Making comparative effectiveness work in cancer care

August 10, 2010

Patient preference needs to be weighed against overall societal benefits.

ABSTRACT: Patient preference needs to be weighed against overall societal benefits.

When pundits and politicos want to talk up the current healthcare reform plan in the U.S., they drop the term comparative effectiveness somewhere in the conversation. Given that more than $1.1 billion of the 2009 federal economic stimulus bill was allocated for comparative effectiveness research, it is one of the key elements driving the reform movement.

Comparative effectiveness is being used in cancer care in particular, as payers weigh the cost of treatment against its value to the patient. Two recent studies looked at comparative effectiveness in breast and ovarian cancer as well as in prostate cancer.

Prevention interventions

Victor Grann, MD, MPH, and colleagues at New York's Columbia University compared various prevention interventions in women at increased risk of ovarian or breast cancer. Dr. Grann's group used a Markov model with 25,000 Monte Carlo simulations to conduct a comparative effectiveness analysis of a simulated cohort of women with BRCA1/2 mutations. All women in the cohort were aged 30 to 65, had tested positive for a BRCA mutation, and had no cancer at baseline.

Using cost in dollars per life year saved and per quality-adjusted life year (QALY) saved, the investigators compared mammography with and without MRI, prophylactic oophorectomy or mastectomy or both, and chemoprevention with tamoxifen. Costs were based on the literature and expressed in 2009 dollars, and survival was based on SEER data and published studies of surgical, chemoprevention, and imaging interventions (ASCO 2010 abstract 6011).

The study found that prophylactic surgery was the most cost-effective intervention for women at increased risk of ovarian cancer (BRCA1 carriers) and breast cancer (BRCA1 and BRCA2 carriers). Of the preventive surgical options, prophylactic oophorectomy was the most cost-effective strategy for BRCA1 carriers: $1,741/QALY saved. For BRCA2, oophorectomy was $4,587 compared to both prophylactic oophorectomy and mastectomy procedures.

However, patients preferred screening modalities to surgical intervention. In breast cancer, MRI screening was associated with the longest quality-adjusted survival. For patients with the BRCA1 mutation, MRI and mammography provided 18.66 QALYs at a cost of $192,418 (at a discount rate of 3%). For patients with a BRCA2 mutation, MRI and mammography provided 19.12 QALYs at a cost of $177,934.


Based on their model, the investigators estimated that if the cost of MRI could be reduced by more than 50%, the use of MRI would be the most cost-effective of the studied interventions.

Emphasizing the importance of prevention to reverse the effects of having a mutation, Dr. Grann said that choosing an intervention requires that patients be informed of the harms and benefits of each strategy. "They should also appreciate the value of clinical trials to determine which prevention is better," he said.

"It is very important to do randomized trials of high-risk women who have mutations to determine whether the simulations we performed in our models offer the same real-world benefits," added Dr. Grann, who is a clinical professor of medicine and public health at the Herbert Irving Comprehensive Cancer Center and Joseph L. Mailman School of Public Health at Columbia.

Managing prostate cancer in older patients

In the second study, Julia H. Hayes, MD, and colleagues at Boston's Dana-Farber Cancer Institute used a cost-effectiveness analysis to compare therapeutic strategies for managing older men with early-stage, low-risk prostate cancer. A Markov Monte Carlo model was used to compare costs, QALYs, and incremental cost-effectiveness ratios (ICER) among 65-year-old men treated with radical prostatectomy, intensity-modulated radiation therapy (IMRT), brachytherapy, proton-beam therapy, and active surveillance.

The study found that active surveillance was most effective and provided an additional 9.1 months of quality-adjusted life expectancy (QALE) at an ICER of $2,074/QALY compared to radical prostatectomy (see Table 1).

TABLE 1 Cost-effectiveness of prostate cancer management strategies

Therapeutic strategyQALYsCost
Active surveillance8.58$30,422 ($3,546 per QALY)
Brachytherapy8.11$25,606 ($3,157 per QALY)
IMRT8.09$37,808 ($4,673 per QALY)
Proton-beam therapy7.96$53,828 ($6,762 per QALY)
Radical prostatectomy7.82$28,348 ($3,625 per QALY)

Among therapies used as initial treatment, brachytherapy was the least expensive and most effective, and provided an additional 3.5 months of QALE at a cost savings of $2,743. Although IMRT was similar to brachytherapy in QALE benefit, IMRT was more expensive ($21,050 vs $10,174).

In addition, when looking at selected outcomes--treatment-related complications, long-term side effects such as erectile dysfunction and urinary incontinence--the study found that active surveillance followed by brachytherapy as initial therapy was more effective and less expensive than IMRT, radical prostatectomy, or active surveillance followed by IMRT if there was no difference in treatment outcomes.

While active surveillance was associated with better quality of life, patient preference must be taken into consideration, said Dr. Hayes, an instructor at the Lank Center for Genitourinary Oncology.

"Active surveillance improves quality of life only if men on active surveillance are comfortable with this approach," she said. "It is my hope that this research will provide patients and practitioners with information that can be incorporated into the discussion of treatment options."


ELENA B. ELKIN, PHD Studies leave open question of strategies' value to patients

Both of theses studies represent timely and useful application of comparative effectiveness analysis with a particular emphasis on cost-effectiveness, said Dr. Elkin, who is from the Health Outcomes Research Group in the epidemiology and biostatistics department at New York's Memorial Sloan-Kettering Cancer Center. "The goal of cost-effectiveness analysis is to inform resource allocation decisions by providing information on the value of the money we spend on healthcare," she said.

The study by Dr. Grann is a reminder that healthcare decisions have cost consequences and that cost-effectiveness analysis can inform decisions, Dr. Elkin said.

"Prophylactic surgery offered better value for money than chemoprevention or screening," she said. "The study also found that screening with MRI was the most effective strategy because it was associated with the longest quality-adjusted survival, but it was also very expensive."

Dr. Elkin cautioned that identifying and implementing the intervention with the lowest cost-effectiveness ratio should not always be the goal. "Rather, we should aim to adopt strategies that provide the greatest health benefits within a societal threshold of our willingness to pay for health gains," she said. "In the U.S., there is no official threshold, and many decisions are made in the absence of information about value for money of the interventions patients receive."

Dr. Elkin praised Dr. Hayes' study for highlighting and simultaneously comparing the numerous treatment options available to older men with early-stage, low-risk prostate cancer and reflecting the real clinical decisions patients face. She also noted that prior research showed that men's preferences for the potential outcomes of different management strategies vary widely.

"We should be cautious about assuming that average preferences for these outcomes are applicable to each individual patient," she said. "In this case, further analysis may help us identify subgroups of men for whom radiation or surgery provides better value for money than active surveillance because these men are less bothered by the potential side effects of treatment."