Significant Hurdles Must Be Overcome to Actualize the Value of Personalized Medicine

June 2014, Vol 5, No 5

Los Angeles, CA—An agenda for personalized medicine must address quality control for test performance, billing and coding for molecular tests, and other practical challenges. The most important item in the agenda is the promotion of clinical utility to enhance value, said Michael A. Kolodziej, MD, National Medical Director, Oncology Solutions, Aetna, at the Fourth Annual Conference of the Association for Value-Based Cancer Care.

Although the final goal—an improvement in value—is universally recognized, there remains a shortage of ideas on how to achieve it, Dr Kolodziej said.

Personalized medicine depends on the ability to pay for diagnostic and therapeutic products. The cost of cancer care is increasing at double to triple the rate of other medical costs. New technologies may have an impact on bending this cost curve, but new technologies will invariably cost more than old technologies. Therefore, to favorably affect the value equation, quality will have to be improved, said Dr Kolodziej.

The 3 legs of the personalized medicine stool are mutation analysis, big data, and targeted therapy. Mutation analysis leads to a therapeutic decision in an effort to enhance outcome. Personalized medicine can add to the quality component of the value equation by improving survival and quality of life and reducing toxicities.

The 5 hurdles that must be cleared to fully realize the value of personalized medicine include:

  • The tests
  • The score-keeping
  • The evidence
  • The doctors
  • The treatments.

Molecular Tests’ Utility
The test must have clinical utility, which means that the information provided makes a contribution to and improves current optimal management of the patient’s disease. The best examples of mutations that predict response to therapy are HER2/neu in breast cancer and non–small-cell lung cancer (NSCLC), RAR-alpha in acute promyelocytic leukemia, and BCR-ABL in chronic myeloid leukemia.

“NSCLC is the poster child. We’re cataloging 9000 mutations (in NSCLC), and there are a handful that make a difference,” Dr Kolodziej said. “EML4-ALK of course is actionable [with crizotinib], and there’s good evidence of clinical utility.” Most other mutations have no associated targeted therapy that is approved by the US Food and Drug Administration.

The test must also have clinical validity, meaning that it relates to the clinical outcome of interest. “We must agree that we have a long way to go to establish clinical utility,” Dr Kolodziej said.

Analytical validity of molecular tests is problematic without proficiency testing and standards, and improved analytical validity of next-generation sequencing is needed, said Dr Kolodziej. Targeted next-generation sequencing panels miss a variable amount of content depending on the genes, and exome sequencing misses 5% to 10% of coding sequences. Most doctors do not think about analytical validity when ordering a test.

Coding and information technology challenges with respect to molecular tests also abound. “There are no codes for next-generation sequencing,” Dr Kolodziej noted. The conversion of stack Current Procedural Terminology codes to specific codes will improve the ability to track utilization, enable decision support tools, and enforce coverage policy.

The correct amount of testing to optimize patient outcome is unknown. The percentage of eligible patients who receive Oncotype testing is <70%. “How do we get doctors to do it right?” asked Dr Kolodziej. The use of value pathways and statistical probabilities of response according to mutation or combination of mutations are approaches that may represent the future, he said.

The Value Proposition Conundrum
Expense, including high copayment, is not the only hurdle to newer treatments, Dr Kolodziej said. Targeted agents have side effects that cause dose interruption or dose reduction within the first month of therapy in up to 33% of patients, and discontinuation in as many as 10%.

The marketing of genetic tests directly to consumers contributes to the demand for testing, whether evidence-based or not. Aetna documents that non–evidence-based requests for BRCA testing have increased by 10% annually since a direct-to-consumer campaign in 2004.

The ultimate question is the value proposition offered by personalized medicine. Will it improve the quality, safety, and cost-effectiveness of delivered healthcare, or will it drive additional medical costs with marginal healthcare?

All of these challenges occur in the setting of unsustainable growth in healthcare spending and the near uniform agreement that we need to spend our money in a more intelligent, impactful way. Currently, approximately 30% of health spending is waste, including unnecessary services, prevention failures, fraud, inflated prices, inefficient care delivery, and excess administrative costs, according to the Institute of Medicine.

Our values should guide the approach to creating a better healthcare system, with the goal being better patient outcomes, Dr Kolodziej said.

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