Identification of gaps in quality measures within cancer immunotherapy

The first step was to assess the landscape of currently available quality data related to cancer immunotherapy through peer-reviewed literature, professional organizations, and other established quality networks. Through a review of SITC, National Comprehensive Cancer Network (NCCN), ASCO clinical guidelines, among others, measurement opportunities were identified across the cancer care trajectory for patients receiving cancer immunotherapy. This included considerations related to treatment decision-making at the time of initial cancer diagnosis through active treatment, recognition and management of irAEs, and initial care outcomes as well as long-term survivorship issues. The panel recognized that only a few quality measures exist that are directly related to the use of cancer immunotherapy. ‘Direct’ measures include those specifically assessing the use of cancer immunotherapy in clinical care. ‘Indirect’ measures include those assessing clinical care for general cancer populations that are inclusive of patients treated with immunotherapy.

Professional society quality programs, including the ASCO QOPI and the American College of Surgeons CoC, have developed and implemented quality measures related directly to the use of cancer immunotherapy that primarily assess suitable prescribing methods for certain therapies, ordering of appropriate testing of specific biomarkers, and utilization of certification programs, such as ASCO QOPI.15–17 Importantly, professional society quality programs have not yet incorporated clinical outcome measures. In Medicare value-based payment and reporting programs, the quality measures are predominantly indirect measures and focus on achievement of general outcomes (eg, 30-day unplanned readmissions) (table 1). There is a lack of similar quality measures for novel cancer immunotherapies such as immune checkpoint inhibitors or chimeric antigen receptor (CAR)-T therapies. In addition, there are other key cancer programs, such as the OCM and the PPS-Exempt Cancer Hospital Quality Reporting program, which do not incorporate any cancer immunotherapy quality measures or standards.

Outcome measures for the assessment and implementation of evidence-based interventions (ASCO/NCCN) for adverse events (AE) related to immune checkpoint inhibitors have been developed by the ONS and Premier.18 ONS and Premier collaborated to offer outcome quality measures that assess patient experience, quality of life, and early identification of symptoms and include the use of evidence-based interventions related to cancer immunotherapy. These two measures were released through MIPS reporting as well as for practice or institutional quality improvement purposes in 2019. Despite the availability of these measures, there are still gaps in outcome and evidence-based management of symptoms that capture patient experience and quality of life.18 Table 2 provides examples of available quality measures in professional society sets that relate directly or indirectly to cancer immunotherapy, which were also considered by the panel. The NQF, Center for Medicare and Medicaid Innovation (CMMI), and Core Quality Measures Collaborative (CQMC) (The CQMC is a broad-based coalition of health leaders convened by America’s Health Insurance Plans, the CMS, and the NQF. CQMC collaborates to recommend core sets of measures by clinical area to assess quality of care. More information can be found here: http://www.qualityforum.org/cqmc/) have separately identified measure gaps for general cancer populations.14 19–22

High-priority gaps in this population include:

• Survival rates.

• Access to hospice.

• Five-year cure rate.

• Quality of life/patient-reported outcomes.

• Shared decision-making.

• Overuse/underuse.

• Medication reconciliation.

• Clinical trial access.

• Functional status.

• Mortality rates.

• Goal setting.

• Post-treatment complication rates.

The gaps identified by NQF, CMMI, and CQMC above are cross-cutting and apply broadly to cancer care. ASCO, Cancer Support Community, the Community Oncology Alliance, and the Patient Advocate Foundation explored opportunities to advance cancer quality in the era of innovative treatments and prioritized survival and shared decision-making, among others listed below, as areas for future measure development23:

• Survival.

• Shared decision-making.

• Social, emotional and spiritual health.

• Genomic sequencing informing biomarker-based treatment selection.

• Accuracy of diagnosis and comprehensive treatment.

• Screening/management for depression.

Efforts are underway to close gaps in cross-cutting cancer clinical outcome measures. Of note, the NQF Incubator is exploring measure development and testing for lung cancer and melanoma survival measures and a lung cancer patient-reported outcome performance measure.24

Based on the output of SITC’s gap analysis process, gaps in measures were also identified in relation to the care model:

• First, second, or third-line cancer immunotherapy prescribing, including biomarker testing.

• Pretreatment evaluation and assessment of longer term clinical outcomes (eg, response duration, treatment-free survival/remission, survival).

• Monitoring and management of irAEs.

Gaps impacting cancer immunotherapy care delivery were also identified through a review of the literature:

• Knowledge and adoption of immunotherapy: There is significant variability in the adoption of immunotherapy by oncology practices.25 Along with the variation in implementation and use of cancer immunotherapy, there is a gap in knowledge and understanding of immunotherapy treatments among oncology providers. In 2017, a survey conducted by the Association of Community Cancer Centers reported that only 24% of respondents reported deep familiarity with checkpoint inhibitors, 32% with monoclonal antibody therapy, and 17% with combination treatment regimens.26 Furthermore, data on CAR-T cell therapies and oncolytic viruses are lacking.

• Identifying p seudo progression or h yper p rogression of t umors: Quality issues related to the accuracy in identifying tumor ‘pseudo’-progression or ‘hyper’-progression related to immunotherapy were identified. These only occur in a subset of cancer immunotherapy patients but can have implications for decisions to continue or discontinue therapy and have subsequent effects on the long-term health outcomes for a patient.27 28 These unusual patterns of response also add complexity to defining when to continue or discontinue therapy.

• Communication and c oordination of c are: Quality issues in cancer immunotherapy relate to the monitoring and management of clinical care. A 2017 study concluded that only 37% of healthcare professionals notify the primary cancer team of their decision to treat the patient with immunotherapy 80%–100% of the time, and most healthcare professionals notify the primary cancer team less than 60% of the time.29

• Monitoring and m anagement of AE s: Only 49% of healthcare professionals are comfortable with recognizing and managing irAEs.29 The issues related to the early recognition and management of irAEs expose a gap and need for education.30 31

• Use of p atient- r eported o utcome m easures ( PROM ): The routine use of PROMs is recognized in the literature as an important strategy to evaluate treatment-related toxicities, evaluate functional declines and/or improvements associated with irAE management.32

Patient safety

Proposed quality measure: t imely and a ppropriate m anagement of i mmune-related c olitis in patients with c ancer t reated with i mmune c heckpoint i nhibitors

The group recognized the many types of irAEs can occur with cancer immunotherapy, and agreed the field would benefit from gathering further data and generating benchmarks for individual AEs, such as immune-related dermatitis, colitis, pneumonitis, hypophysitis, hepatitis, and others. Thus, the patient safety breakout group considered the recognition and management of AEs, with an emphasis on identification and management that can lead to improved outcomes, as an important quality measure concept since most existing measures are pure process measures. The group recognized that there are published data supporting the hypothesis that timely management of care and/or rapid specialist referral for immune-related colitis results in beneficial outcomes for patients.33 As such, the group selected diarrhea (ie, immune-related colitis) for rapid diagnosis and treatment. Colitis is a common, potentially serious, and well-characterized AE during immunotherapy that can be easily identified and monitored, and which likely could result in improved clinical outcomes if mismanagement that results in serious morbidity and mortality is avoided.

Diarrhea is one of the four AEs (diarrhea, rash, fatigue, pruritus), which the ONS and Premier included in their CMS-approved quality measure ‘Assessment for and Management of Immune-Related Adverse Events During Cancer Treatment with Checkpoint Inhibitors’. ONS currently has a grading system in place for diarrhea but it does not include the length of time of the management and/or treatment, which highlight gaps and needed areas of clarification within existing guidelines. Panelists discussed key considerations for the measure concept but generally agreed that standardized and validated grading systems are lacking. A goal of the proposed measure concept would be to reflect an evidence and guideline-based definition of timeliness. The panelists also indicated the potential utility of patient self-reporting for immunotherapy AEs to reflect overall daily health and management.34

Person and family-centered care

Proposed quality measure: g oal -c oncordant c are: p atient- r eported e stablishment of c are g oals and a ssessment t hat goals w ere m et

The ‘Patient-Reported Establishment of Care Goals and Assessment That Goals Were Met’ measure concept was recommended to assess an essential element of patient experience of care, through recognizing individual patient goals and engagement in the shared decision-making process. For example, developing goal-concordant care of a patient experiencing an AE related to immune checkpoint inhibitors could be included in goal setting and attainment measures. The intention of this measure is to first evaluate the communication of initial immunotherapy treatment options and associated side effects and subsequent goal-concordant care between the patient and the physician prior to treatment initiation as well as throughout the care trajectory. A second intention is to measure whether patient care goals were acknowledged and considered. Differing perspectives on shared decision-making include issues of informed consent, types of patient expectations, quality of life, and symptom management, and panelists aimed to create a measure concept which can be continuously reassessed to account for varying priorities throughout the duration of care. The measure concept would require a patient survey covering three concepts:

1. Did your clinician discuss your expectations/preferences up front and set goals with you?

2. Was there continuous shared decision-making based on response to treatment, evolution of scientific and clinical knowledge, and others?

3. Were the defined goals respected and considered throughout the process?

Significant limitations exist for establishing this type of quality measure. First, while measuring goal-concordant care is a quality measure for seriously ill patient populations,35 targeted goal-setting quality measures have not been developed for use in pretreatment cancer populations. Second, data collection may be challenging. Patient self-reporting would be a gold standard occurring either at the point of care (eg, electronic tablets in the waiting room) or independently (ie, mailed or phone survey at the patient’s home). While some care-planning quality measures in this area focus on electronic health record (EHR) documentation by clinicians, panelists determined that a clinician-facing EHR structured data element (ie, ‘checkbox’) documenting the occurrence of shared decision-making conversations would be insufficient since there is often a discrepancy between what the patient and the physician consider to be shared decision-making and unaudited attestation measures lack sufficient validity.36 Finally, the unique issues of this patient population add additional measurement challenges. Appropriate timing of the measurement window for the collection of patient self-reported data may also be challenging, as treatment decisions are made quickly based on diagnostic information and second-line and higher treatment options may happen over several weeks or even months. Also, as with any patient-facing assessment, patient burden to answer these questions should always be considered. Given these administrative and timing challenges, panelists discussed the potential utility of piloting this measure concept as a feasibility study in a cancer immunotherapy clinical trial ahead of real-world deployment. Another approach would be to use a validated cancer-focused patient experience of care measure to benchmark communication and shared decision-making at the provider level. The Consumer Assessment of Healthcare Providers and Systems (CAHPS) Cancer Care Survey was developed to provide a standardized measure of patient experience of care during cancer treatments.37 ,38 CAHPS Cancer Care was developed to be valid and reliable for cancer treatment modalities, including immunotherapy, and clinic type (eg, cancer center, community clinic, and so on). CAHPS Cancer Care includes quality measures on general clinician–patient communication and shared decision-making.39 The CAHPS’ shared decision quality measure includes questions such as: ‘Doctor asked patient what cancer treatment choice was best for him/her’ (three response options: (1) yes, definitely; (2) yes somewhat; (3) no), the communication measure asks cancer patient agreement (5-point Likert scale: never to always): ‘Cancer care team showed respect for what patient had to say.’ While deployed as a retrospective cross-sectional survey, it is independent from patient care and could allow for benchmarking and quality improvement efforts.

Care coordination

Proposed quality measure: e ffective c are c oordination b etween c linicians and patients with c ancer i ncluding p rimary c are p hysicians and p athologists to e nsure t imely d elivery of t reatment

Expert panelists identified ‘Effective Care Coordination Between Clinicians and Cancer Patients Including Primary Care Physicians and Pathologists’ as an important measure to address gaps in care coordination between the primary cancer team and other healthcare providers sharing a mutual patient, as well as between the provider and the patient. Panelists emphasized the need for an ongoing exchange of information between clinicians (oncologists and subspecialists involved in managing patient-related toxicities) and assessing the coordination in educating primary care providers and patients on awareness for the risk of irAEs. Pathologists were also specifically identified as essential members in care coordination for patients considering immunotherapy, as a lack of coordination and miscommunication about tissue samples, biomarker testing, and other tests can negatively impact patients’ treatment plans.37 40–42

Communication between healthcare providers should be streamlined and documented in patient records and electronic medical record tools to acknowledge the exchange of information and plan of care in the event of an AE. Panelists emphasized the need to determine how measures could be implemented and documented in a community hospital compared with larger academic institutions, as community or rural settings may be more prone to fragmentation. Optimal care requires close integration among primary care providers, surgeons, medical oncologists, subspecialists engaged in managing potential AEs, surgical and molecular pathologists, radiologists’ teams, and other members of the cancer care team to interact as part of a multidisciplinary approach to deliver care to the whole patient, especially when immunotherapy is being considered.43 44

Effective prevention and treatment

Proposed quality measures: (1) c oncordance with n ationally r ecognized c ancer i mmunotherapy g uidelines/ p articipation in a c ertificate p rogram; (2) b iomarker t esting and a ppropriate c ancer i mmunotherapy p rescribing

Panelists acknowledged challenges defining a measure concept to address the prioritized gap of prescribing appropriate and timely first-line, second-line, or subsequent/maintenance cancer immunotherapy. In line with CMS’ goals to shift toward cross-cutting quality measures, an ideal measure denominator would include all patients with cancer treated with immunotherapy. However, evidence and standard of care differs across tumor types and among different immunotherapy drug classes. Panelists recommended both broad and narrow quality measure development.

The broad measure concept, ‘Concordance with Nationally Recognized Cancer Immunotherapy Guidelines/Participation in a Certificate Program’, focuses on following nationally recognized cancer immunotherapy guidelines and could be applied across all types of cancer where immunotherapy is indicated. For example, a certificate program that recognizes providers and/or organizations with experience in immunotherapy administration could serve as a proxy for demonstrating competency, with institutions and payer organizations recognizing either this certification or a threshold of certificate holders in their provider settings. An MIPS improvement activity45 recognizing immunotherapy prescribing certification could also be developed as a surrogate to quality measurement. The CMMI OCM includes a similar requirement for participants and specifies that participating practices and providers provide ‘treatment with therapies consistent with nationally recognized clinical guidelines’.46 Some panelists viewed this concept as a ‘checkbox’ measure and indicated policymakers are moving away from unaudited attestation measures but others embraced this as more informative than current meaningful use requirements for providers to confirm in the medical record that national guidelines have been used in clinical decision-making. For example, panelists envisioned demonstration of individual provider certification or the number of certified providers within a healthcare delivery system as an easily reported measure. It will be important to establish whether certification is associated with improved patient outcomes.

The narrow measure, ‘Biomarker Testing and Appropriate Cancer Immunotherapy Prescribing’, focuses on biomarker testing for select populations to assess the timeliness of biomarker testing for patients and whether appropriate accompanying treatment was prescribed. Healthcare providers should be familiar with and adhere to existing practice guidelines regarding biomarker testing for optimal patient care. Biomarker testing that is not timely may make a difference in treatment decisions and/or patient outcomes. Appropriate treatment delivery could be delayed, or ineffective therapies could be prescribed, resulting in poor clinical outcomes and unnecessary healthcare costs.47 There is an existing evidence base and standard of care for established biomarkers, such as PD-L1 testing, which supports the case for measures focused on biomarker testing in patients with tumors such as non-small cell lung cancer, urothelial carcinoma, and head and neck cancers.42 Notably, studies have found undertesting for PD-L1 expression prior to immunotherapy prescription.48 This may be attributed to lack of tissue for staining, inappropriate tissue collection and/or preservation for biomarker testing, lack of concordance in regard to the PD-L1 testing platform based on the immunotherapeutic drug being prescribed, inconsistent thresholds used to determine PD-L1 positivity (tumor cell and/or immune cell), as well as heterogeneity among different tumor types. Appropriate utilization of other biomarkers for immuno-oncology therapies such as microsatellite instability, DNA mismatch repair deficiency, and implementation of next-generation sequencing for the identification of emerging biomarkers, including tumor mutation burden, should be considered. These are new challenges faced by the healthcare team that may contribute to the delay or lack of PD-L1 testing. Such measures would allow for nuanced performance benchmarking.