The RegenceRX Methodology

RegenceRX ranks evidence of efficacy based on levels of confidence in clinical data. The committee gives a “high confidence” ranking if the data precisely estimates extent of benefit and chances of success in meeting goals. It categorizes as "uncertain confidence" situations in which it is not certain of efficacy due to unreliable clinical data. Drugs fall into a ‘lack of confidence’ group if their efficacy is unknown, and the extent of benefits and chances of success are undetermined, and bias and confounders likely interfered with trial results. The term confidence replaces what Regence used to call ‘reliable’ and the criteria it uses to assess reliability is based on work done over the past decade in conjunction with criteria set by The Consort Group based on evidence-based medicine. Among factors contributing to reliability of trial design are blinding, the validity of clinical endpoints, and drop-out rates.

The actual decision process, however, is slightly more complicated, as factors beyond confidence level come into play. Decisions for 2011 group new drugs into four categories: high confidence in evidence for efficacy/many other treatment options; high confidence in evidence of efficacy, with no other options; "not high confidence" in efficacy/many other options; and "not high confidence" in evidence for efficacy/ with no other options.

Although some of its clients assign quantitative values to drugs based on RegenceRx reviews, the HTA itself does not; nor does it put a percentage to the weight of each input it uses to make decisions, said Sean Karbowicz, a manager of Clinical Pharmacy Services at RegenceRx, who spoke about the pharmacy benefits management firm’s perspectives on 2011’s new drugs at the Academy of Managed Care Pharmacy in October.

Here’s one example of the decision-making process: Both Tasigna and Sprycel, made by Novartis AG and Bristol-Myers Squibb Co., respectively, are follow-on BCR-ABLE kinase inhibitors. They are already FDA approved as second-line therapies for Philadelphia-positive CML patients resistant or intolerant to standard of care Gleevec (imatinib), also made by Novartis. In 2010, the manufacturers received FDA approvals of the drugs’ use in first-line therapy (Also see "Bristol's Once-daily Sprycel Faces Off Against Novartis' Tasigna After Clearance In First-line Leukemia" - Pink Sheet, 28 Oct, 2010.). The clinical trials showed both drugs were more effective than Gleevec in the first-line setting, with results based on complete cytogenic response rates, or surrogate endpoints (Tasigna’s CCyR was 78-80%; Sprycel’s was 77%, and Gleevec’s is 65-66%). Regence was concerned about the tightness of the correlation between the CCyR surrogate endpoint and overall survival, but oncologists confirmed the data was clinically meaningful.

Safety was also a key factor in the decision. The drugs have similar, but not identical, profiles. Both are saddled with a QT prolongation risk, but only Tasigna has a black box warning flagging the issue. “We couldn’t understand with certainty why one has a black warning box and one does not,” said Karbowicz. As a result, he noted, distinguishing which drug might be safer was hard. In addition, Sprycel has a new warning for risk of pulmonary arterial hypertension. Since Gleevec has a long history of efficacy and safety in the first-line setting, cost also became an issue in the valuation. Tasigna and Sprycel are “significantly more costly than Gleevec for first-line treatment [Monthly AWPs: $9,817 for Tasigna; $9,458 for Sprycel; and $6,354 to $12,707 for Gleevec, but lower dose at the lower price is most common].” Ultimately, Regence put both drugs on formulary, with a prior authorization that makes them available at the lowest brand co-pay.