Opinion ID: 857139
Heading Depth: 3
Heading Rank: 1

Heading: Neurontin's Effectiveness for Off-Label Uses

Text: As the district court noted, Aetna presented studies showing that Neurontin was not more effective than a placebo in treating certain off-label indications. These studies included: four clinical studies regarding bipolar disorder, Neurontin Coordinated SJ, 677 F. Supp. 2d at 489; six clinical trials regarding neuropathic pain, id.; four clinical trials regarding nociceptive pain, id. at 490; three studies regarding migraine, id.; and three clinical trials regarding doses above 1800 mg per day, id. at 490-91. B. Defendants' Marketing of Neurontin for Off-Label Uses Beginning in late 1995 and early 1996, Parke-Davis, a subsidiary of Warner-Lambert, began marketing Neurontin as an effective treatment for bipolar disorder and other mood disorders, neuropathic and nociceptive pain, migraines and other headaches, and doses above 1800 mg per day, though the FDA had not approved Neurontin for these off-label uses. These marketing efforts continued after Pfizer purchased Parke-Davis in 2000, through at least 2001, and are described in Kaiser, slip op. at 8-9. -6- As the district court stated, Aetna presented evidence that Defendants communicated half truths that are actionable under the RICO statute in conducting this marketing, including by suppressing negative information while submitting for publication in monographs positive information about off-label indications. Neurontin Coordinated SJ, 677 F. Supp. 2d at 492; see also id. at 495, 498-99. Pfizer does not argue to the contrary on appeal. C. Defendants' Targeting of Third-Party Payors (TPPs), Including Aetna Defendants' efforts to promote Neurontin, for both onlabel and off-label uses, demonstrated their understanding that TPPs, including Aetna, would both play a role in determining demand for Neurontin (by managing access to formularies, or lists of drugs for which TPPs would pay) and ultimately pay for most prescriptions of Neurontin. In 1993, Parke-Davis listed Aetna as the number four managed care plan it intended to target to encourage the use of Neurontin as an anticonvulsant. In 1994, Parke-Davis commissioned a survey of the pharmacy directors of ten managed care plans, including Aetna. This study concluded that these plans, including Aetna, were unlikely to place formulary restrictions on anticonvulsants. A 1998 Parke-Davis business plan stated that, [i]n general, formulary access is not an issue for Neurontin so share building programs can be carried out unrestricted. Pfizer prepared a marketing business plan regarding Aetna in 2002 that -7- noted that Pfizer's sales representatives have open access to the providers in Aetna's network. That same year, Pfizer established a Neurontin Outcomes Research Task Force that sought to support the marketing of Neurontin for neuropathic pain and to prepare for a more vigorous defense of reimbursement to managed care plans. In 2003, as Neurontin's patent neared expiration, defendants commissioned a study by a market research company of how TPPs would react to a new tablet form of the drug intended to compete with generic forms of the drug. The market research company conducted focus groups with TPP representatives, including representatives from Aetna. Pfizer prepared HMO Opportunity Reports for Neurontin that tracked formulary status, projected annual sales and prescriptions, potential profits, and market share for various HMOs, including Aetna. Pfizer also tracked sources of revenue for Neurontin sales; in 2001, Pfizer recorded that 69% of its Neurontin revenues came from TPPs. D. Aetna's Decision to Pay for Neurontin Prescriptions Aetna, a large TPP, provides health payment benefits to more than 13 million people across the country. Aetna added Neurontin to its formulary -- a list of drugs it agreed to pay for under its member contracts -- soon after the FDA approved Neurontin in 1993 for use as an add-on therapy in the treatment of epilepsy. Aetna had a formulary development team comprised of pharmacists who developed clinical reviews of drug classes to -8- present to Aetna's Pharmacy and Therapeutics Committee (P & T Committee). These reviews presented all the clinical information available to Aetna about a drug class, and included all the drugs within a class used for a particular therapeutic purpose. The formulary development team looked at package inserts, drug compendia, and online collections of clinical research, and also met with drug manufacturers to get information that had not been published. Aetna's P & T Committee met monthly to determine what would be included on formularies, as well as appropriate coverage restrictions on drug classes, by majority vote. The Committee reviewed clinical drug reviews, previous clinical policy bulletins the Committee had issued, and any other formulary documents (such as formulary guides disseminated to doctors). The Committee considered the safety, efficacy, on-labeled indications, and off-label indications of drugs, as well as cost information and the other drugs within a class. To control drug prescriptions, Aetna used formulary controls and mailings to physicians. Aetna initially decided not to place formulary restrictions on the anticonvulsant drug class, which included Neurontin. In late 2003, however, Aetna decided to manage the class of anticonvulsants because it wanted to encourage the use of first-line monotherapy drugs. Neurontin was moved to non-preferred status. That is, Aetna imposed quantity (i.e., -9- dose) limits on Neurontin prescriptions in 2004, and step edits (under which other drugs needed to be tried before Neurontin could be prescribed) in 2006. Some other anticonvulsants were moved to non-preferred status at the same time. Michael Brodeur, the head of formulary development and clinical pharmacy policies at Aetna, had communications with Pfizer and Warner-Lambert, but did not remember any specific communications about Neurontin. Aetna conceded that defendants, in any communications to Aetna about Neurontin, had not made any direct misrepresentations to it, its P & T Committee, or its formulary development team. Before January 2004, Aetna did not manage the drug class which included Neurontin. But Brodeur stated that, had the facts concerning the manufacturers' misleading marketing campaign surfaced earlier, he believed this would have led Aetna to start to manage this drug class at an earlier date. E. Statistical Evidence of Causation The summary judgment record included the statistical evidence presented by experts Dr. Meredith Rosenthal, Ph.D., and Dr. Raymond Hartman, Ph.D., that we described in Kaiser, slip op. at 13-16, 19-20. For the reasons stated in Kaiser, that evidence could be found by a reasonable factfinder to show that Pfizer's marketing of Neurontin for off-label indications caused a sharp increase in the number of prescriptions that Aetna paid for or reimbursed. -10- Dr. Rosenthal, an associate professor of health economics and policy at the Harvard School of Public Health, submitted an expert report in which she used standard econometric methods to quantify the impact of defendants' promotional activities on the number of off-label prescriptions of Neurontin written. Dr. Rosenthal's data on promotional spending included defendants' expenditures on detailing and advertising in professional journals. Her database included prescriptions paid for by Aetna, as did Dr. Hartman's. Dr. Rosenthal's analysis demonstrated that defendants' marketing of Neurontin for the off-label indications of bipolar, neuropathic pain, nociceptive pain, migraine, and doses over 1800 mg per day caused 43 million off-label prescriptions of Neurontin between 1995 and 2004. This total included prescriptions for Neurontin for these uses paid for by Aetna. She concluded that nationally during this period, defendants' off-label marketing caused 99.4% of the Neurontin prescriptions written by psychiatrists for bipolar; 27.9% of the Neurontin prescriptions written by neurologists for migraine; 70.0% of the Neurontin prescriptions for neuropathic pain; 84.7% of the Neurontin prescriptions for nociceptive pain; and 37.5% of the Neurontin prescriptions for doses exceeding 1800 mg per day. -11-