Balancing Innovation With Cost in Diagnostic Testing

Advances in the understanding of cancer biology have presented molecular targets that can prove valuable for prognosis. The use of molecular diagnostic testing has blossomed simultaneously over the past 15 years, and a major area of research has been the development of targeted therapies that can be used to individualize treatment based on molecular profiles. The research has yielded major clinical successes, including the first targeted therapy, imatinib, for patients with chronic myeloid leukemia, and similar efforts are ongoing for other cancers. At the recent 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, a search of abstracts and presentations yielded 842 results for the word target. These ranged from papers that studied molecular targets by disease type; by classification (ie, angiogenesis targets, growth factors); and newer immunologic therapeutics, including immune checkpoint-blocking antibodies that boost the patient’s immune system to attack the malignant cells (ie, anti-CTLA-4 and anti-PD-1 antibodies).

As clinical targets in more common malignancies including breast, lung, and colon cancers emerge, testing and treatment options will increase. Balancing these choices with the high costs associated with the new technology will be the challenge in order to determine value in oncology care.

The Rising Cost of Healthcare

As cancer research has made impressive progress toward treating and improving patient outcomes, costs have risen exponentially over the past 3 decades.¹ The cost of healthcare has become an important topic in the United States. During his keynote address at ASCO’s annual meeting, Michael Porter, PhD, MBA, a world-renowned expert in economics and competitiveness who has written extensively about healthcare, emphasized the importance of considering cost of care in cancer treatment. During his presentation, “Value-Based Health Care Delivery,” Porter implored the cancer community to begin seriously thinking about how to maximize the value of care.

These ideas are being considered in the community at large, as 361 presentations at the meeting included the word cost in the title. Porter’s presentation looked for ways to maximize value of care. As a first step, testing and treatment regimens (“pathways”) need to be evaluated to minimize cost while maintaining or improving quality of care for patients, he said. This is especially important when considering newer molecular testing and targeted therapies, which may be more expensive compared with older tests and treatments. In my practice, we have implemented significant measures to deal with some of these cost issues while maintaining quality care in line with clinical, evidence-based guidelines.²

In June 2015, ASCO released a framework for assessing the value of newer cancer therapies and treatments. The hope is to establish a tool that physicians and patients can use, to determine the benefits and costs of various treatments. It is hoped that this will be useful in establishing the value of newer, costlier treatments as compared with standard treatments.³

The Center for Medicare and Medicaid Innovation (CMMI) has also established a process by which oncology specialty physician practices can apply to participate in a new payment model, which allows the practice to be reimbursed in an innovative way—arrangements that include accountability for episodes of care surrounding chemotherapy administration for cancer patients. This new Oncology Care Model (OCM) aims to provide higher quality coordinated oncology care. A pioneer program established by CMMI for a medical subspecialty, OCM ascertains that the cost of oncology services is being reevaluated.⁴

These examples clearly indicate that “value” has developed into an important aspect of clinical decision making for physicians and patients alike.

A Provider’s Perspective on Diagnostic Testing

I am one of 5 practicing medical oncologists at Crystal Run Healthcare, a physician-owned, multispecialty practice of over 300 physicians at multiple sites in New York. Crystal Run Healthcare has been a leader in value-based care for the past 10 years, being one of the first 27 accountable care organizations (ACOs) in Medicare Shared Savings Program and one of the first 6 ACOs to be accredited as part of the National Committee for Quality Assurance. We have also recently established our own healthcare plan, which also mirrors our philosophy of being a value-based organization. The oncology division was among the first 16 community cancer care practices nationwide to be certified by ASCO through their Quality Oncology Practice Initiative. In the oncology division, we have worked on variation reduction programs and established that pathways in oncology patient management result in high-quality, cost-effective care.

We have implemented a similar value-based approach to molecular diagnostic testing and treatments in my community setting.

Molecular diagnostic testing provides new information that can broaden treatment options, but in some cases these tests are not needed. Historically, pathology reports included information that described histologic findings and immunohistochemical stain profile. As targets such as Her2/neu (breast), epidermal growth factor (EGFR) (lung), KRAS (colon), and BRAF (melanoma) emerged, these became part of the routine testing done for each type of cancer. Newer methods to identify these targets include next generation sequencing (NGS), which allows for sequencing of tumor tissue or patient serum for somatic and germline mutations in a very short period of time. The advances in the chemistry behind these techniques have allowed for rapid sequencing but also a significant decrease in cost per base tested. Some of these tests may not be very expensive (eg, fluorescence in situ hybridization or FISH testing) but may be performed on a large number of patients (eg, all breast cancer patients), which can lead to multiplicative increase in cost for a population. More expensive molecular diagnostic tests (eg, NGS) are typically prescribed for select patients. Historically, physicians have not considered cost in determining treatment.

Multiplicative Cost of Less Expensive Tests

To illustrate an example of the multiplicative cost of a relatively inexpensive test in a large population, we will look at 2 patients with invasive breast cancer. The expression of Her2/neu can be evaluated with immunohistochemistry (IHC) assays as well as with more expensive, but more precise, FISH techniques. Her2/neu testing in invasive breast cancer is an important prognostic and predictive factor. Trastuzumab in the adjuvant and metastatic setting, and several other drugs, including lapatinib and pertuzumab in the metastatic setting, are important therapeutic options available to patients based on positive Her2/neu testing. The National Comprehensive Cancer Network (NCCN) Guidelines indicate that FISH testing should be pursued specifically when IHC testing is equivocal at 2+. When IHC is negative, 1+ (negative), or 3+ (positive), then FISH can be deferred—IHC being more definitive. Since discordance between IHC and FISH testing is observed in less than 2% of patients, appropriate use of FISH can avoid the excess cost.⁵

Case Studies

At our community hospital Tumor Board, we discussed a 43-year-old woman who had a 2.5-cm invasive breast cancer that was estrogen receptor- and progesterone receptor-positive, and whose IHC was 3+ for Her2-neu. FISH testing, performed as part of the hospital’s routine protocol, was also positive. At the same tumor board, a 69-year-old woman had a 0.8-cm invasive estrogen receptor— and progesterone receptor–positive breast cancer, with Her2-neu 1+ by IHC (negative). FISH testing, performed as part of our routine protocol, was negative as well.⁶

The cost of IHC is approximately $125 per specimen, and the cost of FISH is approximately $450 per specimen. Given that 300 breast cancer cases are treated at our regional medical center, at least $100,000 in extraneous FISH tests could be avoided. Performance of FISH testing on every specimen is redundant, wasteful, and a clear deviation from national standards. Oncology has always been, and has increasingly become, a multidisciplinary field. Pathologists, surgeons, radiologists, and medical sub- specialists—including pulmonologists, gastroenterologists, and others—are all an important part of the team of physicians needed for the optimal treatment of cancer patients. One of my roles during Cancer Committee meetings and Tumor Boards at our local hospitals has been educating others involved in the care of oncology patients to incorporate value-based practices. At a recent meeting, following initial resistance to the change in practice on IHC and FISH testing in breast cancer patients, I discussed the NCCN and ASCO guidelines, and we approved a programmatic change to reflect adherence to national guidelines. In addition, as we at Crystal Run Healthcare have expanded our clinical services, we have pursued internal reviews of breast biopsy and pathology services within the practice through the use of our own Ambulatory Care Center and our own pathologists, where we are assured of a value-based approach.

NGS is also an important tool that can be used to select patients for newer targeted therapies and to enrich the clinical trial patient cohorts to include best responders to newer agents. While the appropriate use of molecular testing is important, unnecessary testing can lead to a significant escalation of expenses since each NGS test can cost from $1500 to $5000, depending on the type of sequencing conducted.

Recently a 78-year-old man, an active smoker, with a new diagnosis of non—small cell lung cancer, was referred to me by a primary care physician (PCP) in the community. The patient had advanced disease, and the pathology report indicated that he had a poorly differentiated adenocarcinoma, with ALK-negative and EGFR-negative status. The patient’s PCP, at the request of the patient’s son, had asked the pathology department to send the NGS test. It was clear to me when I saw the patient that he was not a candidate for a clinical trial based on his performance status, nor would he be able to tolerate standard chemotherapy. Molecular testing in this patient was unnecessary. It is reasonable to limit NGS to those patients who are eligible for clinical trials where the information may be useful. It may also be helpful in patients with a good performance status who have already received standard therapies, and where the extended testing could help identify beneficial alternate treatment strategies. This type of testing should also be generally ordered by oncologists who have determined the clinical utility of the test.

Optimizing Clinical Pathways

In our practice, treatment protocols are currently chosen at the discretion of the treating physician. We are committed to treating patients using clinical pathways based on data we obtained from a pilot project in our practice last year. We created our own breast cancer clinical pathway based on NCCN guidelines and used standard ranking criteria to choose optimal pathways.

• Protocols were first selected based on the best clinical outcome.
• Among equivalent regimens, the next selection was based on least toxicity.
• Finally, among regimens that were considered most effective and least toxic, regimen selection was based on lowest cost.

Data around costs associated with PEG-filgrastim and PET scan use (a costly but important part of treatment and surveillance programs) were collected on patients treated between March 2012 and September 2012 (before implementation of pathway) and compared with patients treated between March 2013 and September 2013 (after implementation of pathway) (Table). The average cost per patient for PEG-filgrastim use dropped by $3331 per patient during the measured interval, for a total cost savings of $227,000. There was no associated increase in febrile neutropenia or hospitalization. The calculated cost savings for PET scan use were $143,000.

With increasing awareness of NCCN guidelines among our oncologists, the reduction in growth factor and PET scan utilization was also seen in other cancers that were not on pathways. This experience has led us to actively embrace the use of clinical pathways, which can heighten an oncologist’s awareness of cost and appropriate use of diagnostic testing. For example, in the patient discussed earlier, NGS would not have been ordered since he was not a candidate for active therapy.

Reconciling the rapid advances, the exciting world of new targeted therapies, and the need to pursue value-based care is integral to the future of oncology patient care. Balancing the appropriate use of diagnostic testing and treatment and ensuring that opportunities for improved survival and quality of life are not missed is the goal of value-based oncology. There certainly are difficult decisions that need to be made when defining, as a medical community, what makes a test or treatment “worth” the cost (either toxicity or monetary). With medical progress, the value-based aspect of using new drugs, testing, and techniques needs evaluation. Elimination of duplicative and unnecessary care by adherence to evidence-based clinical pathways can result in cost savings that can then be invested in the appropriate use of innovative tests or treatments. EBO

Gnanamba Varuni Kondagunta, MD, is a medical oncologist with Crystal Run Healthcare.References

1. Bach B. Cost and value in cancer treatment choice. Talk presented at: 2015 ASCO Annual Meeting; May 29—June 2, 2015; Chicago, IL. http://meetinglibrary.asco.org/content/112044?media=vm. Accessed July 16, 2015.

2. Porter ME. Value-based health care delivery. Talk presented at: 2015 ASCO Annual Meeting: opening session with Conquer Cancer Foundation top donors recognition. http://meetinglibrary.asco.org/content/106525?media=vm. Accessed July 16, 2015.

3. Schnipper LE, Davidson NE, Wollins DS, et al. American Society of Clinical Oncology Statement: a conceptual framework to assess the value of cancer treatment options. J Clin Oncol. 2015. doi:10.1200/JCO.2015.61.6706.

4. Oncology Care Model. CMS website. http://innovation.cms.gov/initiatives/Oncology-Care/. Accessed July 2, 2015.

5. NCCN clinical practice guidelines in oncology: breast cancer. National Comprehensive Cancer Network website. http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed July 2, 2015.

6. Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN. The Her2 receptor and breast cancer: ten years of targeted anti-Her2 therapy and personalized medicine. Oncologist. 2009;14(4):320-368.

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