For persons who suffer from pain, the difference between the covered and market price represents a potentially meaningful burden, which increases with the duration of analgesic therapy. The difference is greater with branded medications, extended release medications, and larger quantities. Although we find little evidence that differentiates opioid analgesic prices between older and all adults, US prices, and particularly market prices, tend to vary across region and time, creating differential economic barriers to pain management.
Instead of prices, health policy debates have focused largely on generic entry, either through patent expiry or importation, and drug insurance coverage. The promotion of generic availability and expanding the number of insured individuals is meaningless if these actions do not lower the economic barriers to needed care, such as pain management. The value of health insurance is not that it insures health, but that insurance is intended to insure access to care and relief from financial burden of out-of-pocket costs. In this paper, we show that insurance increases the likelihood of paying the covered price for opioid analgesic medications (by over 500%), still many prescriptions (about 15%) for insured individuals were not covered.
With the recent implementation of the Medicare Part D prescription drug benefit, the effect of insurance on out-of-pocket prices may take the center stage in the evaluation of health policy, particularly in older adults. For example, among persons not previously enrolled in a prescription drug insurance benefit, Medicare Part D may reduce costs, at least for drugs covered within their benefits formulary. On the other hand, many older adults may fall into the doughnut hole, or be shifted out of a more generous employer-based plan into Medicare D, resulting in increased drug prices. Instead of promoting coverage, importation of cheaper drugs or expediting generic entry may lower market prices, reducing out-of-pocket prices among those who lack coverage.
Generic entry (i.e., when an alternative firm is first approved to sell a generic version of the drug) increases competition, which can lower prices; however, competition from a single generic manufacturer causes a very small reduction in market prices (about 5%).(44
) By law, the first generic manufacturer to get FDA approval is granted a 180 days exclusivity period, prohibiting further generic entry during this period. Market exclusivity with one brand and one generic manufacturer tends to maintain the market price at near-monopolistic levels. At the end of the exclusivity period, if at least one or more generic manufacturers enter the market, market prices decrease by 52% or more, depending on the number of generic entrants. The markets for two of the eight opioid analgesic medications experienced generic entry between 1999 and 2004: immediate-release tramadol (June 19, 2002) and extended-release oxycodone (March 24, 2004). However, the market price of extended-release oxycodone changed little over 2004, due to the generic exclusivity period, and subsequent withdrawal of generic controlled-release oxycodone. Furthermore, too few data points were available in the MCBS and MEPS samples to adequately distinguish a drop in the 2004 immediate-release tramadol market price, and the data did not distinguish generic from branded medications. To address this limitation, future work may examine the effect of generic entry on market prices experienced by the insured and uninsured.
Aside from health policy, prices are clinically important for several reasons. Kennedy and Morgan have found that chronic pain is itself predictive of non-adherence.(45
) The effect of inadequate coverage of opioid analgesics may deter effective pain management and indirectly deter adherence to other therapeutic regimens. High market prices may also influence the choice between opioid analgesics, favoring generic medications over branded extended-release formulations. Specifically, combinations consisting of acetaminophen (APAP) accounted for around two-thirds of prescribed opioid analgesics within these samples, and present important clinical challenges. While opioid doses can be increased to provide more analgesia, the dose ceiling for acetaminophen is relatively low, due to the potential for toxicity. As a result, use of APAP combinations impedes dosing flexibility.
To further complicate this picture, the clinical utility of codeine and propoxyphene are limited by the pharmacologic profile of these drugs. Codeine is a prodrug, which must be converted to morphine in order to provide any analgesia, and bioconversion of codeine to morphine is known to be subject to pharmacogenetic variation. As a result, some individuals who use codeine will get no pain relief, yet may still experience adverse effects. In combination with 650 mg acetaminophen, analgesia from single doses of propoxyphene (65 mg of the hydrochloride or 100 mg of the napsylate form) was similar to that seen with 1000 mg APAP or 200 mg ibuprofen, and less than that from ibuprofen 400 mg or diclofenac 50 mg.(46
) Additionally, propoxyphene has an active metabolite, norpropoxyphene, which is potentially toxic, and which can accumulate in persons with diminished renal function.(47
) Furthermore, propoxyphene use is commonly discouraged as a choice for analgesia in older persons in clinical practice guidelines.(48
) Yet, in this analysis, propoxyphene accounted for 24% of events among older adults, and 14% of events among all adults. It is not clear why propoxyphene use was so common, given the strong evidence against it. This observation suggests that high prices for opioid analgesics may not only result in inadequate pain management, but may also promote use of cheaper, more toxic alternatives.
Limitations of this study primarily concern the measurement of prices. If a person decides not to get a prescription or not to fill a prescription due to high prices, the prices are not recorded in any survey. This is a form of decision-based censoring, and limits the generalizability of the results. As a result, the mean out-of-pocket prices may seem lower than conventional expectations. An optimal study would describe the out-of-pocket prices faced by all individuals who would benefit from opioid analgesics. Instead, we described the burden borne by those who get opioid analgesics, not the economic barriers faced by those who should get them.
Furthermore, the inability to quantify out-of-pocket costs over time, inability to analyze monthly opioid cost by patient characteristics (e.g., diagnosis, adjuvant analgesics), and the inability to quantify cost for an individual patient – in other words, one patient might have paid for two oxycodone with APAP prescriptions and three long-acting morphine dosage forms within the same month. Therefore, the out-of-pocket costs presented may under represent the actual costs these patients incur on a monthly basis.
This is the first paper to describe the out-of-pocket prices of common opioid analgesics, one of the most common categories of medications used in ambulatory care. Alternative sources of price data are either anecdotal (e.g., internet drugstore prices) or based on manufacturer’s advertising or published list price to wholesalers (i.e., Wholesale Acquisition Cost). In 2001, the Inspector General of the Department of Health and Human Services (HHS) recognized that the average wholesale price is “a list price reported by the drug manufacturers that is neither average nor wholesale and bears little or no resemblance to the actual wholesale prices available to physicians and suppliers who participate in the Medicare program.”(49
) A growing literature is critical of physicians, because they are largely uninformed about the drug prices faced by patients.(50
) Until more published evidence on the out-of-pocket prices is available, this criticism of physicians and health policy makers seems unfair.