FOCUS on strategy.

The progress made in prevention, early diagnosis, and treatment of all forms of cancer has led to substantial improvements in survival during the last quarter century. From 1999 to 2015, cancer death rates have declined per year by an average of 1.8% for men, 1.4% for women, and 1.5% for children in the United States.¹ While this progress is remarkable, many of the novel health technologies that have led to these declines have come at a steep financial price; in less than a year, the United States will spend $158 billion on cancer care.^2,3 This reality has spurred innovative thinking in how we evaluate novel health technologies versus existing standards of care from a patient, payer, and societal perspective. Since the World Health Organization (WHO) promulgated its definition of health in 1947 as “… not merely the absence of disease [but] also physical, mental, and social welfare,” psychosocial models of health (as opposed to biomedical models) have been used to determine whether a novel health technology is cost-effective.⁴ To be consistent with the WHO’s definition of health, a cost-effectiveness analysis of a health technology requires enumeration of the real or perceived benefits and costs to the patient as reported by the patient.⁵

These real or perceived patient-centered benefits and costs can be measured through patient-reported outcomes (PROs) instruments.⁶ For oncology drugs, the patient’s perspective is critical to the value of a health technology: the real-world cancer patient’s perspective of value is driven not only by the potential of longer life but also by the burden of the disease and its treatment.

While the United States does not mandate any form of cost-effectiveness analysis (CEA) for determining if a therapy will be covered by an insurer, novel forms of reimbursement through value-based contracting (bundled payments, MACRA/MIPS) are more than ever being used to force the hand of the drug manufacturer to develop on the promise of value. Since the release of FDA guidance in 2009 on PRO data for labeling claims, an increasing number of oncology drugs have presented this data as part of their new drug applications.^7,8 In practice, PRO data used in CEA is collected in clinical trials using validated instruments. However, as clinical trials are controlled environments where patient populations are highly selective, they may not reflect the demographic, clinical, or lived experience of real-world patients.⁹ As such, PRO data collected in trials can only provide insights into highly selected populations and settings of care, and may not be contemporaneous with the existing standard of care (given the pace of development). Real-world PRO evidence is needed to augment the findings from clinical trials.

Given the renewed importance that patients, providers, payers, and policymakers are placing on outcomes beyond survival, the study of PROs in oncology continues to expand. However, to overcome institutional operational inertia in healthcare, real-world PRO research poses unique challenges that require novel solutions. The purpose of this article is to outline those challenges by discussing the following topics:

1. Where and in what format do PRO data currently exist?
2. How are providers engaged in PRO research and what role do they need to play?
3. How can we improve the scientific rigor of real-world PRO research? 

Therefore, currently, the most scientifically rigorous, but also most intrusive and costly way to collect robust PRO data, is through a prospective research study. The most commonly employed method is to create a patient registry, but practical limitations have provided challenges that have slowed their widespread use.¹⁶ The primary limitations of the registry approach are issues with compliance, difficulties engaging patients, and a lack of patient follow-up on surveys. Prospective PRO research studies are also problematic from a time and resource perspective. Patients are invited to participate in the research, must consent to participate in the research, and complete their assessments as specified in the research study protocol. Gaining buy-in from both patients and providers for participation in this type of research is challenging. Fundamentally, both groups may question the value in collecting these data unless there is an explicit intent in the studies to conduct true comparative effectiveness research between alternative treatment strategies.

Additionally, within the last 10 years, providers have faced a new daunting reality of less hours and more work when it comes to providing patient-centered medical care. Providers face numerous new requirements when treating patients which has led to physician burnout. Participation by providers, however, is essential to the rigorous collection of PRO data. Providers’ participation may be needed to explain the importance of the data to their treatment of the patient. Additionally, providers may be necessary to enhance the raw data collected from the patient, with additional clinical insights that may not be available in the structured data element of an EMR. Marrying robust clinical data with PRO data often requires a patient-provider dyad with both parties contributing time and energy to the effort.

In multiple prospective studies, integrating ePROs into routine cancer care has improved patient–clinician communication, patient satisfaction, symptom management and control, and quality of life.¹⁷ In general, when patients receiving active cancer treatment or following their cancer surgery are offered an electronic system to self-report symptoms, 80% to 85% will regularly provide this information, even over long periods of time, and even when elderly, ill, or have end-stage disease.¹⁸ Nurses find symptom email alerts to be useful and actionable. Recent data have found reductions in emergency room visits, longer tolerability of chemotherapy, and improved survival.¹⁷ This evidence of benefits has led to a growing interest in this approach.

To help overcome the challenges discussed and foster an environment for collecting real-world PRO data, Cardinal Health is developing a Practice Research Network (PRN). The PRN will consist of practices that have been assessed by Cardinal Health to determine their capability to participate in potential PRO research studies sponsored by Cardinal Health pharmaceutical manufacturer clients. Practices in the PRN that participate in a sponsored research study may be required to identify, recruit, and enroll the patients in the study. The practices may also be asked to complete an electronic case report form (eCRF) to define the clinical characteristics, treatment patterns, and disease-related outcomes. Patients may be able to complete an ePRO instrument via a web-based portal, as practices in the PRN will have no infrastructure requirements that will need to be installed at their locations. Through a unique patient key, the clinical and PRO data could be linked, and privacy protections maintained. 

Currently, the main barrier to widespread adoption of PROs in routine oncology care is largely logistical and includes technology configuration, integration into existing workflow, and engagement of patients and clinicians. Buy-in by both patients and providers is needed and critical to the success of any PRO research study.

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