In the News

Mar 23, 2009

The real cost of treating off-label and off-guidelines

Med Ad News

By Ed Kissel

In the specialty of oncology, physicians take some latitude in treatment choices given the widely held belief that each patient’s situation is unique, and that the best chance for survival or improved quality of life requires a customized approach. In contrast, the payers responsible for reimbursement of physicians’ choices often question whether deviating from standard treatment is justified, especially when the treatment includes the use of expensive drugs. Caught in the middle of these often opposing forces is the pharmaceutical oncology marketer, whose job it is to effectively sway physician opinions and behavior.

The debate between "off-label" and "off-guidelines" is multifaceted. If cancer patients are treated off-label, many believe that efficacy and safety might be compromised or costs will increase exponentially.

However, this argument is inherently false in oncology because physicians practice ethical medicine when treating cancer patients. Additionally, most "off-label" use is extensively supported by published, peer-reviewed literature that demonstrates a significant clinical benefit to patients.

The effective application of pharmaceutical marketing that drives the clinical development of a product and the importance of clinically relevant (not just statistically significant) data is what really influences physician decisions. These early, positive clinical results are what gains early acceptance of a particular drug and the most favorable influence toward FDA approval.

Being the first to meet a significant medical need is imperative. For example, in the colorectal cancer market, Erbitux quickly became the market leader in the difficult-to-treat relapsed patient population where, previously, there was no effective treatment. Vectibix was launched a couple of years thereafter, but was unable to sustain its market position because the drug was not able to show clinical significance to convince physicians to replace Erbitux.

Despite long-held suspicions between doctors, payers, and pharmaceutical companies, the startling truth is that only 10% to 20% of metastatic cancer patients receive off-guideline treatment. Using a broad interpretation of NCCN guidelines in non-small cell lung cancer, about 97% of metastatic first-line patients are treated to guidelines and about 60% of metastatic second-line-plus patients are treated to guidelines. Treating to published guidelines does not necessarily mean cost savings, as some recommendations are more costly than what is actually being used by physicians.

The largest portion of the expense comes from aggressively treating third-line-plus patients, where guidelines call for best supportive care or treating poor performance status patients.

As the entire healthcare system comes under greater scrutiny, caregivers can expect new incentives that encourage oncologists to adhere to strict guidelines – even though these initiatives will not significantly cut healthcare expenditure.

Our research explored the potential financial impact to limiting doctors’ ability to treat these patients based on clinically accepted treatment guidelines and found that it would only save around 10% of the total drug cost. The most effective way to quickly reduce costs in oncology would be to limit options based on poor performance status patients as many treatment guidelines suggest; however, these patients currently make up less than 5% of the overall market and drugs are typically given for much needed symptomatic improvement.

For the pharmaceutical oncology marketer, this means that some risk of cost cutting is inevitable unless their efforts to influence physician behavior were guided by sound clinical data suitable for guideline consideration.

The greatest challenge – and greatest return on market research – is in accurately segmenting markets to understand the clinical benefit of a drug in a tumor setting. The latest treatment guidelines developed are dividing larger tumor markets into smaller niche patient cohorts, and it is expected that this pattern will only intensify.

To put the market opportunity into the proper context, marketers must more accurately size the market and understand the unmet medical need to drive clinical investment and tie into proper reimbursement.

Editor’s note: This is one of an occasional series of guest columns. Ed Kissel is VP of quantitative analysis for Intrinsiq (, a source for U.S. oncology data and analysis.