Objective: To examine, in routine practice, the effectiveness and cost-effectiveness of oxycodone (OxyContin®) compared with standard therapy for osteoarthritis pain.
Study Design: Open-label active-controlled randomized naturalistic 4-month study of oxycodone vs a combination of oxycodone-acetaminophen (Percocet®).
Methods: Outcomes and health resource utilization data were collected by telephone interview. Effectiveness was measured among 485 patients as the proportion having at least 20% improvement from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index pain score. Quality-adjusted life-years (QALYs) were calculated from the Health Utilities Index 3 score. Cost-effectiveness was measured as cost per patient improved and the QALYs gained, using generic oxycodone-acetaminophen in the base case for the healthcare and societal perspectives. Uncertainty was evaluated using multiple 1-way sensitivity analyses and cost-effectiveness acceptability curves.
Results: Improvement occurred in 62.2% of patients with oxycodone and in 45.9% of patients with oxycodone-acetaminophen (P < .001). After adjustment for baseline differences, 0.0105 QALYs were gained with oxycodone compared with oxycodone-acetaminophen (P = .17). The mean societal costs per patient during 4 months were $7379 and $7528 for oxycodone and oxycodone-acetaminophen, respectively (P = .33). Oxycodone was more effective and less costly than oxycodone-acetaminophen based on the societal perspective (including costs associated with time lost). Based on the healthcare perspective (excluding costs associated with time lost), the cost-effectiveness of oxycodone was $4883 per patient improved and $75 810 per QALY gained. The base-case results were robust.
Conclusions: From the societal perspective, oxycodone was more effective and less costly than oxycodone-acetaminophen. From the healthcare perspective, oxycodone (compared with generic oxycodone-acetaminophen) fell within the acceptable range of cost-effectiveness between $50 000 and $100 000 per QALY gained.
(Am J Manag Care. 2006;12:205-214)
Osteoarthritis (OA) affects approximately 21 million people in the United States and is associated with a significant burden in terms of morbidity and costs.1 Persons with moderate-to-severe OA may experience significant disability, reduced productivity, and an overall decrease in quality of life (QOL).2-4
Most patients seek medical treatment because of the symptomatic chronic pain associated with moderate-to-severe OA. The main goal of OA therapy is to control chronic pain. The American College of Rheumatology recommends a progressive approach to oral analgesic therapy in patients with OA based on pain intensity, disease stage, and risk of medication toxicity. Prescription nonsteroidal anti-inflammatory drugs (NSAIDs), including coxibs, are recommended for moderate-to-severe OA. However, there is evidence that chronic use of NSAIDs may be associated with significant gastrointestinal and renal toxicity and with serious cardiac events.5-9 In 2004, rofecoxib (Vioxx®) was withdrawn from the market because of an increased incidence of myocardial infarction and stroke associated with its use.10 In patients for whom NSAIDs are ineffective or who are at high risk of chronic pain, the American College of Rheumatology11 and the American Geriatrics Society12 recommend stronger analgesic treatment with opioids. OxyContin® is a controlled-release brand of oxycodone that has been shown to decrease moderate-to-severe pain in patients with malignant and chronic nonmalignant conditions, including OA13,14 (Unpublished data, February 11, 2000, Marcie E. Strauss, MPH).
The efficacy of oxycodone has been shown in controlled clinical trials. However, health system decision makers increasingly require evidence of effectiveness in routine practice settings and of cost-effectiveness. No previous studies were identified that examined the cost-effectiveness of oxycodone. Given that oxycodone is an approved and widely used treatment, this study was designed to compare oxycodone treatment with the standard treatment of a combination of oxycodone-acetaminophen (Percocet®) in a routine practice setting that included health resource utilization in the treatment of OA pain. To respond to the interests of diverse audiences, including clinicians and third-party payers, we examined the cost-effectiveness results from the societal and healthcare system (HCS) perspectives.
Study Design and Patient Population
This study was a multicenter open-label randomized naturalistic 4-month parallel-group design of the analgesic effectiveness of oxycodone every 12 hours vs oxycodone-acetaminophen as needed. Patients with moderate-to-severe pain from OA of the hip or knee received a platform of usual care. Patients were recruited from 50 sites across all census regions of the United States. The study included patients =40 years of age with OA of the hip or knee for at least 3 months who experienced moderate-to-severe OA pain that was not adequately controlled with short-acting opioid therapy. Osteoarthritis history in the most affected joint had to be documented by referral from the patient's primary care physician or by medical history and physical examination completed by one of us (CC), including radiologic evidence of OA within the past 2 years. Four to 7 days before randomization, patients had to have taken 2 or more tablets of a short-acting opioid per day (equivalent daily dose of =10 mg of oxycodone) for moderate-to-severe OA pain. Data were collected at the physician's office at baseline and at study termination (month 4).
Usual care generally included prescription medications (except for long-acting opioids), over-the-counter analgesics, herbal supplements or medications, nonpharmacologic interventions (eg, massage and biofeedback), non-protocol-mandated physician visits, and hospitalizations. Alterations in usual care could be made during the course of treatment, but no long-acting opioids other than the study medication could be prescribed except for indications other than OA pain (eg, dental procedures) for a period of less than 7 consecutive days, with only 1 such period during the study. Subjects had to remain on study medication as their primary opioid agent for OA pain. All subjects continued to have access to NSAID therapy, and subjects in the oxycodone group received immediate-release 5-mg capsules of oxycodone every 4 to 6 hours as needed (=15 mg/d), as prescribed by one of us (CC) as rescue medication. Subjects in the oxycodone-acetaminophen group who were receiving a total daily dose of 4 g of acetaminophen (ie, 12 tablets of oxycodone-acetaminophen per day, or fewer if using analgesics containing acetaminophen) were eligible to receive immediate-release 5-mg capsules of oxycodone as rescue medication at the discretion of the prescriber.
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Likert 3.0 and the Health Utilities Index 3 (HUI3) health-related QOL (HRQOL) instruments were administered at baseline and at months 1, 2, 3, and 4 by telephone interview using a Web-based case report form. The WOMAC Likert 3.0 is a self-administered disease-specific HRQOL instrument with a total score and 3 subscale scores (pain, stiffness, and physical functioning).15 For the cost-effectiveness analysis (CEA), effectiveness was measured as the proportion of "patients improved," defined per the American College of Rheumatology16 guidelines as a 20% improvement in the WOMAC pain score in the study hip or knee from baseline to month 4.
Most OA trials measure HRQOL using the WOMAC scale (an OA-specific HRQOL instrument). However, the WOMAC scale does not provide a unidimensional generic preference-based measure of HRQOL that can be used in cost-utility analyses (CUAs). Consequently, the HUI3, which is such a generic instrument, was included in this study.
The HUI3 was used to measure the following 8 attributes of HRQOL: vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain/discomfort.17 The instrument provides an overall utility score (range, -0.36 to 1.00), with 0.00 indicating death and 1.00 indicating perfect health. The overall HUI3 utility score is used for calculating quality-adjusted life-years (QALYs) for the CUA.
Health Resource Utilization and Costing
Health resource utilization data (related to OA pain only) were collected by telephone interview using a Web-based case report form at weekly intervals, including medications, healthcare providers, hospitalizations and emergency department visits, diagnostic tests and procedures, home healthcare services, assistive devices, and time lost from paid work activities and from unpaid regular activities for the patient, family, and friends.
All resource utilization was costed using US prices and reimbursement rules. The market price of oxycodone in the United States in 2003 was $1.3439 per 10-mg tablet.18 Medications were costed using the 2003 Drug Topics Red Book18 mean wholesale price. The generic cost of oxycodone-acetaminophen was used in the base-case analysis. Medical devices, equipment, prosthetics, and orthotics were costed using durable medical equipment fee schedules.19 The costs of all physician and clinic visits, healthcare professional consultations, and telephone contacts were estimated based on the unadjusted payment schedule for the service rendered as set forth in the Medicare Resource-Based Relative-Value Scale.20 Costs of procedures and diagnostic tests were estimated using the global Medicare fee payment for nonfacilities as set forth in the Medicare Resource-Based Relative-Value Scale.20 Hospital emergency department or urgent care center visits were costed using estimates by Williams.21 Home healthcare services were costed using estimates from the home health prospective payment system rates paid by Medicare.22-24 Costs of time lost from activities were valued using the mean hourly earnings in 2001 from the labor force, employment, and earnings from the Statistical Abstracts of the United States.25 Time lost from work and time lost from normal activities and from unpaid regular activities for family and friends were valued equally for all aspects of time lost. All costs were adjusted to 2005 US dollars using the Consumer Price Index for medical care.26
Analyses were undertaken from the HCS and societal perspectives. The HCS perspective included costs for medications (prescription, over-the-counter, and herbal medications), healthcare visits (physician, nurse, and specialist visits), hospitalizations and emergency department visits, diagnostic tests and procedures, home healthcare services, and assistive devices. The societal perspective also included time lost from paid work and unpaid regular activities for the patient and family and friends.
The CEA compared the costs and outcomes of treatment with oxycodone with those of treatment with oxycodone-acetaminophen, estimated as the cost per patient improved. The CUA estimated the cost per QALY gained, derived from the area under the curve analysis of the HUI3 scores during 4 months, after adjustment for baseline differences.