While the collection and reporting of patient-reported outcome data in oncology trials and care settings has yet to reach its full potential, it has made some progress in recent years.
Patient-reported outcomes (PROs) are defined as “any report of the status of a patient’s health condition that comes directly from the patient’s response, without interpretation of the patient’s response by a clinician or anyone else.”1 Uses of PRO data in health care range from the “micro” to the “macro.” At the micro level, PROs collected from individual patients can help providers make more informed patient-level treatment decisions, such as changing dosing for antidepressant medications based on depression severity score. At the macro level, aggregated PRO data collected from a large group of patients as part of a clinical trial may inform clinical guidelines or be used to guide health policy decisions, such as how pain ratings aggregated across large samples identify the need for improved pain management strategies.
Initiatives calling for increased inclusion of PROs as endpoints in oncology clinical trials, and as a standard assessment in the practice of clinical medicine, go back many years.2 However, while the collection and reporting of PRO data in oncology trials and care settings has made some progress in recent years, it has yet to reach its full potential. The primary focus in oncology treatment research and clinical care is tumor burden, with symptom burden receiving less attention. A renewed emphasis on the importance of PROs in oncology is steadily increasing, largely in response to trends in health care reimbursement. Migration from a fee-for-service system to a patient-centric, value-based system requires that patient assessments be included in determining when treatments are successful. Additionally, there have been compelling studies presented this year that demonstrate how systematic symptom monitoring as part of routine clinical care results in markedly improved outcomes.
PROS AND VALUE-BASED HEALTH CARE
The term “value-based care” covers a wide swath of ground but generally refers to a cost–benefit ratio, in which “benefit” includes a variety of treatment outcomes, and “cost” refers to the toxic and monetary consequences of treatment. Approaches to measuring treatment benefit vary significantly but usually cite the importance of the patient experience as an expected element in any value calculation. The health care field is still in an early “consensus-building phase,” with calls to standardize treatment outcomes measurement, routinely including PROs.3
An example of the current status of attempts to drive this process in oncology can be found in the American Society of Clinical Oncology (ASCO) Value Framework, an algorithm that calculates standard metrics and allows treatment options to be compared using a value-based perspective.4 Measures of clinical benefit, toxicity, and cost are included in this algorithm to deliver normalized metrics for treatment regimens being considered by patients and providers.
Toxicity assessments would ideally include PROs, but these need to be reported at higher rates in pivotal trials to warrant inclusion in the standard algorithm. Additionally, patient needs, goals, and preferences must be assessed to optimize treatment decisions.
After the Value Framework was published in 2015, ASCO invited feedback from a broad set of stakeholders within the cancer care community. In response to this feedback, ASCO has just published an updated version of their value framework that addresses many of the concerns and comments of the community.5 The revised model acknowledges that “a substantial number of respondents commented on the lack of inclusion of PROs in the value framework.”5
Yet, there is already an editorial response to the revised framework calling for even more ambitious measurement of PROs to reevaluate treatment utilities for patients over the course of treatment.6 These authors make the case that the net health benefit is dynamic across the course of treatment and that it changes as patients experience toxicity, financial barriers, or other factors that might affect the value of their treatment. These valid points highlight the complexity of designing a value-based approach to measuring treatment outcomes, as well as the need to include the patient experience as part of a coherent solution.
PRO COLLECTION IN ROUTINE CLINICAL CARE
The utility of routine inclusion of PRO data in oncology care requires empirical assessment. Basch et al7 published a pivotal paper this year demonstrating improved outcomes across multiple domains when PRO data were systematically collected and presented to the provider team. This randomized controlled trial was methodologically rigorous and deserves careful attention. A sample of 766 patients with advanced solid tumors was randomized to receive either usual care or routine PRO assessment. The PRO instrument evaluated 12 common symptoms of cancer or cancer treatment. Stratification for “computer-experienced” versus “computer-inexperienced” was included, with the computer-experienced cohort reporting symptoms from their homes using the internet between clinic visits. Both groups provided symptom reports during clinic visits. These data were presented to the health care team for review at the time of the patient’s visit. When symptom data were collected remotely, alerts were sent to nursing staff when scores increased by 2 or more points or exceeded an absolute threshold of grade 3 or higher. Nurses then triaged patients according to usual clinic practice, which consisted of telephone counseling about symptom management. Patients in the PRO cohort experienced significant benefits across a variety of endpoints, including a higher quality of life, decreased emergency room visits, decreased hospitalization rates, and increased 1-year survival. Patients in the PRO cohort received active chemotherapy treatment for an average of 2 months longer (6.3 vs 8.2 months, P = .002),7 presumably because it was possible to better manage toxicity when symptoms were routinely evaluated. Given that hospitalization is an important driver of cost in cancer care, techniques that reduce that cost while also improving outcomes are key to achieving success in a value-based care model.
Research to define the mechanisms underlying these improvements in outcomes with PRO assessment is still needed. One obvious hypothesis is that PRO data provide a novel source of information that makes it easier for the care team to manage toxicity, allowing for a more complete delivery of planned therapy. The additional 2 months of chemotherapy in the PRO cohort supports the interpretation that patients in this group were less likely to experience early treatment discontinuation. Although health care providers have historically evaluated symptoms of drug toxicity as part of the clinical encounter, studies have shown that clinician ratings of these symptoms significantly underestimate severity when compared to patient ratings.8,9 Patient ratings provide unique input to clinical decision-making that can translate to more time on therapy and better outcomes.
An additional finding of particular interest in the Basch et al study7 is that the subgroup of computer-inexperienced patients had larger effect sizes across all endpoints compared with the entire cohort.7 These patients only completed PRO assessments during their time in the clinic because they did not have access to the internet at home. This subgroup was older, mostly male, had less education, and higher likelihood of minority status compared to the overall sample (all at P < .001).7 One interpretation of the large effect size of routine PRO assessment in this subgroup is that these patients were less likely to volunteer clinically relevant information. Therefore, the PRO symptom assessment closed an important gap in the health care team’s knowledge of the patient’s symptom burden, facilitating better treatment decisions. This interpretation requires empirical verification, however. The effect seen in this subgroup also shows that remote monitoring is not required, as automated in-clinic PRO assessment delivered significant benefit.
Another recent study reports the results of using a web-based application to assess 12 common symptoms associated with treatment for lung cancer.10 Patients were randomized to an experimental condition or usual care. In the experimental group, symptom data were analyzed in concert with other clinical data, and alerts were sent to the oncologist if the automated algorithm identified patterns suggesting the patient would benefit from unscheduled medical intervention. One-year survival was significantly improved in the experimental condition compared with the group that received usual care (75% vs 49%; P = .0025).10 Furthermore, at time of relapse, 77% of the experimental group had good performance status, allowing them to receive a new treatment, versus 33% of patients in the usual care group with good performance status (P < .001).10 One proviso is that these data are only in abstract form, and a fuller report of the findings is needed.
In summary, there is growing evidence that routine assessment of the patient experience with validated scales leads to better treatment outcomes in cancer care. Improved outcomes that are achieved while also containing costs will be required as part of value-based care models. Inclusion of PRO measures when developing treatment plans is required to create the evidence needed for more value-based care strategies.
For other takes on this topic, read the Viewpoint, "The Limitations od Patient-Reported Outcome Measurement in Oncology" and Counterpoint, "The Pivot Toward Patient-Centeredness in Medicine and Oncology."
1. US Department of Health and Human Services. FDA Guidance for industry. Patient-reported outcome measures: Use in medical product development to support labeling claims. http://bit.ly/2bAZlSp. Published December 2009. Accessed August 16, 2016.
2. National Institutes of Health. Symptom Management in Cancer: Pain, Depression and Fatigue. http://bit.ly/2bJM9sW. Published July 15, 2016. Accessed August 16, 2016.
3. Porter ME, Larsson S, Lee TH. Standardizing patient outcomes measurement. N Engl J Med. 2016;374(6):504-506.
4. 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;33(23):2563-2577.
5. Schnipper LE, Davidson NE, Wollins DS, et al. Updating the American Society of Clinical Oncology Value Framework: Revisions and reflections in response to comments received. J Clin Oncol. 2016;34(24):2925-2934.
6. Given CW, Given BA, Bradley CJ, et al. Dynamic assessment of value during high-cost cancer treatment: A response to American Society of Clinical Oncology and European Society of Medical Oncology [Published online ahead of print August 16, 2016]. J Oncol Pract. 2016. doi: 10.1200/JOP.2016.012401.
7. Basch E, Deal AM, Kris MG, et al. Symptom monitoring with patient-reported outcomes during routine cancer treatment: a randomized controlled trial. J Clin Oncol. 2016;34(6):557-565.
8. Di Maio M, Gallo C, Leighl NB, et al. Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials. J Clin Oncol. 2015;33(8):910-915.
9. Atkinson TM, Ryan SJ, Bennett AV, et al. The association between clinician-based common terminology criteria for adverse events (CTCAE) and patient-reported outcomes (PRO): a systematic review. Support Care Cancer. 2016;24(8):3669-3676.
10. Denis F, Lethrosne C, Pourel N, et al. Overall survival in patients with lung cancer using a web-application-guided follow-up compared to standard modalities: Results of a phase III randomized trial. Abstract presented at: ASCO 2016 Annual Meeting; June 3-7, 2016: Chicago, Illinois. Presented June 6, 2016.