Medical Test Validity Will Be Debated In 2016: 5 Storylines To Watch


Despite lots of headlines, an underappreciated storyline this year was the undercurrent surrounding the validity of medical tests:

—The Milwaukee Journal Sentinel published a long Watchdog Report focused primarily on quality issues with waived lab tests, which don’t require FDA approval.

—The headline of a shorter version in the Wall Street Journal asked whether lab testing is the Wild West.

—The Journal was responsible for tugging at a similar thread over the last few months and has unraveled many of the claims of the most well-known technical innovator in lab testing, Theranos.

—One of the other Theranos objectives has been support of consumer-driven lab tests, starting with legislation in Arizona. The billionaire investor Mark Cuban started a vigorous online debate when he suggested people have blood tests done quarterly to monitor their own health. The response to Cuban from many physicians was swift, with the majority seeming to point out the perils of false positives and false negatives, and the potential for overdiagnosis and overtreatment.

The Atlantic asked about the clinical validity of genetics tests being used to make medical decisions, which makes the push for consumer genomics described in this “Signal” podcast all the more interesting.

Why do these stories matter for drug development? Particularly in oncology, similar tests are increasingly used to select patients for clinical trials of drugs as well as guide therapy for approved drugs. Although drug pricing dominated the storylines, lab test headlines are a symptom of the larger issue: selecting the proper patients is critical for the industry to demonstrate that a drug improves patient outcomes, which is the gold standard in the value and pricing argument. The analytical and clinical validity of medical tests could be viewed as the lynchpins to demonstrate value for a drug.

Excluding ongoing discoveries about the complexity of cancer biology, here are five medical testing stories to watch in 2016:

1. The FDA will push harder on more regulation. In late 2015, the agency published a report on 20 case studies showing potential dangers of lab-derived tests and a companion blog post on their goal to have more oversight. (A handful of the case studies were to guide cancer treatment decisions.)

2. To “improve the quality and accuracy of genomic tests”, in late 2015 the FDA launched the precision FDA initiative, an online portal for researchers to exchange information. As part of the platform, the FDA appears to be engaging the genomics community in work that will result in setting standards for these assays.

3. Immuno-oncology is one of the most competitive areas of drug development. For the PD-1 and PD-L1 checkpoint inhibitors alone, there are multiple drugs in clinical trials as well as two anti-PD1 antibodies, nivolumab and pembrolizumab, already approved by the FDA. Only one drug and indication, pembrolizumab in non-small cell lung cancer, has an associated companion diagnostic, meaning the test is written into the label of the drug. However, there are at least four assays to measure PD-L1 in varying stages of development. In 2015, the FDA, American Association for Cancer Research, and American Society of Clinical Oncology brought stakeholders together in a workshop that resulted in agreement to develop an information package to allow comparison of the analytic performance of the different assays. While we’ve seen this type of collaboration before*, the difference I see here is the fast timing relative to drug approval and the highly competitive nature of the checkpoint inhibitors.

4. Liquid biopsies are coming on strong. On top of analytical considerations, comparisons to the data for traditional biopsies will add to questions of what test provides the best actionable result.

5. Finally, the question we’ve all been waiting for an answer to: does selecting therapy for patients based on mutations in their tumor lead to improved outcomes? The answer is clearly “yes” in some cases, like when the mutation is HER2 in breast cancer or more recently for BRAF v600 in melanoma. The answer is “sometimes” when changing histologies. Giving vemurafenib, which targets BRAF V600, to patients with non-melanoma cancers did lead to responses, but only in a subset of patients. These studies are used by payers to make decisions about coverage for genomic screening panels. The only related randomized control trial that has been completed, the SHIVA trial in France, also found that targeted agents didn’t improve survival when used outside their approved indication. While disheartening, small trials such as this Phase I trial at the MD Anderson Cancer Center suggest that there can be improvement. We still have work ahead to demonstrate improved outcomes based on genomic screening and targeted therapy.

Proper treatment selection is necessary for scientifically driven drug development and that requires assays able to reliably distinguish between patients. An issue repeatedly heard from test providers is that when reimbursement is too low—or lacking entirely—it discourages investment. Payers want to see improved patient outcomes. As drug developers, we need to be an active part of these discussions if we want to meet the ultimate goal of delivering drugs with greater value for patients.

*Prior examples of multi-stakeholder efforts directed to oncology testing include:

—The American Society of Clinical Oncology and the College of American Pathologists (CAP) providing guidance for HER2 testing for trastuzumab, which now has 10 approved companion diagnostic assays.

—CAP, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology providing guidelines for testing for epidermal growth factor receptor and anaplastic lymphoma kinase for use of tyrosine kinase inhibitors in lung cancer.

[Editor’s note: To tap the wisdom of our distinguished group of Xconomists, we asked a few of them to answer this question heading into 2016: “What is the most pressing issue for the innovation community in 2016?” You can see more questions and answers here.]

Laura E. Strong, Ph.D. has more than 15 years of operational, strategic, and clinical development experience in biotech and health technology. Most recently, Dr. Strong is the founder and CEO of Propagate Health, which builds problem-oriented innovation networks across healthcare, life sciences, and technology stakeholders. Follow @scientre

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