Capping Drug Benefits—Will it Help Control Healthcare Costs?

Pharmacology Watch

Controlling healthcare costs is tricky business, and sometimes the best intentions have adverse outcomes, as pointed out in a new study in the June 1 New England Journal of Medicine. Financial caps on Medicare drug benefits were reviewed in a large group of Medicare + Choice beneficiaries in northern California (over 150,000 individuals) who had $1,000 annual drug benefit cap compared to those who did not have a limit on their drug benefits (41,904 individuals). The cap on pharmacy costs was effective at reducing pharmacy costs by 31% (95% CI, 29 to 33%), but the capped group had total healthcare costs that were only 1% lower overall (95% CI, -4 to 6%). Those with capped benefit were more likely to visit the emergency department (RR, 1.09 [1.04 to 1.14) and were also more likely to be hospitalized for non-elective admissions (RR, 1.13 [1.05 to 1.21]). The death rate was also higher in the capped group (RR, 1.22), with a difference of 0.68 per hundred person-years [0 .30 to 1.07]. Patients on chronic medications for hypertension, hyperlipidemia, or diabetes were more likely to be nonadherent to drug therapy if they had a capped benefit and, for each of those diagnoses, physiologic outcomes were worse for subjects with capped drug benefits, including systolic blood pressure over 140 mm Hg, serum LDL greater than 130, and a HbgA1c over 8 (respective risk ratios 1.05 [1.00 to 1.09], 1.13 [1.03 to 1.25], 1.23 [1.03 to 1.46]).

The authors conclude that a cap on drug benefits was associated with lower drug consumption and unfavorable clinical outcomes. In patients with chronic diseases, the benefit cap was associated with nonadherence to drug therapy and poorer clinical outcomes. Overall, any savings realized by a drug cap was offset by an increase in the rate of hospital admissions and emergency department visits (N Engl J Med. 2006;354:2349-2359). An accompanying editorial states, "Effective strategies for reducing the level and growth of spending will need to rely on tools other than high-deductible plans and limits on benefits" such as preventative care and dealing with the obesity epidemic, as well as improved information systems (N Engl J Med. 2006;354:2385-2386).

The STAR Trial (Tamoxifen and Raloxifene)

Results from the long awaited STAR trial (the National Surgical Adjuvant Breast and Bowel project Study of Tamoxifen and Raloxifene) have been published as an early release article on the JAMA website. This multicenter trial of nearly 20,000 women mean age 58.5 years with an increased 5-year breast cancer risk was designed to compare the incidence of invasive breast cancer, uterine cancer, noninvasive breast cancer, bone fractures, and thromboembolic events in those treated with oral tamoxifen 20 mg per day or raloxifene 60 mg per day over 5 years. Tamoxifen has been used to treat early and advanced breast cancer for more than 30 years, and has also been shown to reduce the risk of invasive and non-invasive breast cancer in women who were at increase risk.

The STAR was designed to see if the second-generation selective estrogen receptor modulator (SERM) raloxifene would also be effective in this role. Raloxifene is currently approved for the prevention and treatment of postmenopausal osteoporosis. After 5 years, there were 163 cases of invasive breast cancer in the tamoxifen group and 168 in the raloxifene group (incidence, 4.30/1000 vs 4.41/1000; RR, 1.02; 95% CI, 0.82 to 1.28). Noninvasive breast cancers were slightly more common in the raloxifene group (1.52 vs 2.11 cases per 1000; RR, 1.40; 95% CI, 0.98 to 2.00). The rate of uterine cancer was lower in the raloxifene group (RR, 0.62; 95% CI, 0.35 to 1.08). No differences were found for other invasive cancers, ischemic heart disease, stroke, or osteoporotic fractures. Thromboembolic events were more common in the tamoxifen group (RR, 0.70 nickel and 95% CI, 0.54 to 0.91). Cataracts and cataract surgery were also less common in the raloxifene group. The overall death rate and the causes of death were the same in both groups.

The authors conclude that raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer, and has a lower risk of thromboembolic events and cataracts but is associated with a nonsignificant higher risk of noninvasive breast cancer (JAMA early release, posted online June 5, 2006 This study is important because although there was no control group, tamoxifen is proven to reduce breast cancer incidence and is approved for this indication, but with a higher incidence of endometrial cancer, thromboembolic events, DVT, and stroke. Previous studies have shown that raloxifene reduces the risk of estrogen receptor-positive invasive breast cancer by up to 66% over 8 years of treatment compared to placebo (MORE and CORE trials [JNCI 2004;96:1751-1761]). Quality-of-life issues have been a concern with SERMs, and was hoped that raloxifene would be the better tolerated than tamoxifen.

An accompanying article also published online focused on patient reported symptoms and quality of life issues in participants in the STAR trial. There was no significant differences between tamoxifen and raloxifene in patient reported outcomes for physical health, mental health, and depression, although the tamoxifen group reported better sexual function (age-adjusted repeated measure odds ratio 1.22%; 95% CI, 1.01 to 1.46). Women in the raloxifene group reported more musculoskeletal problems (P = .002), dyspareunia (P < .001), and weight gain (P < .001). Women in the tamoxifen group reported greater severity of gynecological problems (P < .001), vasomotor symptoms (P < .001), leg cramps (P < .001), and bladder control symptoms (P < .001). Overall, mean symptom severity was low among women in both groups (JAMA. early release, posted online June 5, 2006

An accompanying editorial points out that tamoxifen is rarely used as an agent for protection against breast cancer in women at risk, and it had been hoped that raloxifene would provide an alternative with equal efficacy for breast cancer and less adverse effects. Unfortunately, the STAR trial does not clearly demonstrate this. Both drugs are effective at preventing breast cancer but both carry increased risk of endometrial cancer and thromboembolic events. Raloxifene has an advantage of being approved for reduction of osteoporotic fractures, but whether this will convince primary care physicians to prescribe the drug for women at risk of breast cancer is unknown (JAMA. early release, posted online June 5, 2006

FDA Actions

Merck has received approval to market a vaccine to prevent human papilloma virus (HPV) infections. The vaccine received a priority review, and is seen as a major advance because of the association between HPV and cervical cancer. The vaccine targets HPV types 16 and 18, which are responsible for 70% of cervical cancers and types 6 and 11, which are the most common cause of genital warts. HPV vaccine is given in 3 separate IM injections over 6 months and will cost $120 per dose, $360 for the entire course. It is approved for use in females age 9 to 26. Merck will market the HPV vaccine as Gardisil.

Merck has also received approval to market its live zoster vaccine for the prevention of herpes zoster in individuals aged 60 and older. The vaccine, which is a live attenuated varicella-zoster virus, is given as a single-dose subcutaneous injection. The vaccine has been shown to significantly decrease the rate of varicella-zoster (shingles) in older adults and decrease the rate of postherpetic neuralgia in those who developed shingles despite the vaccine. Merck will market the live zoster vaccine as Zostavax.

This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: