The story of extended-release oxycodone, marketed as OxyContin, is informative and unique. Although the United States has experienced several waves of widespread prescription drug abuse over the past 150 years, the rapid ascent of OxyContin from market entry to miracle drug for chronic pain to a demonized substance of abuse and diversion on a vast scale is without precedent. Multiple factors facilitated this phenomenon. OxyContin contains a larger amount of high-potency opioid than short-acting opioid formulations. The delayed-release mechanism was easy to circumvent by chewing and swallowing or by crushing the pill and then injecting or snorting the powder. This produced a rapid, powerful opioid effect on par with heroin. Large profits were also possible from illicit sales of OxyContin, which generally commanded a black-market value of $1 per milligram (with higher prices in more rural areas) [50]. In addition, the original product labeling warned against crushing the tablets because rapid release of a potentially toxic amount of oxycodone would ensue, alerting abusers on how to best achieve maximum drug effect. The original labeling also included the FDA-condoned statement that the extended-release (ER) mechanism of OxyContin presented a lower abuse potential than other oxycodone products. Perhaps most importantly, its release coincided with the growing acceptance of opioids in pain treatment and the aggressive sale and marketing tactics of its producer, Purdue Pharma [43,50].

The timing of product launch was fortuitous. Until the 1990s, Schedule II opioids were primarily limited to use in operating rooms and inpatient settings because they required intravenous or intramuscular administration. This posed a serious obstacle to patients with chronic pain who required high-potency opioids. In response to the increasingly permissive climate and by genuine unmet patient need, several high-dose ER formulations of pre-existing opioids were introduced to market. MS Contin, an ER version of morphine sulfate, was introduced in 1985 but was primarily limited to use in cancer pain, partially a result of the stigma surrounding morphine. OxyContin was introduced in late 1995, at the point in time when prescriber attitudes were shifting from fearing iatrogenic addiction to developing a sense of security with prescribing opioid analgesics [43].

To help ensure product success, innovative approaches were employed to elevate visibility and encourage OxyContin prescribing, as well as highly aggressive marketing and sales tactics. The amount of money spent in promotion, marketing, and sales was unprecedented for an opioid, exceeding $200 million in 2001 alone [50]. Marketing and promotion efforts and the timing of the product launch resulted in a tenfold increase in OxyContin prescribing and sales revenue in just three years' time (Table 6).

In addition to the usual doctor-directed ads in medical journals, a novel indirect marketing campaign involving "nonbranded education" was implemented. Direct-to-consumer advertising of opioid drugs was prohibited, so the concept of pain relief from opioids was promoted to consumers without explicit mention of OxyContin. The public-education program Partners Against Pain (PAP) was launched, with videos, patient pain journals, and an elaborate website that marketed (to prescribers and patients) the message that pain was widespread and treatable with opioid analgesics [43,51]. The FDA later stated that the PAP website did provide information about OxyContin specifically and also contained a "Find a Doctor" feature to link consumers to physicians in their geographic area known to be willing to prescribe OxyContin [43].

More than 40 national pain-management and speaker-training conferences were conducted between 1996 and 2001. Thousands of prescribers attended the all-expenses-paid symposia held in resort locations [50]. From 1996 to July 2002, more than 20,000 pain-related educational programs and continuing medical education offerings for prescribers were funded by pharmaceutical sponsorship or financial contribution. This included a program that educated hospital physicians and staff on hospital and postoperative pain treatment compliance with Joint Commission pain standards. Pharmaceutical funding was used to underwrite the cost of the Joint Commission pain management educational programs, including the distribution of educational videos and a book on pain management (sold on the Joint Commission's website) [50]. Pharmaceutical funding has also paid for websites that provided free continuing medical educational on pain management; numerous pain management websites; groups such as the American Chronic Pain Association, the AAPM, and the APS; and a youth-focused website [43].

In 1999, pharmaceutical sales representatives were reportedly given 14,000 copies of a promotional video for physician distribution. Physicians were instructed to encourage patient viewing in their waiting rooms or as a "check-out" item and to use the video as an educational tool for office or hospital staff. The FDA later stated they were not provided the video before distribution for detection of inaccurate or unfounded claims, of which they later found several examples [43]. A patient starter coupon program was initiated that provided patients with a free limited-time prescription. Roughly 34,000 coupons had been redeemed when the program ended in 2001 [43,50].

Between 1996 and 2000, the internal sales force of the pharmaceutical firm that produces OxyContin grew from 318 representatives to 671, and a bonus system was implemented to encourage OxyContin sales [50]. The company is said to have maintained an active database containing nationwide profiles of individual physicians and their prescribing patterns, allowing for the identification of high-end and low-end OxyContin prescribers by zip code, county, and state; practices with large numbers of patients with chronic pain; and high prescribers of the company's older product MS Contin [50]. Sales representatives were reportedly directed to high opioid prescribers in their sales territories, with the goal of expanding the primary care OxyContin prescribing base. Sales representatives were also directed to call on oncology nurses, consultant pharmacists, hospices, hospitals, and nursing homes [43].

In 1996, the majority of ER opioid prescriptions went to cancer patients, but by 2000, only 3% of OxyContin prescriptions came from oncologists [52,53]. Opioid medications, and OxyContin in particular, had been successfully promoted as the first-line therapy for an increasingly wide range of moderate-to-severe pain conditions. Family practice physicians became the largest group of OxyContin prescribers, accounting for 21% of prescriptions in 2000 and close to 50% in 2003 [50,51]. This was followed by the growing concern that, in a managed care system, time constraints imposed on primary care physicians did not allow sufficient time to evaluate and follow patients with complex chronic pain [50].

The most critical issue and source of greatest prescriber concern was the risk of iatrogenic addiction. To help counter this perception, promotion and marketing to healthcare professionals and patients alike emphasized that OxyContin prescribing carried little risk of addiction. Misrepresenting this risk proved costly. In 2007, the pharmaceutical company paid $634 million in fines following guilty pleas from three of its executives to criminal charges for promoting false claims that OxyContin was less addictive and less subject to abuse and diversion than other opioids [50].

The escalating rates of OxyContin misuse were integral to the growing nationwide problem of prescription opioid abuse, diversion, addiction, and overdose. By 2004, OxyContin had become the most prevalent prescription opioid abused in the United States. Predictably, this public health epidemic created a backlash from regulatory and law enforcement agencies [54].