Call for greater use of comparative effectiveness studies to help advance disease management

"In osteoporosis, it is unlikely that prospective, head-to-head clinical fracture trials will be conducted due to the large number of patients required to show a difference between two effective therapies," said Professor Delmas, REAL study author, Université Claude Bernard, Lyon. "Large, comparative, retrospective analyses, like the REAL study, are one way to fill the knowledge gap and should be considered in the total body of evidence for a drug to optimise treatment decisions and enhance patient care."

NOTES TO EDITORS:

About the REAL study

The RisedronatE, ALendronate (REAL) cohort study was a retrospective analysis of a health service utilization database. These databases are generated by medical insurers for the payment or reimbursement of health services. They include longitudinal, patient specific information such as diagnosis codes for reimbursable expenses (e.g. fractures) and pharmacy dispensations. The REAL study utilized a U.S database of 12 million insured participants. It was a pooled dataset of one health plan within Ingenix Lab/Rx, and the 100 employer health plans within Medstat Marketscan.

From the dataset, women aged 65 years and older were identified who were new users of weekly bisphosphonate therapy, either risedronate 35 mg (N=12,215) or alendronate 35 mg or 70 mg (N=21,615). Patients had to have at least six months medical history prior to treatment initiation and were followed for 12 months after bisphosphonate initiation to assess 6 and 12 month fracture incidence at both the hip and at a composite group of non-vertebral sites (hip, wrist, clavicle, humerus, pelvis and leg). Standard statistical methods were used to compare the incidence of fracture between the risedronate and alendronate groups (Cox proportional hazard modeling). As with all retrospective cohort studies, an important concern is that in real world clinical practice patients are not randomly assigned to treatment groups, potentially introducing "selection bias" into the results. The risedronate and alendronate groups were compared for risk factors for fracture at baseline, and all results were risk-adjusted for potential differences in baseline fracture risk.

In the study, patients on risedronate had 46% (p=0.02) and 43% (p=0.01) lower incidence of hip fracture than patients taking alendronate at 6 and 12 months, respectively. Prior to risk adjustment for baseline differences in fracture risk, the crude incidence of fracture in each population was as follows: At six months, 0.29% of alendronate patients had sustained a hip fracture, compared to 0.17% of risedronate patients. At 12 months, 0.58% of alendronate patients had suffered a hip fracture, compared to 0.37% of risedronate patients.