Abstract
Background
Diagnostic tests, including US Food and Drug Administration (FDA)-approved tests and laboratory-developed tests, are frequently used to guide care for patients with cancer, and, recently, have been the subject of several policy discussions and insurance coverage determinations. As the use of diagnostic testing has evolved, stakeholders have raised questions about the lack of standardized test performance metrics and the risk this poses to patients.
Objectives
To describe the use of diagnostic testing for patients with advanced non–small-cell lung cancer (NSCLC), to analyze the utilization of FDA-approved versus laboratory-developed diagnostic tests, and to evaluate the impact of existing regulatory and coverage frameworks on diagnostic test ordering and physician treatment decision-making for patients with advanced NSCLC.
Methods
We conducted a 2-part study consisting of an online survey and patient chart review from March 1, 2019, to March 25, 2019, of physicians managing patients with advanced NSCLC. Respondents qualified for this study if they managed at least 5 patients with advanced NSCLC per month and had diagnosed at least 1 patient with advanced NSCLC in the 12 months before the survey. A total of 150 physicians completed the survey; before completing the survey, they were instructed to review between 4 and 8 charts of patients with stage IV NSCLC from their list of active patients.
Results
A total of 150 practicing oncologists who manage patients with advanced NSCLC responded to the survey and reviewed a total of 815 patient charts. Of these 815 patients, 812 (99.6%) were tested for at least 1 biomarker, including 73% of patients who were tested for EGFR, 70% tested for ALK, 58% tested for BRAF V600E, and 38% of patients tested for ROS1, by FDA-approved diagnostic tests. In all, 185 (83%) patients who tested positive for EGFR and 60 (83%) patients who tested positive for ALK received an FDA-approved targeted therapy for their biomarker. A total of 98 (65%) physicians responded that the patient's insurance coverage factored into their decision to order diagnostic tests and 69 (45%) physicians responded that cost or the patient's insurance coverage could influence them not to prescribe an indicated targeted therapy.
Conclusion
The survey results indicate that diagnostic testing has become routine in the treatment of patients with advanced NSCLC, the use of FDA-approved diagnostic tests has increased, and insurance coverage and cost influence patient access to diagnostic testing as well as to targeted treatment options.
Keywords: advanced NSCLC, diagnostic tests, FDA-approved tests, insurance coverage, laboratory-developed tests, lung cancer biomarkers, physician decision-making, targeted therapies
Molecular diagnostic tests are increasingly being used to guide care for patients with cancer, as the understanding of how different biomarkers contribute to tumor growth improves, technologies allowing for the simultaneous evaluation of multiple tumor alterations become available, and a growing number of transformative biomarker-targeted therapies are developed.1 These targeted therapies have proved beneficial to many patients with cancer, and in certain cancer indications, including EGFR mutation–positive advanced non–small-cell lung cancer (NSCLC), these therapies have led to notable improvements in patient outcomes, such as 5-year survival rates and progression-free survival.2
KEY POINTS
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Diagnostic tests are increasingly being used to guide the diagnosis and treatment of patients with advanced non–small-cell lung cancer.
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Of the 815 patients whose charts were reviewed, 812 (99.6%) patients were tested for at least 1 biomarker.
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A total of 73% of patients tested for EGFR mutations, 70% tested for ALK rearrangements, 58% tested for BRAF V600E mutations, and 38% tested for ROS1 rearrangements received FDA-approved diagnostic tests.
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A total of 83% of patients who tested positive for EGFR and 83% of those who tested positive for ALK received an FDA-approved targeted therapy indicated for their biomarkers.
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Overall, 98 (65%) physicians indicated that the patient's insurance coverage factored into their decision-making when ordering diagnostic tests.
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Insurance coverage and cost were cited most frequently as factors that influence a provider's decision to prescribe a targeted therapy.
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Optimized regulatory and coverage frameworks for diagnostic tests and biomarker-targeted therapies are critical to an oncology patient's access to care.
Recognizing the growing evidence that supports the use of diagnostic tests to identify appropriate therapies for patients with advanced NSCLC, leading organizations, such as the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology, the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology, have established clinical guidelines that universally recommend diagnostic testing for most patients with advanced or metastatic NSCLC.3–5 These guidelines are intended for use by oncologists in the diagnosis and treatment decision-making processes.3–5
In addition, payers such as the Centers for Medicare & Medicaid Services (CMS), the largest payer in the US healthcare system, have recognized the importance of molecular diagnostic tests to their patient populations. In March 2018, CMS released a coverage determination in which US Food and Drug Administration (FDA)-approved or -cleared diagnostic tests that use next-generation sequencing technologies were deemed reasonable and necessary for patients with recurrent, relapsed, refractory, metastatic, or advanced stage III or IV cancer.6 This decision ensured consistent coverage policy of FDA-approved and FDA-cleared diagnostic tests for Medicare patients at the national level. Recent data also suggest that these multigene panels may be more cost-effective than single-marker genetic tests.7
Diagnostic test results must be accurate, reliable, and clinically meaningful for patients to reap the benefits of precision medicine and biomarker-targeted therapies. Currently, the performance metrics of diagnostics are evaluated under a bifurcated regulatory system. The FDA was given authority to regulate all in vitro diagnostics as medical devices under the 1976 Medical Device Amendments to the Federal Food, Drug, and Cosmetic Act.8 However, the agency has generally exercised discretion and has not enforced the device provisions of this legislation consistently on the subset of in vitro diagnostics (referred to as laboratory-developed tests); this is because, historically, laboratory-developed tests used relatively simple technology and have had limited availability.8,9
Instead, laboratory-developed tests have been regulated under the Clinical Laboratory Improvement Amendments (CLIA) program, which is overseen by CMS.10 In contrast to rigorous FDA review, which requires demonstrations of analytical and clinical validity, the CLIA certification primarily assesses a laboratory's ability to properly conduct tests through protocol adherence and personnel qualification, but typically not the performance metrics of the test itself.10
Consequently, as the practice of medicine has evolved, and diagnostic tests have become increasingly complex and vital to clinical care, stakeholders such as patient advocacy organizations, congressional legislators, and the FDA have raised questions about the lack of standardized performance metrics for FDA-approved tests and for laboratory-developed tests, emphasizing the risk that this lack of standardization poses to patients.11
In fact, after identifying multiple problems with the performance of several high-risk laboratory-developed tests in 2010, the FDA announced its intent to reconsider its policy of enforcement discretion and took several subsequent actions. These actions included the development of draft guidance that outlined an approach to laboratory-developed test oversight in 2014, the publication of a report with 20 case studies that documented the public health impact of problematic laboratory-developed tests in 2015, and the release of a discussion paper on such tests in 2017.9,11,12
In December 2018, congressional leaders working with the FDA and other stakeholders, including clinical laboratories, diagnostic test manufacturers, trade associations, and patient advocacy groups, released draft legislation aimed at establishing a uniform regulatory framework for all diagnostic tests under the authority of the FDA, with the intent of reducing the lack of standardization and inconsistent regulatory requirements for FDA-approved tests and laboratory-developed tests.13
This draft legislation was updated to incorporate extensive comments from the FDA and the broader community and was introduced to the US House of Representatives in early 2020, but its legislative path forward remains unclear.14
As part of our 2015 national survey of oncologists who managed patients with advanced NSCLC, we explored the use of FDA-approved diagnostic tests and laboratory-developed tests.15 The findings from this original survey indicated that most patients with advanced NSCLC received testing for EGFR mutations and ALK rearrangements, with testing for EGFR more frequently performed in privately owned, academic, and community-based treatment settings using laboratory-developed tests, and testing for ALK evenly split between laboratory-developed tests and FDA-approved diagnostics across these settings. This utilization of different tests within the same treatment setting raised concerns that an unknown degree of variability could exist between tests with the same intended use.15
In the period since this original survey was conducted, tests have increased in complexity and have become more widely available, policy discussions have evolved, and major coverage determinations have been made; therefore, a new landscape analysis is warranted.
Our current study updates the original survey data15 by investigating the use of FDA-approved tests and laboratory-developed tests based on a 2019 national survey of oncologists who managed patients with advanced NSCLC. In addition, this study includes survey questions regarding the factors that influence the diagnostic test ordering and treatment decision-making practices of physicians who manage patients with advanced NSCLC under current regulatory and coverage frameworks.
Methods
The study sample was based on a national panel of oncologists maintained by M3 Global Research. This panel includes more than 1000 physicians and is broadly representative of all oncologists in the United States across the demographic dimensions of region and years in medical practice. Study invitations were sent to all oncologists within the M3 panel. Respondents qualified for this study if they managed at least 5 patients with advanced NSCLC per month and had personally diagnosed at least 1 patient with advanced NSCLC in the 12-month period before the survey fielding (March 2018-February 2019).
The study consisted of 2 parts: a short survey and a patient chart review. A total of 150 physicians completed the study, translating to a response rate of 14%. The participants were offered an industry-standard honorarium as compensation for their time to complete the study. The study was administered online and was fielded from March 1, 2019, to March 25, 2019.
A data collection instrument was developed to capture deidentified information on patients with stage IV NSCLC in the United States for use in the chart review portion of the study. Based on a similar instrument fielded in 2015, we made updates to reflect new treatment and diagnostic test options that were available at the time of the study.
Before completing the survey, responding physicians were instructed to choose between 4 and 8 patients with stage IV NSCLC from their list of active patient charts. To facilitate the selection of random charts, oncologists were instructed to identify patients based on the assignment of random letters to correspond with the first letter of the patients' last names. The patient charts were required to have been active within the practice during the past 12 months.
Patient information, including age, weight, sex, ethnic origin, concomitant conditions, insurance type, smoking status, diagnosis year, genetic testing information, and all treatment lines, was recorded by physicians using the data collection instrument for each randomly selected patient chart. A total of 815 patient charts were included in the study, which reflected the practices of 150 responding oncologists who managed patients with advanced NSCLC.
Data Analysis
All survey data, including the identities of the responding physicians, were analyzed in aggregate and were completely anonymized. When the specific genetic test types were unknown to the responding physician, consent was obtained to contact the affiliated hospital pathology laboratory. Follow-up phone calls were made in these instances to determine which genetic testing platform or external testing services a specific hospital uses. The data were analyzed across all patients, as well as across the histologic subtypes of advanced NSCLC.
Key patient demographics, such as patient insurance type and practice setting, were also analyzed for patterns in genetic testing. Patients were included in the analysis of the use of FDA-approved and laboratory-developed tests if they were diagnosed with advanced NSCLC after the first FDA approval of a diagnostic test for a given NSCLC-related mutation, and if their test type could be determined. Patients who were diagnosed with advanced NSCLC before the first FDA approval of a diagnostic test for a given NSCLC-related mutation and whose test type could not be determined were excluded from this analysis.
The analysis of insurance type was limited to patients with private insurance or with Medicare coverage. Patients with Medicaid, military insurance, self-insurance, no insurance, or unknown insurance types were excluded because of low sample sizes or because of the possibility of inherent confounding variables in these populations.
Statistical Analysis
All subgroup differences in proportions were tested using a chi-square analysis. Post-hoc pairwise comparisons used a Bonferroni correction to reduce the risk for type 1 errors. The pairwise comparisons were tested for significance at the .05 level. All statistical analysis was performed using IBM SPSS Statistics Version 20.0 (IBM; Armonk, NY).
Results
The study physician and patient characteristics are presented in Table 1. Our sample of physicians was broadly representative of oncology physicians across factors of interest such as years in practice and geographic region. In addition, the patient population included in our chart review was representative of the wider population of patients with advanced NSCLC across factors of interest such as age and histologic subtype.16
Table 1.
Characteristics of Physicians Who Completed the Survey and Patient Chart Review and Distribution of Patient Population Across Factors of Interesta
| Physician characteristics | Responding physicians, N (%) | Patient characteristics | Patient charts, N (%) |
|---|---|---|---|
| Sex | Sex | ||
| Female | 27 (18) | Female | 320 (39) |
| Male | 122 (81) | Male | 495 (61) |
| Unknown | 1 (1) | Age-group | |
| Years in practice | 18–39 yrs | 25 (3) | |
| <10 yrs | 34 (23) | 40–64 yrs | 294 (36) |
| 10–19 yrs | 43 (29) | ≥65 yrs | 496 (61) |
| 20–29 yrs | 23 (15) | Geographic region | |
| ≥30 yrs | 49 (33) | Midwest | 190 (23) |
| Unknown | 1 (1) | Northeast | 184 (23) |
| Practice type | South | 209 (26) | |
| Academic center | 57 (38) | West | 167 (20) |
| Community-based center | 29 (19) | Unknown | 65 (8) |
| Private clinic | 64 (43) | Cancer center setting | |
| Region | Academic center | 341 (42) | |
| East North Central | 28 (19) | Community-based center | 151 (18) |
| East South Central | 5 (3) | Private clinic | 323 (40) |
| Middle Atlantic | 28 (19) | Insurance coverage | |
| Mountain | 9 (6) | Medicaid | 95 (12) |
| New England | 5 (3) | Medicare | 316 (39) |
| Pacific | 21 (14) | Medicaid + Medicare | 17 (2) |
| South Atlantic | 25 (17) | Private | 325 (40) |
| West North Central | 7 (5) | Other | 45 (5) |
| West South Central | 11 (7) | Unknown | 17 (2) |
| Unknown | 11 (7) | Ethnicity | |
| Practice ownership | Caucasian | 461 (56) | |
| Physician owned | 78 (52) | African American | 181 (22) |
| Hospital owned | 72 (48) | Asian | 104 (13) |
| Other | 0 (0) | Hispanic | 63 (8) |
| Payer distribution (by patient's coverage) | Other | 6 (1) | |
| Majority Medicaid | 13 (9) | Histologic subtypes | |
| Majority Medicare | 62 (41) | Squamous-cell carcinoma | 214 (26) |
| Majority private | 47 (31) | Adenocarcinoma | 536 (66) |
| Mix | 28 (19) | Other type | 65 (8) |
| Smoking status | |||
| Current smoker | 183 (22) | ||
| Past smoker | 405 (50) | ||
| Passive smoker | 48 (6) | ||
| Never smoked | 172 (21) | ||
| Unknown | 7 (1) | ||
Information on 815 patients provided by 150 responding physicians.
Biomarker testing rates among patients selected in the chart review portion of our study were examined. Of the 815 patients with advanced NSCLC in this study, 812 (99.6%) patients were tested for at least 1 mutation. A total of 669 (82%) patients were tested for EGFR mutations, 586 (72%) for ALK rearrangements, 298 (37%) for BRAF V600E mutations, and 380 (47%) for ROS1 rearrangements. Other biomarkers were tested at lower frequencies. Of the 601 patients who were not classified as having squamous-cell carcinoma, 203 (34%) were tested for all 4 of these mutations.
The use of FDA-approved diagnostic tests for EGFR mutations, ALK rearrangements, BRAF V600E mutations, and ROS1 rearrangements across treatment setting and insurance type is shown in Table 2. The differences in the use of FDA-approved diagnostic tests across treatment settings were significant (P <.05), indicating that the setting in which a patient receives treatment may influence whether he or she receives an FDA-approved test or a laboratory-developed test. Specifically, the difference in the use of FDA-approved tests for EGFR mutations between the academic (65%) and private (82%) practice settings was determined to be significant (P <.05).
Table 2.
Use of FDA-Approved versus Laboratory-Developed Diagnostic Tests Across Patient Treatment Settings and Insurance Types
| Patient treatment setting |
Patient insurance type |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| Test used, by molecular abnormalities | Total sample, N (%) | Academic center, N (%) | Community-based center, N (%) | Private clinic, N (%) | Medicare only, N (%) | Private, N (%) | Medicaid only, N (%) | Medicare + Medicaid, N (%) | Other, N (%) |
| EGFR | |||||||||
| FDA-approved | 273 (73) | 96 (65) | 47 (69) | 130 (82) | 103 (75) | 103 (73) | 36 (72) | 5 (56) | 26 (72) |
| Laboratory-developed | 101 (27) | 51 (35) | 21 (31) | 29 (18) | 35 (25) | 38 (27) | 14 (28) | 4 (44) | 10 (28) |
| ALK | |||||||||
| FDA-approved | 219 (70) | 78 (56) | 40 (71) | 101 (86) | 85 (71) | 85 (71) | 28 (70) | 4 (50) | 17 (61) |
| Laboratory-developed | 95 (30) | 65 (44) | 16 (29) | 17 (14) | 34 (29) | 34 (29) | 12 (30) | 4 (50) | 11 (39) |
| BRAF V600E | |||||||||
| FDA-approved | 75 (58) | 22 (44) | 15 (48) | 38 (79) | 24 (57) | 32 (59) | 16 (73) | 1 (33) | 2 (25) |
| Laboratory-developed | 54 (42) | 28 (56) | 16 (52) | 10 (21) | 18 (43) | 22 (41) | 6 (27) | 2 (67) | 6 (75) |
| ROS1 | |||||||||
| FDA-approved | 62 (38) | 24 (41) | 6 (18) | 32 (44) | 20 (35) | 27 (42) | 11 (42) | 1 (20) | 3 (30) |
| Laboratory-developed | 101 (62) | 34 (59) | 27 (82) | 40 (56) | 37 (65) | 38 (58) | 15 (58) | 4 (80) | 7 (70) |
NOTE: This table only includes information about patients for whom we were able to identify whether their diagnostic test was FDA-approved or laboratory-developed. Differences in the use of FDA-approved tests for EGFR mutations between the academic (65.3%) and private (81.8%) practice settings were significant (P <.05), based on chi-square tests. Differences in the use of FDA-approved tests for ALK rearrangements between the academic (55.7%) and private (85.6%) practice settings were significant (P <.05), based on chi-square tests.
FDA indicates US Food and Drug Administration.
The differences in the use of FDA-approved tests for BRAF V600E mutations between the academic (44%) and private (79%) practice settings were also significant (P <.05). The differences in the use of FDA-approved tests for ROS1 rearrangements between the community-based (18%) and private (44%) practice settings were significant as well (P <.05). No significant differences were observed between patients with private insurance and patients with Medicare coverage.
The receipt of an appropriate targeted therapy among patients who tested positive for an actionable biomarker was evaluated for EGFR mutations and ALK rearrangements across the treatment settings and insurance types. Therapies were deemed “appropriate” in this analysis if they were FDA-approved for advanced NSCLC, and if they targeted the biomarker(s) for which a patient tested positive.
Of the 669 patients who were tested for EGFR mutations, 223 (33%) tested positive for that mutation. In all, 185 (83%) of these patients received a targeted therapy indicated for patients with EGFR-positive advanced NSCLC. Similarly, of the 586 patients who were tested for ALK rearrangements, 72 (12%) tested positive for that mutation. A total of 60 (83%) of these patients received a targeted therapy indicated for patients with ALK-positive advanced NSCLC.
The differences in the use of an appropriate targeted therapy for patients testing positive for EGFR mutations between the academic (92%) and community-based (75%) practice settings were determined to be significant (P <.05). The difference in the use of an appropriate targeted therapy for patients testing positive for EGFR mutations between the academic (92%) and private (77%) practice settings was also significant (P <.05).
These significant differences indicate that a patient's treatment setting may influence whether he or she receives a targeted treatment. The use of an appropriate targeted therapy for patients testing positive for ALK rearrangement was significant overall (P <.05), but there were no significant differences in the pair-wise comparisons. No significant differences were observed between patients with private insurance and those with Medicare coverage.
A total of 66 (44%) physicians who responded to the survey indicated that the availability of targeted therapies influences their decision to order diagnostic tests for patients with advanced NSCLC. In all, 98 (65%) physicians indicated that the patient's type of insurance coverage factors into their decision to order diagnostic tests for patients with advanced NSCLC (Figure Part A).
Figure. Factors Influencing Use of Diagnostic Tests and Prescription of Targeted Therapies: Selected Physician Questionnaire Responses.
aThis survey question was open-ended and responses were coded into the categories listed.
CMS indicates Centers for Medicare & Medicaid Services; FDA, US Food and Drug Administration; NSCLC, non–small-cell lung cancer.
A total of 107 (71%) respondents indicated that they were aware of the CMS next-generation sequencing coverage determination (Figure Part B), and 74 (69%) of those 107 physicians indicated that this determination increased the frequency of diagnostic tests that they order for patients with advanced NSCLC (Figure Part C). In all, 149 (99%) physicians indicated that they are confident that diagnostic tests yield high-quality data about their patients with advanced NSCLC.
A total of 69 physicians (45%) responded that in a case when a diagnostic test indicated a specific therapy for a patient with advanced NSCLC, cost issues or the patient's insurance coverage could influence them not to prescribe the indicated therapy (Figure Part D). The full physician questionnaire can be found in the Appendix (available at www.AHDBonline.com). Selected questionnaire responses are shown in the Figure.
Discussion
Given the increasing importance of molecular diagnostic tests and targeted therapies in the diagnosis and treatment of patients with cancer, we examined the diagnostic test ordering and treatment decision-making practices of physicians who are managing patients with advanced NSCLC under the current federal regulatory and healthcare coverage frameworks. Our analysis of 150 physician survey responses and 815 patient records produced 3 key findings.
First, our findings indicate that diagnostic testing has become routine in the diagnosis of and treatment decision-making for patients with advanced NSCLC. The survey respondents reported that almost all patients included in the chart review received at least 1 diagnostic test, which is consistent with previous findings in the literature that indicate high rates of diagnostic testing in patients with lung cancer.17–20
In line with evidence-based clinical practice guidelines issued by the NCCN,5 we observed that most patients were tested for EGFR mutations and ALK rearrangements, and that the testing rates differed across the histologic subtypes. Although most patients were tested for these individual genetic markers, few patients received the NCCN-recommended comprehensive biomarker testing for their subtypes,5 indicating that barriers to comprehensive biomarker testing may still exist.
In addition, our survey highlights that frameworks for the appropriate insurance coverage of diagnostic tests and targeted therapies are important to the access of care for patients with advanced NSCLC. The survey respondents indicated that insurance coverage influences their decision to order diagnostic tests for patients with advanced NSCLC. Furthermore, insurance coverage and cost were the most frequently reported factors that influenced a physician not to prescribe an indicated therapy.
Although we did not observe significant differences in the ordering of diagnostic tests and in the prescription of targeted therapies across the insurance types it is likely because, as a result of sample size concerns, our analyses were limited to patients with private insurance and Medicare, and the value of diagnostic tests and targeted therapies is widely acknowledged by these payers. Further examination of the impact of insurance type on a patient's access to diagnostic tests and targeted therapies is warranted, and if inequities in access to care are observed, intervention may be required at the societal and governmental levels.
Finally, we observed a shift toward the use of FDA-approved diagnostic tests since the publication of our 2015 survey,15 but the magnitude of this shift differed across the treatment settings. In our 2015 survey, only 13% of patients tested for EGFR and 51% of patients tested for ALK received FDA-approved diagnostic tests,15 compared with 73% and 70%, respectively, in our current survey (Table 2). This shift may indicate that physicians and, ultimately, pathologists value FDA regulation as well as newly approved technologies, such as next-generation sequencing panels, which were approved for use in this population after 2015.
The differences in the magnitude of this shift across the treatment settings may reflect, in part, that physicians in the academic setting preferentially use tests developed by their individual institutions. Our results also suggest that the overall increase in the use of FDA-approved tests may be explained by the increasing number of diagnostic assays approved by the FDA (eg, 2 tests approved in 2015 for EGFR vs 4 in 2019; 1 test approved in 2015 for ALK vs 3 in 2019) and the length of time since the initial FDA approval of a diagnostic test for a given mutation (eg, the first EGFR mutation test was approved in 2013; in 2015, that test had been on the market for 2 years vs 6 years in 2019).
Policy Implications and Recommendations
Based on the results of this 2-part study consisting of a survey and chart review, we recommend 2 policy changes to ensure patient access to high-quality, well-validated diagnostic tests and to their indicated biomarker-targeted therapies.
First, we recommend that as legislators and other stakeholders continue to work toward improving the current regulatory system for the benefit of patients, they prioritize the development of a predictable regulatory framework that fosters and encourages innovation while maintaining uniform oversight. Although we observed a shift toward the use of FDA-approved tests in our survey, a significant number of patients with advanced NSCLC still received molecular assessments that are subject to regulatory requirements different from those pursuing FDA premarket review.
However, this study did not seek to address the relative quality of laboratory-developed tests and FDA-approved diagnostic tests, and further research on potential variability in performance metrics and comparative outcomes is warranted. An improved framework should maintain the FDA's standards for analytical and clinical validity but not impose an excessive burden on stakeholders involved in diagnostic test innovation, such as academic laboratories that have voiced concerns that seeking FDA approval would be onerous and expensive.
Second, we recommend that as payers consider future coverage decisions, in the absence of a uniform regulatory framework, they develop a minimum set of performance characteristics necessary to support determinations of coverage for diagnostic tests. Because diagnostic test results are frequently used in treatment decision-making processes, it is critical that accurate results are produced to prevent patients from being exposed to nonefficacious treatments and the unnecessary toxicities that would result from inappropriate identification of candidates for treatment.
As our survey demonstrated, physician decision-making is affected by insurance coverage, and the latest shifts toward the use of FDA-approved diagnostic tests coincided with the recent CMS coverage determination, which indicates that coverage frameworks may have the potential to alter physicians' prescribing patterns. Furthermore, the continued coverage of biomarker-targeted therapies and mechanisms for rapidly incorporating new diagnostic test and drug approvals into coverage frameworks are essential to preserve patient access.21
Limitations
This study has several limitations. First, this survey focused on oncologists, not pathologists. Although pathologists may have access to more diagnostic test–related information, oncologists were more appropriate for this study because our goals were to evaluate the use of diagnostic tests for patients with advanced NSCLC and to identify factors influencing physician decision-making under existing regulatory and coverage frameworks.
In addition, our study was not designed to address the comparative outcomes of patients who were tested with laboratory-developed tests versus FDA-approved tests.
Furthermore, as with most surveys, the potential for response bias and for nonresponding physicians bias exists.
The potential impact of confounders, such as a patient's inability to receive a diagnostic test because of insufficient tissue, is unknown.
Finally, a portion of the patient records (and associated pathology reports) did not include information on the type of test used to detect lung cancer mutations, even after follow-up phone calls, and had to be excluded from further analysis, including 295 (44%) patients who were tested for EGFR mutations, 272 (46%) patients who were tested for ALK rearrangements, 169 (57%) patients tested for BRAF V600E mutation, and 217 (57%) patients tested for ROS1 rearrangements.
Conclusion
Molecular diagnostic tests and biomarker targeted therapies are routinely used in oncology care and will continue to drive the concept of precision medicine forward. Our study presents novel survey and chart review data that illustrate the routine use of diagnostic tests in the treatment of patients with advanced NSCLC and demonstrate an increase in the use of FDA-approved diagnostic tests. We also identify factors, such as insurance coverage and cost, that influence physicians' diagnosis and treatment decision-making processes. Together, these findings illustrate that optimized regulatory and coverage frameworks are critical to an oncology patient's access to care.
Author Disclosure Statement
Ms Wempe, Dr Stewart, Dr Glass, Dr Lasiter, Dr Vega, Dr Allen, Dr Sigal, and Ms Ramamurthy have no conflicts of interest to report.
Contributor Information
Madison M. Wempe, Research Associate, Friends of Cancer Research, Washington, DC.
Mark D. Stewart, Vice President, Science Policy, Friends of Cancer Research, Washington, DC.
Daniel Glass, Managing Director, Global Market Research, Deerfield Management, New York, NY.
Laura Lasiter, Director, Health Policy, Friends of Cancer Research, Washington, DC.
Diana Merino Vega, Director, Research Partnerships, Friends of Cancer Research, Washington, DC.
Nisha Ramamurthy, Summer Intern, Friends of Cancer Research, Washington, DC.
Jeff Allen, President and CEO, Friends of Cancer Research, Washington, DC.
Ellen V. Sigal, Chairperson and Founder, Friends of Cancer Research, Washington, DC.
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