Cox-2 inhibitors. (Health Care Technology).

Increasing pharmacy costs are among the fastest growing segments of the health care budget. In fact, the total amount for drugs spent in the United States increased 27 percent between 1995 and 1997, related both to higher utilization and the increasing unit cost of new drugs. These attention-grabbing figures have focused health plan efforts on appropriately managing pharmaceutical costs, both from a long-term global perspective and a short-term approach emphasizing newly marketed products.

Over the next six months, inhibitor are expected to be approved by the FDA. This new class of drugs, investigated as a safer alternative to non-steroidal anti-inflammatory drugs (NSAIDs), is among the most highly anticipated medications to hit the marketplace. How health plans react to the launch of cox-2 inhibitors may serve as an example for future pharmacy management efforts.

As an alternative to NSAIDs, the potential market for cox-2 inhibitors is enormous. NSAIDs are among the most frequently used over-the-counter drugs and one of the most commonly prescribed drug classes in this country; more than 70 million prescriptions for NSAIDs were filled in the United States in 1991. (1) Enthusiasm for cox-2 inhibitors has even surfaced in the lay press, with such titles as: "Super Aspirin" in The New Yorker, (2) "Building a Better Aspirin" in Science, (3) and "A Revolution in Pain Relief?" in Business Week. (4)

Creating a proactive drug policy

In the face of pent up demand, coupled with presumably an aggressive physician and a direct-to-consumer marketing campaign by the manufacturer, what can health plans do to prepare for cox-2 inhibitors? Certainly, the frenzied experience associated with the launch of Viagra has illustrated the importance of having a rational policy in place at the time a drug becomes widely available. The unanticipated market demand for Viagra sent policymakers scrambling to determine the appropriate patient selection criteria, as well as frequency of use. For cox-2 inhibitors, it is already known that the market demand will be strong, but that the appropriate patient selection criteria will probably be an issue.

1. Review clinical information

Given the interest in creating a proactive drug policy, it is instructive to review what clinical information is available to policymakers prior to FDA approval. The bottom line is not much. While results of the preliminary phase II trials have been published, the key piece of clinical information is the results of the phase III clinical trials, conducted as part of the FDA approval process. While phase II trials have compared the drug to placebos, the phase III trials focus on the safety and effectiveness of cox-2 inhibitors compared to NSAIDs. Typically, the final results of phase III trials are not published until after FDA approval-after the drug is marketed.

For cox-2 inhibitors, the results of these trials will determine how they will compete with other NSAIDs. Do cox-2 inhibitors offer the same level of analgesia and anti-inflammatory action as NSAIDs? Do they have a reduced incidence of gastrointestinal bleeding compared to NSAIDs? If, as anticipated, the answer to both of these questions is yes, then cox-2 inhibitors could be considered a safer alternative. Therefore, prescription NSAIDs may be exchanged for cox-2 inhibitors. Additionally, the millions of patients taking over-the-counter NSAIDs could end up with a prescription cox-2 inhibitor.

2. Evaluate the cost of the new drug

The other critical piece of information needed by policymakers is the cost of the new drug. This, too, is unknown until the drug is marketed. Even a ballpark figure would be helpful, but typically only anecdotal "on the street" estimates are available. For example, if the cox-2 inhibitors are only marginally more expensive than current prescription NSAIDs, then the cost impact of converting to cox-2 inhibitors would be relatively minimal. Health plans could thus focus on the more significant cost impact of converting over-the-counter NSAIDs to prescription cox-2 inhibitors, and offer them as a covered pharmacy benefit, instead of an out-of-pocket expense. If the cost differential is high, health plans may be concerned about the impact of all uses of the new drug.

3. Identify appropriate patient selection criteria

The next step in this sequence of unknowns is the appropriate patient selection criteria. Is the safety profile so compelling that cox-2 inhibitors will be considered appropriate in all patients, or would they be most appropriately used in patients considered at high risk for NSAID-related complications? The risk of gastrointestinal complications is known to be higher in older patients, those with a history of ulcer disease, those taking high doses of NSAIDs for a prolonged period of time, or those taking steroids or anticoagulants. Reducing or eliminating these risks could save lives, prevent hospitalization, and incidentally save millions in health care dollars.

Would a reasonable approach be to target the use of cox-2 inhibitors at these high-risk patients? The answer to this question depends on the complicated interaction among the experience and desires of the prescribing physician, the patient who may specifically seek out a prescription for cox-2 inhibitors as a result of direct-to-consumer marketing, and, of course, a health plan's pharmacy policy.

Management strategies

A proactive policy regarding the use of cox-2 inhibitors may be challenging. The available management strategies typically include precertification, a tiered co-payment system, restricting prescriptions to a provider specialty, retrospective physician profiling, and physician education.

Precertification

With 70 to 80 million NSAIDs prescriptions written annually, and with cox-2 inhibitors potentially an alternative to a large majority, precertification is potentially an administrative nightmare, unless specific clinical criteria could be developed that would exempt many of the prescriptions from precertification. For example, patients at high risk of NSAID complications could be exempted from precertification. Many of these risk factors could be identified on a prescription or from the pharmacy database, such as the patient's age and other prescription drugs.

Tiered co-pay

A tiered co-pay system is an increasingly popular alternative to a closed formulary, giving patients access to all drugs, with some being assessed at a higher co-pay. The tiered system typically includes a group of therapeutically equivalent drugs divided into generic/formulary, brand/formulary, and non/formulary. Because of its safety profile, cox-2 inhibitors may be considered a class of their own and, thus, may not be suited to a traditional tiered co-pay system. However, a tiered co-pay system based on risk factors could he a novel approach. Those patients considered at highest risk for gastrointestinal complications could be assessed the lowest co-pay.

Restricting prescriptions to a provider specialty

Restricting prescriptions to a specific provider specialty is another management option, and one that was considered for Viagra, when prescriptions were limited to urologists. It is anticipated that the labeled indications for cox-2 inhibitors will include the treatment of osteoarthritis and rheumatoid arthritis. Therefore, restricting cox-2 inhibitor prescriptions to those written by a rheumatologist is a possibility. However, osteoarthritis is commonly managed by primary care physicians, and so this strategy may not be useful.

Retrospective physician profiling

Retrospective physician profiling is a powerful tool to influence physician behavior. However, profiling requires establishing a benchmark for appropriate cox-2 inhibitor use. Benchmarks may be based on the prescribing pattern of physician peers or on published guidelines. The prescribing patterns of physician peers may not be appropriate for a new, potentially patient driven drug. In addition, there are currently no published guidelines for the use of cox-2 inhibitors and it is unknown whether the provider community will advocate across the board substitution of cox-2 inhibitors for NSAIDs, or will advocate a more restricted use to high risk patients.

Physician education

Physician education may be considered. However, as already noted, there is relatively little clinical information published and the most appropriate use of cox-2 inhibitors may only emerge after their widespread use. Ultimately, the most powerful educational message may be a universal one, one that is consistent with an overall global strategy for managing drug costs and one that recognizes a cooperative partnership between health plan and provider. The simple message is that all new drugs should be used judiciously in the patients most likely to benefit.

Note

The Blue Cross and Blue Shield Association is an association of independent, locally operated Blue Cross and Blue Shield Plans. The information presented in this column does not necessarily represent the policy or views of either the Association or any of the Plans.

References

(1.) Anti-arthritic modication usage: 1991. Star Bull 1992;73:25-34.

(2.) Super Aspirin, The New Yorker, June 15, 1998. 32-35.

(3.) Building a Better Aspirin, Science, 1998;280:1191-1992.

(4.) A Revolution in Pain Relief? Business Week, February 16, 1998.

Elizabeth Brown, MD, is National Medical Consultant for the Blue Cross and Blue Shield Association in Chicago, Illinois. She can be reached by calling 312/297-6186 or via email at [e-mail].