is the first to use claims data to estimate the excess different (9.1 versus 6.2 for cases and controls, resp., P = costs of CAPN patients in breast, nonsmall cell lung, ovarian, 0.2195). Six times as many cases had a neurology specialist and head and neck cancer over a matched sample of cancer visit during the study period compared with controls (42% patients without CAPN. This study also included a secondary versus 7%, P< 0.0001). Cases also had 18.4 more outpatient analysis to examine the excess costs of CAPN patients among visits during the study period on average than the controls patients with comorbid diabetes. 8 Chemotherapy Research and Practice Table 6: Per capita healthcare costs for CAPN cases and non-CAPN controls during the 12-month study period. (A) Main Sample: no diabetes (B) Diabetes Sample a a Cases Controls P-value Cases Controls P-value mean (SD) mean (SD) mean (SD) mean (SD) N 454 454 71 71 Total healthcare costs $69,950 ($66,913) $52,606 ($55,554) <.0001 $76,555 ($63,379) $54,816 ($68,115) 0.0273 Chemotherapy costs $16,984 ($21,248) $16,169 ($27,055) 0.5744 $20,990 ($31,501) $13,033 ($19,725) 0.0670 Drug costs $3,744 ($5,333) $3,071 ($4,927) 0.0419 $6,017 ($7,461) $4,223 ($6,100) 0.1163 CAPN-related drugs $595 ($1,590) $328 ($1,041) 0.0016 $718 ($1,401) $371 ($782) 0.0832 Medical costs $49,223 ($56,500) $33,366 ($36,931) <.0001 $49,548 ($46,428) $37,561 ($57,723) 0.1614 Inpatient $14,050 ($35,793) $6,498 ($15,558) <.0001 $19,181 ($38,190) $15,148 ($44,098) 0.5637 ED $474 ($1,093) $263 ($730) 0.0005 $798 ($1,817) $243 ($535) 0.0172 Outpatient $34,698 ($36,712) $26,606 ($29,913) <.0001 $29,569 ($21,339) $22,170 ($29,244) 0.0921 Oncology $5,469 ($15,923) $3,193 ($8,478) 0.0072 $4,191 ($6,950) $2,344 ($4,729) 0.0554 Neurology $129 ($319) $46 ($433) 0.0011 $326 ($843) $44 ($278) 0.0103 Primary care $7,772 ($12,454) $6,543 ($9,920) 0.0979 $6,024 ($7,341) $4,472 ($5,965) 0.1252 Other physician $7,437 ($13,782) $6,804 ($17,452) 0.5247 $6,235 ($11,447) $5,150 ($16,025) 0.6502 Lab/pathology $414 ($1,825) $289 ($1,490) 0.2632 $485 ($2,027) $110 ($193) 0.1237 Other outpatient $13,476 ($24,509) $9,731 ($18,345) 0.0064 $12,307 ($16,297) $10,049 ($20,812) 0.4798 CAPN-related medical costs $725 ($2,005) $491 ($762) CAPN indicates chemotherapy-associated peripheral neuropathy; SD, standard deviation; ED, emergency department. P-values are determined using McNemar tests for proportions and paired t-tests for continuous measures. Table 7: Per capita workloss days and costs during the 12-month The results suggest that CAPN patients are associated study period. with a significant and substantial economic burden among the privately insured U.S. population. Cases with CAPN had Employee subsample on average $17,344 higher healthcare costs during the 12- Cases Controls P-value month study period compared with controls without CAPN. Compared with controls, more cases were hospitalized, had No. % No. % an emergency department visit, saw an oncologist or neu- 78 78 rologist, and had other outpatient visits. In addition, each Workloss rate case with CAPN averaged 12 more outpatient visits and spent more days in the hospital. This suggests that in addition to Medically 74 95% 76 97% 0.4142 related the excess cost burden to third-party payors, the patients absenteeism themselves may (depending on their insurance benefits) experience a large burden in terms of out-of-pocket costs 27 35% 20 26% 0.2367 Disability (e.g., copayments, coinsurance) and time spent on medical mean (SD) Mean (SD) P-value Workloss days care. Medically CAPN can lead to increased costs as a result of services 31.5 (28.1) 25.3 (18.2) 0.0573 related specifically aimed at mitigating the PN (e.g., increased physi- absenteeism cian visits to monitor the PN, costs of PN treatment) and sec- 37.4 (75.4) 20.4 (50.8) 0.1048 Disability ondary effects, such as switches in chemotherapy regimens mean (SD) mean (SD) P-value or exacerbated cancer. This study separately estimated the Workloss costs costs for CAPN-related services and found they accounted Total employer $11,298 ($11,830) $9,043 ($12,416) 0.2161 for less than 2% of healthcare costs during the 12-month costs study period. While a significantly higher proportion of Medically CAPN patients did use the pharmacologic treatments used $6,329 ($7,136) $5,687 ($6,200) 0.5012 related to manage neuropathic symptoms, these drugs are often absenteeism generic or lower cost relative to cancer treatments and $4,970 ($10,994) $3,356 ($10,284) 0.3134 Disability overall healthcare costs. CAPN-related medical costs were SD indicates standard deviation. low suggesting that the excess utilization demonstrated by P-values are determined using McNemar tests for proportions and paired cases was not directly attributed to CAPN. However, the t-tests for continuous measures. CAPN-related costs as measured here may understate the Workloss rate defined as the number of people with ≥1 disability claim or ≥1 instance of medically-related absenteeism. true burden related specifically to CAPN. First, because there Chemotherapy Research and Practice 9 are no specific diagnoses for CAPN, PN-related diagnoses confounding factors not available in this database. Moreover, may be underreported on claims. In addition, the secondary because CAPN does not have a specific diagnosis code and is effects of CAPN mentioned above are not included in the not consistently recorded in claims data, there are challenges CAPN-related subset of costs presented here but rather are in identifying the condition. Physicians may not report included in the chemotherapy, drug, and medical costs. CAPN unless the impairment is severe enough to affect a Overall, this study finds that patients with CAPN expe- patient’s activities of daily living or warrant alterations to rience significantly increased costs and resource use. It is cancer treatment [1]. Thus, this study may include more important not to conclude that all of the excess costs are severe cases of CAPN and may have under identified CAPN caused by CAPN. Since the cases and controls were matched patients. The algorithm used for identifying CAPN in this during the baseline period, the results suggest that CAPN study has not been validated. It is possible that the PN is a serious condition that should be carefully monitored identified was due to other causes. Another study limitation in clinical practice. Improvements to the diagnostic tools is that due to data availability, cases and controls are matched for CAPN severity and investigation of therapies that treat using only 3 months of baseline data and information on CAPN without negatively impacting the cancer treatment cancer stage beyond metastatic/nonmetastatic is not avail- could benefit both patients and payors. able. A longer baseline period using a larger database with Calhoun’s pilot study of chemotherapy-induced toxicity clinical information on cancer stage may allow for additional found that the direct CAPN costs for women with ovarian controls. The lack of restrictions on the length of continuous cancer are $688 for episodes up to 9 months, compared with eligibility following index date is another possible limitation. our findings that CAPN-related costs are on average $1,320 This limitation could potentially lead to censoring of costs if over a period up to 12 months [12]. Calhoun’s study relied a patient’s plan were to have withdrawn from the database on patient reported utilization and standard fee data whereas while the patient was continuing to incur costs; however, no data here are actual reimbursements, which may, in addition such instances occurred in the study and the average length to the difference in length of followup, explain the differences of followup for patients in the study is 11.1 months. Finally, in estimates. Calhoun also analyzed indirect costs based small sample sizes, particularly in the head and neck, ovarian, on national labor force, employment, and earnings data, workloss cost, and diabetic analyses, limited both the types including patient workloss, caregiver workloss, and paid of comparisons as well as the robustness of the statistical caregiver costs. Calhoun found indirect costs were $4,220, inferences. Though this study reports directional differences with 67% of that due to caregiver workloss. Patient workloss in workloss outcome measures, no significant differences costs were $620 per patient per episode compared with our were found, potentially due to the small sample size. findings of $642 per patient per year in excess medically related absenteeism costs. Though Calhoun did not include 5. Conclusion disability costs, this study found CAPN patients had mean excess per patient per year disability costs of $1,614. While CAPN patients are associated with significantly higher the workloss findings were not statistically significant, this healthcare costs and resource use in patients with breast, may be due to the small sample size. It is important to ovarian, head/neck, or NSCLC. The excess healthcare cost note that the workloss cost estimates reported in this study of CAPN is underestimated when only the cost for med- may differ from actual employer costs depending on the ical or pharmacy claims directly for CAPN is considered. employer’s paid time off policies. Improvements in clinical assessments and treatments for Healthcare costs and resource use were calculated for CAPN would be useful for patients and payors. diabetic CAPN patients as a secondary analysis as literature suggests that diabetes may exacerbate the risk and severity of CAPN. With the prevalence of diabetes increasing, it is Acknowledgments important to assess how diabetic CAPN patients may differ from controls and nondiabetic CAPN patients. The results R. B. Natale of Cedars-Sinai Medical Center, Los Angeles, demonstrated that diabetes may, indeed, be associated with CA, USA served as a clinical consultant to the study. The increased cost in patients with CAPN, as excess costs of authors would like to thank Rebecca Kaufman for her diabetic CAPN patients were 25% higher than for nondi- assistance with this study. Previous presentations of this abetic CAPN patients. However, the comparison between study are as follows: C. T. Pike, H. G. Birnbaum, R. J. diabetic and nondiabetic CAPN patients was not statistically Kaufman, C. E. Muehlenbein, G. M. Pohl, R. B. Natale, significant, perhaps due to the small sample of diabetic direct healthcare and workloss burden of chemotherapy- CAPN patients. In addition, although diabetic cases were associated peripheral neuropathy in breast, ovarian, head balanced with their controls in terms of costs and resource and neck, and nonsmall cell lung cancer; value Health 2009; use, a higher proportion of cases had metastatic cancer and 12(3):A1-A19. Oral Presentation ND2 at ISPOR 14th Annual the CCI of cases was significantly higher than controls. Both International Meeting, 16–20 May 2009, Orlando, Florida, these factors could impact the excess cost findings. United States. This study was sponsored by Eli Lilly and This study is limited by the lack of clinical measures, Company, Indianapolis, IN, USA. C. Muehlenbein and G. which is common to research that uses claims data. While M. Pohl are employees of Eli Lilly and Company. C. T. Pike propensity score matching was used to adjust for many and H. G. Birnbaum are employees of Analysis Group, Inc., baseline group differences, the possibility exists of other Boston, MA, which received funding for this study. 10 Chemotherapy Research and Practice References [1] F. H. Hausheer, R. L. Schilsky, S. Bain, E. J. Berghorn, and F. Lieberman, “Diagnosis, management, and evaluation of chemotherapy-induced peripheral neuropathy,” Seminars in Oncology, vol. 33, no. 1, pp. 15–49, 2006. [2] S. Quasthoff and H. P. Hartung, “Chemotherapy-induced peripheral neuropathy,” Journal of Neurology, vol. 249, no. 1, pp. 9–17, 2002. [3] J. J. Lee and S. M. Swain, “Peripheral neuropathy induced by microtubule-stabilizing agents,” Journal of Clinical Oncology, vol. 24, no. 10, pp. 1633–1642, 2006. [4] H. Gogas, F. Shapiro, C. Aghajanian et al., “The impact of diabetes mellitus on the toxicity of therapy for advanced ovarian cancer,” Gynecologic Oncology, vol. 61, no. 1, pp. 22– 26, 1996. [5] C. C. P. Verstappen, J. J. Heimans, K. Hoekman, and T. J. Postma, “Neurotoxic complications of chemotherapy in patients with cancer: clinical signs and optimal management,” Drugs, vol. 63, no. 15, pp. 1549–1563, 2003. [6] B. Dunlap and J. A. Paice, “Chemotherapy-induces peripheral neuropathy: a need for standardization in measurement,” Journal of Supportive Oncology, vol. 4, no. 8, pp. 398–399, 2006. [7] M.A.Wampler andE.H.Rosenbaum,“Chemotherapy- induced peripheral neuropathy fact sheet. Cancer Support- ive Care Programs,” 2008, http://www.cancersupportivecare .com/nervepain.php. [8] S. Mielke, A. Sparreboom, and K. Mross, “Peripheral neu- ropathy: a persisting challenge in paclitaxel-based regimes,” European Journal of Cancer, vol. 42, no. 1, pp. 24–30, 2006. [9] T.J.Kaley andL.M.Deangelis, “Therapy of chemotherapy- induced peripheral neuropathy,” British Journal of Haematol- ogy, vol. 145, no. 1, pp. 3–14, 2009. [10] M. M. Backonja, “Use of anticonvulsants for treatment of neuropathic pain,” Neurology, vol. 59, no. 5, pp. S14–S17, [11] A. Berger, E. M. Dukes, and G. Oster, “Clinical characteristics and economic costs of patients with painful neuropathic disorders,” Journal of Pain, vol. 5, no. 3, pp. 143–149, 2004. [12] E. A. Calhoun, C. H. Chang, E. E. Welshman, D. A. Fishman, J. R. Lurain, and C. L. Bennett, “Evaluating the total costs of chemotherapy-induced toxicity: results from a pilot study with ovarian cancer patients,” Oncologist, vol. 6, no. 5, pp. 441– 445, 2001. [13] P. R. Rosenbaum, “Optimal matching for observational stud- ies,” Journal of the American Statistical Association, vol. 84, pp. 1024–1032, 1989. [14] M. E. Charlson, P. Pompei, K. A. Ales, and C. R. MacKenzie, “A new method of classifying prognostic comorbidity in longitudinal studies: development and validation,” Journal of Chronic Diseases, vol. 40, no. 5, pp. 373–383, 1987. 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Healthcare Costs and Workloss Burden of Patients with Chemotherapy-Associated Peripheral Neuropathy in Breast, Ovarian, Head and Neck, and Nonsmall Cell Lung Cancer

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2090-2107
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10.1155/2012/913848
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Abstract

Hindawi Publishing Corporation Chemotherapy Research and Practice Volume 2012, Article ID 913848, 10 pages doi:10.1155/2012/913848 Research Article Healthcare Costs and Workloss Burden of Patients with Chemotherapy-Associated Peripheral Neuropathy in Breast, Ovarian, Head and Neck, and Nonsmall Cell Lung Cancer 1 1 2 Crystal T. Pike, Howard G. Birnbaum, Catherine E. Muehlenbein, 2 3 Gerhardt M. Pohl, and Ronald B. Natale Analysis Group, Inc., Boston, MA 02199, USA Eli Lilly and Company, Indianapolis, IN 46285, USA Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA Correspondence should be addressed to Crystal T. Pike, cpike@analysisgroup.com Received 23 September 2011; Accepted 4 January 2012 Academic Editor: Vito Lorusso Copyright © 2012 Crystal T. Pike et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. Chemotherapy-associated peripheral neuropathy (CAPN) is a painful side-effect of chemotherapy. This study assesses healthcare and workloss costs of CAPN patients with breast, ovarian, head/neck, or non-small cell lung cancer (NSCLC) from a third-party payor/employer perspective. Research Design and Methods. Patients with qualifying tumors, and claims for chemotherapy and services indicative of peripheral neuropathy (PN) within 9-months of chemotherapy (cases) were identified in a administrative claims database. Cases were matched 1 : 1 to controls with no PN-related claims based on demographics, diabetes history and propensity for having a diagnosis of PN during the study period (based on resource use and comorbidities in a 3- month baseline period). Average all-cause healthcare costs, resource use and workloss burden were determined. Results.Average healthcare costs were $17,344 higher for CAPN cases than their non-CAPN controls, with outpatient costs being the highest component (with cases having excess costs of $8,092). On average, each CAPN case had 12 more outpatient visits than controls, and spent more days in the hospital. Workloss burden was higher for cases but not statistically different from controls. Conclusion. This study establishes that breast, ovarian, head/neck, or NSCLC patients with CAPN have significant excess healthcare costs and resource use. 1. Introduction by drug and dose and can range across products from 4– 92% [1, 2, 5, 6]. For example, clinical trials of paclitaxel in Chemotherapy-associated peripheral neuropathy (CAPN) is breast cancer list incidence rates for severe CAPN between aneurologicalsideeffect of chemotherapy characterized by 2–33%, with overall CAPN rates upwards of 60% [3, 7, 8]. loss of sensation in the hands and feet, burning or tingling Currently, there are no standard treatments to prevent or in limbs, and, in some cases, loss of hearing and blurred mitigate CAPN, although several drug classes (e.g., tricyclic vision. The neuropathic symptoms are progressive and tend antidepressants, antiepileptic drugs, and adjuvant analgesics) to increase as chemotherapy treatment proceeds. In addition, have shown some activity in reducing neuropathic pain comorbid conditions may exacerbate the severity of CAPN [9, 10]. [1]. For example, diabetes can lead to peripheral neuropathy, Few data exist regarding the health outcomes of CAPN and diabetic patients with pre-existing nerve damage may be patients, CAPN’s effects on chemotherapy treatment, and as- predisposed to more severe forms of CAPN [2–4]. sociated costs. However, Berger suggests neuropathies in gen- The chemotherapy drugs most commonly associated eral can lead to adverse outcomes and higher costs [11]. In with CAPN are taxanes (paclitaxel and docetaxel), vinca alka- particular, Berger found that patients with neuropathies had loids (vincristine and vinorelbine), and platinums (cisplatin, carboplatin, and oxaliplatin). The incidence of CAPN varies healthcare costs triple those of controls; however, the study 2 Chemotherapy Research and Practice did not examine the costs associated with chemotherapy- 2.2.1. Main CAPN Sample. Patients under age 65 were eli- related neuropathies specifically [11]. gible for inclusion in the main sample if they had at least 1 claim with a diagnosis for 1 or more of the following cancers Calhoun conducted a pilot study on the medical and from 1999–2005: NSCLC, breast, ovarian, or head and neck. workloss costs associated with chemotherapy-induced tox- The cancer types were identified using ICD-9-CM codes icities in women with ovarian cancer [12]. Using survey (see Table 1(b)). To identify NSCLC from the overall lung data on 42 patients suffering from chemotherapy-induced cancer sample, patients receiving chemotherapy regimens neurotoxicities, the study found the medical costs directly characteristic of treatment for small cell lung cancer (SCLC) attributable to CAPN were $688 per episode but that indirect were excluded. SCLC treatment was defined in this study as costs (patient and caregiver workloss and paid caregiver doublet therapy with a platinum agent in combination with costs) were over $4,200 per episode. This pilot study relied irinotecan, topotecan, or etoposide, or CCNU, melphalan, on patient recall of medical services used over 3-month and VP-16 CAV regimen chemotherapy treatments. Of the intervals. In addition, the sample was limited to women with patients with a claim for a qualifying tumor, only those with ovarian cancer and did not consider other cancer types. a procedure code indicating chemotherapy administration To the authors’ knowledge, no study has quantified the within 3 months of a claim for a qualifying tumor were comprehensive health outcomes, medical costs, and workloss selected. The date of first such chemotherapy administration burden of CAPN patients with breast, ovarian, head/neck, was considered the index date. To ensure that the index or nonsmall cell lung cancer (NSCLC). The purpose of the event marked the start of a new line of chemotherapy for current study is to assess health outcomes as well as the the tumor, patients were required to have at least 3 months healthcare (i.e., medical and drug) and workloss cost burden of continuous eligibility prior to the index date with no of CAPN patients (cases) in these 4 tumor types from a third- claims for chemotherapy. Since no specific diagnosis code party payor/employer perspective. The first objective is to exists for CAPN, the authors developed an algorithm to compare the healthcare costs of CAPN cases with those of define peripheral neuropathy (PN) using ICD-9-CM codes matched controls who have the same cancer but no CAPN. for related diagnoses and symptoms (see Table 1(b)). Any The second objective is to compare workloss costs in patients PN defined in the 9 months following the index date was with and without CAPN. The third objective is to compare assumed to be CAPN. Thus, patients were classified as the healthcare costs of CAPN cases and non-CAPN controls CAPN if they had evidence of PN within 9 months of first who have comorbid diabetes. By examining these 4 tumor chemotherapy treatment but had no evidence in the 3- types, this study captures the use of the chemotherapeutic month baseline period. Finally, for this sample, patients with agents most commonly associated with CAPN. evidence of diabetes (i.e., a diagnosis of 250.x) from at least 3 months up to 12 months prior to the index date or during 2. Methods the 12 months following the index date were excluded. 2.1. Data. Data were obtained from a database of privately 2.2.2. Diabetic CAPN Sample. A sample of patients with 1 insured administrative claims records (Ingenix Employer of the 4 tumor types, CAPN, and diabetes were selected for Database) that included approximately 8 million beneficia- the secondary analysis. The patient selection criteria were the ries from 40 large US-based companies (1999–2006). The same as in the Main CAPN sample with the exception of the companies have operations nationwide in a broad array of diabetes criteria. Specifically, diabetic CAPN patients were industries and job classifications. The database contains de- identified as those patients with a diagnosis of ICD-9-CM identified beneficiary information including demographics code 250.x anytime from at least 3 months up to 1 year prior (e.g., age and gender), enrollment, and medical and phar- to the index date or during the 12 months following the index macy claims. Utilization measures include date of service, date. diagnoses, procedures, and actual payments to providers. Pharmaceutical drug claims include National Drug Code 2.2.3. CAPN Employee Sample. A subsample of patients from (NDC), fill date, days of supply, quantity, and actual the Main CAPN and Diabetic CAPN samples who were payments. In addition, disability claims and employee wage employees with disability data were selected for the workloss information were available for employees in 23 companies. cost analysis. Note that this sample will not contain all employed persons from the main and diabetic CAPN 2.2. Sample Selection. Three analytic samples consisting of samples but rather will only include the employees of the CAPN cases and matched non-CAPN controls were used subset of companies with disability data available. for this study. The main sample, consisting of cases and controls without diabetes, was used to evaluate the healthcare 2.2.4. Study Period for All Samples. The study period encom- costs and resource use associated with CAPN patients. A passed the 12 months following the index date. Since the sample of cases and controls with diabetes was used in the perspective adopted was that of the payor and the payor secondary analysis to evaluate the costs and resource use incurs no cost for patients who withdraw from coverage, associated with diabetic CAPN patients. Finally, a subsample no requirements were placed on the length of continuous of employed cases and controls was used to assess the eligibility following the index event. The baseline period for workloss burden associated with CAPN patients. Table 1(a) assessing patient history extended 3 months prior to the presents the sample selection. index date except for ascertaining the presence of diabetes. Chemotherapy Research and Practice 3 Table 1: Inclusion criteria and ICD-9-CM codes used for analytic samples. (a) Inclusion criteria Number of patients Criteria 1 4,729,443 Number of beneficiaries under 65 at eligibility start >1 breast, ovarian, head and neck, or nonsmall cell 2 56,261 lung cancer claim from 1999–2005 >1 chemotherapy treatment within 3 months following 3 14,142 a breast, ovarian, head and neck, or nonsmall cell lung cancer diagnosis >3 months of continuous eligibility prior to the first chemotherapy treatment for the qualifying tumor 4 11,009 during which no other chemotherapy treatment was received >1 diagnosis for peripheral neuropathy following first 5 1,245 chemotherapy treatment Peripheral neuropathy within 9 months of first 6 525 chemotherapy treatment Main CAPN sample: no diabetes history Diabetic CAPN sample Employee CAPN subsample (b) ICD-9-CM Diagnosis Codes Used for Identification of CAPN and Cancer CAPN ICD-9-CM code Polyneuropathy due to drugs 357.6 Disturbance of skin sensation 782.0 Inflammatory and toxic neuropathy 357.x Toxic optic neuropathy 377.34 Reflex sympathetic dystrophy 337.2 Cervical root lesions 353.2 Lumbosacral root lesions 353.4 Other mononeuritis of unspecified site 355.7 Mononeuritis of unspecified site 355.9 Neuralgia, neuritis, or radiculitis 729.2 Brachial plexus lesions 353.0 Cancer ICD-9-CM code Nonsmall cell lung cancer 162.x Breast cancer 174.x, 175.x Ovarian 183.x Head and neck 195.0, 140.x, 141.x, 142.x, 143.x, 144.x, 145.x, 146.x, 147.x, 148.x,149.x In all cases, the patients were required to have a minimum of type, index date of chemotherapy, length of followup 3 months eligibility prior to the index date to qualify for the (controls were required to have postindex eligibility of study. at least as long as their matched case), and the estimated likelihood of developing CAPN. Each case was matched 2.3. Matching. Cases in the main CAPN sample and the 1 : 1 to a control using an optimal matching algorithm [13]. diabetes CAPN sample were separately matched to controls Likelihood of developing CAPN was derived as a propensity selected from among the set of NSCLC, breast, ovarian, score from a logistic regression model based on resource use and comorbidities during the baseline period. Specif- and head/neck cancer patients receiving chemotherapy who did not have a diagnosis for CAPN-related symptoms ically, the model included age, sex, Charlson Comor- at any time in the claims history and were under age bidity Index (CCI) [14], number of inpatient, primary 65. Controls were matched to cases based on age, gender, care, oncology, neurology, and other physician visits, and employment status (employee versus nonemployee), cancer binary variables indicating whether patient went to the 4 Chemotherapy Research and Practice emergency room or had depression or uncomplicated hyper- 2.5. Statistical Analyses. Baseline characteristics (demo- tension. graphics, comorbidities, resource use rates) were summa- rized as proportions of the sample with the characteristic. The time period over which controls contributed to Continuous measures (e.g., healthcare costs, workloss costs, the outcomes measures was truncated at the end of the resource use amount) were summarized by mean and stan- observation period for their matching case (i.e., the earlier of dard deviation. Comparisons of matched pairs of categorical either 12 months or when cases dropped from the database). variables used McNemar tests. Comparisons of the differ- ences in continuous measures between cases and controls 2.4. Measures. Healthcare costs were stratified into 3 mutu- used paired t-tests. Excess costs of CAPN cases compared ally exclusive groups: chemotherapy costs, drug costs, and with controls (i.e., costs of CAPN cases minus those of medical costs. Costs were computed as the paid (reimbursed) controls) were compared between diabetic and nondiabetic amount by the insurer to the health-care provider and patients using a 2-sample t-test. All analyses were conducted were annualized to 2006 U.S. Dollars using the Consumer using SAS version 9.1 (SAS Institute Inc., Cary, NC). P- Price Index for medical care. Chemotherapy costs included values less than or equal to 0.05 were considered statistically medical claims with a chemotherapy procedure code and significant. pharmacy claims for oral chemotherapy agents, identified by NDCs. Drug costs included all pharmaceutical claims 3. Results other than chemotherapy claims. Medical costs included claims for inpatient, emergency department (ED), and The main study sample for the healthcare cost and resource outpatient/other care. Costs included all claims associated use analysis contained 454 cases and controls without dia- with any service provided to the case/control during the betes (see Table 1(a)). The diabetes sample for the secondary study period regardless of diagnosis, procedure, or drug. analysis contained 71 diabetic cases and controls. The The subset of pharmaceutical and medical costs that could employee subsample for the workloss cost and resource use be directly attributed to CAPN was estimated as follows: analysis contained 78 cases and controls. CAPN-related drug costs included those for drugs potentially used for CAPN (i.e., amitriptyline, gabapentin, amifostine, 3.1. Baseline Characteristics. Tables 2(A) and 3(A) show the glutamine, tricyclic antidepressants, anti-epileptics, NSAIDs, baseline comparison of CAPN cases and their matched non- and opioids) and CAPN-related medical costs included those CAPN controls within the main sample. Cases and controls from claims with a primary or secondary diagnosis of a were balanced in terms of types of cancer and CCI. However, CAPN-related symptom (see Table 1(b)). CAPN cases had more congestive heart failure (4% versus Healthcare resource use consisted of hospitalizations, 2%, P = 0.0412) and uncomplicated hypertension (17% emergency department (ED), and outpatient/other services versus 11%, P = 0.0164), whereas the control group had a (reported by type of visit). The resource use components higher rate of complicated hypertension (3% versus 1%, P = were defined using provider specialty codes and/or place 0.0290). Resource use was generally the same between cases of service codes on the claims. All claims during the study and controls; however, there were more cases with neurology period were included in assessing resource use, regardless specialist visits than controls (5% versus 2%, P = 0.0482). of the underlying reason for a visit. In addition, the pro- The number of neurology visits and neurology costs were not portion of patients using CAPN-related drugs, and specific significantly different. chemotherapy agents were measured. Workloss days and costs consisted of disability and med- 3.2. Study Period Descriptive Characteristics, Healthcare Re- ically related absenteeism. Workloss costs during the 12- source Use, and Costs. CAPN cases had significantly higher month study period included actual employer payments rates and counts of comorbidities and resource use dur- for disability days plus imputed costs for medically related ing the study period compared with matched non-CAPN absenteeism. Medically related absenteeism costs were controls (Tables 4(A) and 5(A)). Significantly more cases imputed by multiplying the number of days with medical had fibromyalgia, obesity, and uncomplicated hypertension services resource use by the employee’s wage: each hospi- during the study period than their matched controls. Cases talization day accounted for a full day of workloss, and also had a higher CCI during the study period (4.7 versus outpatient visits accounted for half a day of workloss. As with 4.1, P< 0.0001). There were no differences in the classes healthcare costs, total workloss costs were not limited to only of chemotherapy agents used by cases and controls. The those related to a particular condition. most common chemotherapeutic agents used by cases and Patient characteristics included demographics, employ- controls were taxanes (33%, 28%) and platinums (20%, ment status (employee versus nonemployee), cancer type, 18%). Significantly more cases used a CAPN-related drug cancer stage (metastatic versus not metastatic), and comor- than controls (72% versus 56%, P< 0.0001). Cases had bidities identified using claims during baseline period and substantially higher rates and amounts of use of both in- the 12-month study period. Metastatic cancer was defined patient and outpatient visits during the study period. More using claims with diagnoses for metastases (ICD-9-CM codes cases were hospitalized at least once compared with controls 196.0-199.1). The CCI was calculated from the claims data (51% versus 37%, P< 0.0001). CAPN cases had significantly and individual physical comorbidities included in the index higher rates and amounts of use for all outpatient compo- which were also identified [14]. nents except for primary care visits and lab/pathology. More Chemotherapy Research and Practice 5 Table 2: Three-month baseline demographics and comorbidities of CAPN cases and non-CAPN controls. (A) Main Sample: no diabetes (B) Diabetes Sample Cases Controls P-value Cases Controls P-value No. % No. % No. % No. % N 454 454 71 71 Demographics Age (mean, SD) 53.9 7.5 53.7 9.3 0.0006 58.5 5.0 57.9 8.3 0.5044 Gender (n, % male) 69 15% 69 15% 1.0000 13 18% 13 18% 1.0000 Employment Status (n, % employed) 75 17% 75 17% 1.0000 3 4% 3 4% 1.0000 Months followup (mean) 11.1 2.2 11.3 1.7 12-month followup 366 81% 56 79% Time to CAPN (mean days, SD) 147.5 82.9 137.2 85.7 1–3 months 125 27% 22 31% 3–6 months 149 33% 26 37% 6–9 months 179 39% 23 33% Cancer type Nonsmall cell lung 82 18% 82 18% 1.000 18 25% 18 25% 1.000 Breast 316 70% 316 70% 1.000 42 59% 42 59% 1.000 Ovarian 28 6% 28 6% 1.000 7 10% 7 10% 1.000 Head and neck 27 6% 27 6% 1.000 4 6% 4 6% 1.000 Metastatic cancer 168 37% 164 36% 0.7883 33 46% 20 28% 0.0374 Comorbidities Depressive disorders 23 5% 31 7% 0.2673 2 3% 3 4% 0.6547 Congestive heart failure 20 4% 10 2% 0.0412 7 10% 8 11% 0.7963 Fibromyalgia 7 2% 7 2% 1.0000 4 6% 1 1% 0.1797 Obesity 8 2% 2 0% 0.0578 2 3% 0 0% 0.0578 Hypertension—uncomplicated 76 17% 52 11% 0.0164 22 31% 24 34% 0.7316 Hypertension—complicated 4 1% 13 3% 0.0290 4 6% 0 0% 0.0290 Other cancers 83 18% 74 16% 0.4352 17 24% 21 30% 0.4497 Charlson Comorbidity Index 4.4 4.3 0.4913 6.0 4.5 0.0043 CAPN indicates chemotherapy-associated peripheral neuropathy; SD, standard deviation. P-values are determined using McNemar tests for proportions and paired t-tests for continuous measures. cases saw a neurologist than did controls (29% versus 6%, 0.5744). CAPN-related drug and medical costs accounted for P< 0.0001). approximately 2% of total healthcare costs. Table 6(A) shows the healthcare cost comparison for cases and controls. For cases, mean annual per capita health- 3.3. Workloss and Costs. There were no statistically signif- care costs were $69,950 versus $52,606 per control, with an icant differences in workloss measures between the subset excess annual per patient cost of $17,344 (P< 0.0001). Mean of 78 employees with CAPN and their matched non-CAPN excess annual per patient healthcare costs for cases versus controls (Table 7). More cases had disability claims than controls were $36,660 for head and neck cancer, $18,790 controls (35% versus 26%, resp.). Cases also had almost twice for nonsmall cell lung cancer, $16,940 for breast cancer, as many disability days as their matched controls (37.4 versus and $5,140 for ovarian and all were statistically significant 20.4 days, resp.). While almost all cases and controls had at (data not shown). Cases had significantly higher component least 1 medically related absenteeism day (95% and 97%, costs compared with controls. Outpatient costs were the resp.), cases missed 6 additional days over the 12-month highest component for both cases and controls. However, study period compared with controls. the excess costs of outpatient and inpatient components were Averageannualworklosscosts were approximately25% similar with cases having excess annual outpatient costs of higher for cases than controls ($11,298 versus $9,043, resp.) $8,092 per patient (P< 0.0001) and excess annual inpatient with a $2,255 annual per patient difference (Table 7). Cases costs of $7,552 per patient (P< 0.0001). Annual oncology- had both higher disability and higher medically-related related costs (i.e., chemotherapy and oncologist specialist absenteeism costs than controls ($4,970 versus $3,356 for costs) were $22,453 for cases compared with $19,362 for disability and $6,329 versus $5,687 for medically-related controls, with the majority of costs being chemotherapy costs absenteeism). However, workloss cost differences were not ($16,984 and $16,169 for cases and controls, resp., P = statistically significant. 6 Chemotherapy Research and Practice Table 3: Three-month per-capita baseline resource use and healthcare costs of CAPN cases and non-CAPN controls. (A) Main Sample: no diabetes (B) Diabetes Sample a a Cases Controls P-value Cases Controls P-value No. % No. % No. % No. % N 454 454 71 71 Resource use rate Hospitalizations 204 45% 193 43% 0.4692 43 61% 33 46% 0.1138 ED visits 75 17% 68 15% 0.5139 21 30% 16 23% 0.3980 Outpatient visits 444 98% 445 98% 0.8185 71 100% 70 99% 0.8185 Oncology 188 41% 174 38% 0.3408 26 37% 30 42% 0.4795 Neurology 22 5% 11 2% 0.0482 5 7% 1 1% 0.1025 a a Resource use amount Mean (SD) Mean (SD) P-value Mean (SD) Mean (SD) P-value Hospitalizations 1.96 (5.53) 1.48 (3.21) 0.0956 3.48 (5.02) 4.10 (9.75) 0.5702 ED visits 0.24 (0.70) 0.21 (0.58) 0.3550 0.41 (0.73) 0.35 (0.76) 0.6310 Outpatient visits 11.37 (6.80) 11.25 (7.40) 0.7449 12.80 (6.08) 11.28 (6.76) 0.1420 Oncology 1.40 (3.06) 1.33 (3.47) 0.6673 1.38 (3.10) 1.44 (2.97) 0.9040 Neurology 0.06 (0.31) 0.03 (0.22) 0.0848 0.07 (0.26) 0.01 (0.12) 0.1029 Total costs $17,797 ($22,255) $17,180 ($25,240) 0.6698 $22,308 ($24,970) $21,061 ($22,748) 0.6898 Drug costs $433 ($857) $467 ($1,148) 0.6064 $800 ($868) $646 ($824) 0.2761 Medical costs $17,363 ($22,185) $16,712 ($25,140) 0.6527 $21,508 ($24,871) $20,415 ($22,636) 0.7268 Inpatient $6,496 ($19,301) $5,928 ($21,811) 0.6632 $11,220 ($22,256) $9,382 ($21,412) 0.4845 ED $127 ($826) $102 ($576) 0.6043 $125 ($290) $122 ($340) 0.9490 Outpatient $10,336 ($10,186) $10,328 ($10,282) 0.9900 $9,725 ($8,672) $10,358 ($9,840) 0.6935 Oncology $438 ($1,329) $439 ($1,796) 0.9841 $379 ($996) $431 ($1,452) 0.7989 Neurology $10 ($61) $9 ($108) 0.8812 $24 ($163) $1 ($7) 0.2435 CAPN indicates chemotherapy-associated peripheral neuropathy; SD, standard deviation; ED, emergency department. P-values are determined using McNemar tests for proportions and paired t-tests for continuous measures. Table 4: Chemotherapy agents and comorbidities of CAPN cases and non-CAPN controls during the 12-month study period. (A) Main Sample: no diabetes (B) Diabetes Sample a a Cases Controls P-value Cases Controls P-value No.%No.% No.%No.% N 454 454 71 71 Metastatic cancer 171 38% 136 30% 0.0097 30 42% 22 31% 0.1306 Classes of select chemotherapy agents used Taxanes 148 33% 125 28% 0.0978 30 42% 17 24% 0.0236 Vinca Alkaloids 18 4% 14 3% 0.4497 3 4% 2 3% 0.6547 Platinums 90 20% 80 18% 0.4014 17 24% 20 28% 0.5775 Comorbidities Depressive disorders 68 15% 50 11% 0.0804 8 11% 3 4% 0.1317 Congestive heart failure 23 5% 20 4% 0.6219 12 17% 12 17% 1.0000 Fibromyalgia 37 8% 8 2% <.0001 8 11% 1 1% 0.0196 Obesity 9 2% 2 0% <.0001 1 1% 0 0% 0.2568 Hypertension—uncomplicated 114 25% 83 18% 0.0134 33 46% 35 49% 0.7576 Hypertension—complicated 13 3% 13 3% 1.0000 5 7% 1 1% 0.1025 Other cancers 124 27% 101 22% 0.0838 20 28% 19 27% 0.8415 Charlson Comorbidity Index 4.7 4.1 <.0001 7.0 5.6 0.0052 CAPN indicates chemotherapy-associated peripheral neuropathy. P-values are determined using McNemar tests for proportions and paired t-tests for continuous measures. Other cancers include all cancers other than head and neck, breast, non-small cell lung, and ovarian. Chemotherapy Research and Practice 7 Table 5: Resource use of CAPN cases and non-CAPN controls during the 12-month study period. (A) Main Sample: no diabetes (B) Diabetes Sample a a Cases Controls P-value Cases Controls P-value No.%No.% No.%No.% N 454 454 71 71 Resource use rate Medical Hospitalizations 231 51% 166 37% <.0001 48 68% 32 45% 0.0136 ED visits 213 47% 170 37% 0.0037 42 59% 27 38% 0.0222 Outpatient visits 453 100% 447 98% 0.0339 71 100% 70 99% 0.0339 Oncology 288 63% 250 55% 0.0075 43 61% 39 55% 0.5050 Neurology 133 29% 29 6% <.0001 30 42% 5 7% <.0001 Primary care 354 78% 345 76% 0.4726 59 83% 60 85% 0.8185 Other physician 444 98% 428 94% 0.0035 71 100% 66 93% 0.0035 Lab/pathology 181 40% 160 35% 0.1540 21 30% 22 31% 0.8694 Other outpatient 400 88% 369 81% 0.0030 68 96% 61 86% 0.0522 Prescription drug use At least 1 CAPN-related drug 329 72% 256 56% <.0001 66 93% 46 65% 0.0003 a a Resource use amount Mean (SD) Mean (SD) P-value Mean (SD) Mean (SD) P-value Medical Hospitalizations 5.6 (11.69) 3.2 (7.77) 0.0001 9.1 (14.38) 6.2 (13.44) 0.2195 ED visits 1.1 (2.80) 0.6 (1.28) 0.0022 1.6 (1.98) 0.8 (1.35) 0.0064 Outpatient visits 51.3 (29.57) 39.8 (26.81) <.0001 56.9 (27.02) 38.5 (25.10) <.0001 Oncology 12.7 (18.92) 9.2 (15.55) 0.0021 12.6 (16.97) 7.5 (10.62) 0.0322 Neurology 0.6 (1.29) 0.1 (0.51) <.0001 1.1 (1.87) 0.1 (0.56) 0.0002 Primary care 6.9 (12.65) 5.0 (8.74) 0.0085 7.4 (10.25) 5.7 (5.64) 0.2454 Other physician 22.1 (21.22) 17.2 (18.82) 0.0001 25.9 (20.63) 18.6 (18.82) 0.0217 Lab/pathology 1.1 (2.62) 0.9 (2.49) 0.2127 0.8 (3.59) 1.1 (3.93) 0.6594 Other outpatient 13.6 (16.47) 11.4 (15.97) 0.0349 15.5 (15.37) 11.0 (16.56) 0.0905 CAPN indicates chemotherapy-associated peripheral neuropathy; SD, standard deviation; ED, emergency department. P-values are determined using McNemar tests for proportions and paired t-tests for continuous measures. 3.4. Secondary Analysis of CAPN and Diabetes. Tables 2(B) (P< 0.0001). CAPN-related drugs were used by 93% of cases and 3(B) show the baseline comparison of diabetic cases and compared with 65% of controls (P = 0.0003). their matched diabetic controls. Cases had more metastatic For cases, annual per capita healthcare costs were disease (46% versus 28%, P = 0.0374), complicated hyper- $76,555 versus $54,816 per control, with an excess annual tension (6% versus 0%, P = 0.0290), and a higher CCI per patient cost of $21,739 (P = 0.0273, Table 6(B)). Annual than controls (6.0 versus 4.5, P = 0.0043). Resource use oncology-related costs were $25,181 for cases compared with was generally well balanced; however, cases did have more $15,377 for controls, with the majority of these costs being primary care visits than controls (2.75 versus 1.75, P = chemotherapy costs ($20,990 and $13,033 for cases and con- 0.0136). There were no statistically significant differences in trols, resp., P = 0.0670). The diabetic case’s annual per capita baseline costs. excess costs were higher than the control’s costs ($21,739 Cases had significantly higher rates and counts of re- versus $17,344), however, this difference was not statistically source use during the study period compared with controls significant. (see Tables 4(B) and 5(B)). More cases than controls used taxanes (42% versus 24%, P = 0.0236). More cases were 4. Discussion hospitalized compared with controls (68% versus 45%, P = 0.0136) though the days per capita were not statistically This study is the first to use claims data to estimate the excess different (9.1 versus 6.2 for cases and controls, resp., P = costs of CAPN patients in breast, nonsmall cell lung, ovarian, 0.2195). Six times as many cases had a neurology specialist and head and neck cancer over a matched sample of cancer visit during the study period compared with controls (42% patients without CAPN. This study also included a secondary versus 7%, P< 0.0001). Cases also had 18.4 more outpatient analysis to examine the excess costs of CAPN patients among visits during the study period on average than the controls patients with comorbid diabetes. 8 Chemotherapy Research and Practice Table 6: Per capita healthcare costs for CAPN cases and non-CAPN controls during the 12-month study period. (A) Main Sample: no diabetes (B) Diabetes Sample a a Cases Controls P-value Cases Controls P-value mean (SD) mean (SD) mean (SD) mean (SD) N 454 454 71 71 Total healthcare costs $69,950 ($66,913) $52,606 ($55,554) <.0001 $76,555 ($63,379) $54,816 ($68,115) 0.0273 Chemotherapy costs $16,984 ($21,248) $16,169 ($27,055) 0.5744 $20,990 ($31,501) $13,033 ($19,725) 0.0670 Drug costs $3,744 ($5,333) $3,071 ($4,927) 0.0419 $6,017 ($7,461) $4,223 ($6,100) 0.1163 CAPN-related drugs $595 ($1,590) $328 ($1,041) 0.0016 $718 ($1,401) $371 ($782) 0.0832 Medical costs $49,223 ($56,500) $33,366 ($36,931) <.0001 $49,548 ($46,428) $37,561 ($57,723) 0.1614 Inpatient $14,050 ($35,793) $6,498 ($15,558) <.0001 $19,181 ($38,190) $15,148 ($44,098) 0.5637 ED $474 ($1,093) $263 ($730) 0.0005 $798 ($1,817) $243 ($535) 0.0172 Outpatient $34,698 ($36,712) $26,606 ($29,913) <.0001 $29,569 ($21,339) $22,170 ($29,244) 0.0921 Oncology $5,469 ($15,923) $3,193 ($8,478) 0.0072 $4,191 ($6,950) $2,344 ($4,729) 0.0554 Neurology $129 ($319) $46 ($433) 0.0011 $326 ($843) $44 ($278) 0.0103 Primary care $7,772 ($12,454) $6,543 ($9,920) 0.0979 $6,024 ($7,341) $4,472 ($5,965) 0.1252 Other physician $7,437 ($13,782) $6,804 ($17,452) 0.5247 $6,235 ($11,447) $5,150 ($16,025) 0.6502 Lab/pathology $414 ($1,825) $289 ($1,490) 0.2632 $485 ($2,027) $110 ($193) 0.1237 Other outpatient $13,476 ($24,509) $9,731 ($18,345) 0.0064 $12,307 ($16,297) $10,049 ($20,812) 0.4798 CAPN-related medical costs $725 ($2,005) $491 ($762) CAPN indicates chemotherapy-associated peripheral neuropathy; SD, standard deviation; ED, emergency department. P-values are determined using McNemar tests for proportions and paired t-tests for continuous measures. Table 7: Per capita workloss days and costs during the 12-month The results suggest that CAPN patients are associated study period. with a significant and substantial economic burden among the privately insured U.S. population. Cases with CAPN had Employee subsample on average $17,344 higher healthcare costs during the 12- Cases Controls P-value month study period compared with controls without CAPN. Compared with controls, more cases were hospitalized, had No. % No. % an emergency department visit, saw an oncologist or neu- 78 78 rologist, and had other outpatient visits. In addition, each Workloss rate case with CAPN averaged 12 more outpatient visits and spent more days in the hospital. This suggests that in addition to Medically 74 95% 76 97% 0.4142 related the excess cost burden to third-party payors, the patients absenteeism themselves may (depending on their insurance benefits) experience a large burden in terms of out-of-pocket costs 27 35% 20 26% 0.2367 Disability (e.g., copayments, coinsurance) and time spent on medical mean (SD) Mean (SD) P-value Workloss days care. Medically CAPN can lead to increased costs as a result of services 31.5 (28.1) 25.3 (18.2) 0.0573 related specifically aimed at mitigating the PN (e.g., increased physi- absenteeism cian visits to monitor the PN, costs of PN treatment) and sec- 37.4 (75.4) 20.4 (50.8) 0.1048 Disability ondary effects, such as switches in chemotherapy regimens mean (SD) mean (SD) P-value or exacerbated cancer. This study separately estimated the Workloss costs costs for CAPN-related services and found they accounted Total employer $11,298 ($11,830) $9,043 ($12,416) 0.2161 for less than 2% of healthcare costs during the 12-month costs study period. While a significantly higher proportion of Medically CAPN patients did use the pharmacologic treatments used $6,329 ($7,136) $5,687 ($6,200) 0.5012 related to manage neuropathic symptoms, these drugs are often absenteeism generic or lower cost relative to cancer treatments and $4,970 ($10,994) $3,356 ($10,284) 0.3134 Disability overall healthcare costs. CAPN-related medical costs were SD indicates standard deviation. low suggesting that the excess utilization demonstrated by P-values are determined using McNemar tests for proportions and paired cases was not directly attributed to CAPN. However, the t-tests for continuous measures. CAPN-related costs as measured here may understate the Workloss rate defined as the number of people with ≥1 disability claim or ≥1 instance of medically-related absenteeism. true burden related specifically to CAPN. First, because there Chemotherapy Research and Practice 9 are no specific diagnoses for CAPN, PN-related diagnoses confounding factors not available in this database. Moreover, may be underreported on claims. In addition, the secondary because CAPN does not have a specific diagnosis code and is effects of CAPN mentioned above are not included in the not consistently recorded in claims data, there are challenges CAPN-related subset of costs presented here but rather are in identifying the condition. Physicians may not report included in the chemotherapy, drug, and medical costs. CAPN unless the impairment is severe enough to affect a Overall, this study finds that patients with CAPN expe- patient’s activities of daily living or warrant alterations to rience significantly increased costs and resource use. It is cancer treatment [1]. Thus, this study may include more important not to conclude that all of the excess costs are severe cases of CAPN and may have under identified CAPN caused by CAPN. Since the cases and controls were matched patients. The algorithm used for identifying CAPN in this during the baseline period, the results suggest that CAPN study has not been validated. It is possible that the PN is a serious condition that should be carefully monitored identified was due to other causes. Another study limitation in clinical practice. Improvements to the diagnostic tools is that due to data availability, cases and controls are matched for CAPN severity and investigation of therapies that treat using only 3 months of baseline data and information on CAPN without negatively impacting the cancer treatment cancer stage beyond metastatic/nonmetastatic is not avail- could benefit both patients and payors. able. A longer baseline period using a larger database with Calhoun’s pilot study of chemotherapy-induced toxicity clinical information on cancer stage may allow for additional found that the direct CAPN costs for women with ovarian controls. The lack of restrictions on the length of continuous cancer are $688 for episodes up to 9 months, compared with eligibility following index date is another possible limitation. our findings that CAPN-related costs are on average $1,320 This limitation could potentially lead to censoring of costs if over a period up to 12 months [12]. Calhoun’s study relied a patient’s plan were to have withdrawn from the database on patient reported utilization and standard fee data whereas while the patient was continuing to incur costs; however, no data here are actual reimbursements, which may, in addition such instances occurred in the study and the average length to the difference in length of followup, explain the differences of followup for patients in the study is 11.1 months. Finally, in estimates. Calhoun also analyzed indirect costs based small sample sizes, particularly in the head and neck, ovarian, on national labor force, employment, and earnings data, workloss cost, and diabetic analyses, limited both the types including patient workloss, caregiver workloss, and paid of comparisons as well as the robustness of the statistical caregiver costs. Calhoun found indirect costs were $4,220, inferences. Though this study reports directional differences with 67% of that due to caregiver workloss. Patient workloss in workloss outcome measures, no significant differences costs were $620 per patient per episode compared with our were found, potentially due to the small sample size. findings of $642 per patient per year in excess medically related absenteeism costs. Though Calhoun did not include 5. Conclusion disability costs, this study found CAPN patients had mean excess per patient per year disability costs of $1,614. While CAPN patients are associated with significantly higher the workloss findings were not statistically significant, this healthcare costs and resource use in patients with breast, may be due to the small sample size. It is important to ovarian, head/neck, or NSCLC. The excess healthcare cost note that the workloss cost estimates reported in this study of CAPN is underestimated when only the cost for med- may differ from actual employer costs depending on the ical or pharmacy claims directly for CAPN is considered. employer’s paid time off policies. Improvements in clinical assessments and treatments for Healthcare costs and resource use were calculated for CAPN would be useful for patients and payors. diabetic CAPN patients as a secondary analysis as literature suggests that diabetes may exacerbate the risk and severity of CAPN. With the prevalence of diabetes increasing, it is Acknowledgments important to assess how diabetic CAPN patients may differ from controls and nondiabetic CAPN patients. The results R. B. Natale of Cedars-Sinai Medical Center, Los Angeles, demonstrated that diabetes may, indeed, be associated with CA, USA served as a clinical consultant to the study. The increased cost in patients with CAPN, as excess costs of authors would like to thank Rebecca Kaufman for her diabetic CAPN patients were 25% higher than for nondi- assistance with this study. Previous presentations of this abetic CAPN patients. However, the comparison between study are as follows: C. T. Pike, H. G. Birnbaum, R. J. diabetic and nondiabetic CAPN patients was not statistically Kaufman, C. E. Muehlenbein, G. M. Pohl, R. B. Natale, significant, perhaps due to the small sample of diabetic direct healthcare and workloss burden of chemotherapy- CAPN patients. In addition, although diabetic cases were associated peripheral neuropathy in breast, ovarian, head balanced with their controls in terms of costs and resource and neck, and nonsmall cell lung cancer; value Health 2009; use, a higher proportion of cases had metastatic cancer and 12(3):A1-A19. Oral Presentation ND2 at ISPOR 14th Annual the CCI of cases was significantly higher than controls. Both International Meeting, 16–20 May 2009, Orlando, Florida, these factors could impact the excess cost findings. United States. This study was sponsored by Eli Lilly and This study is limited by the lack of clinical measures, Company, Indianapolis, IN, USA. C. Muehlenbein and G. which is common to research that uses claims data. While M. 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