Patient Quality of Life Endpoints in Oncology Trials, Part II

Today we continue our discussion of symptom management and quality of life outcomes in cancer clinical trials with Bryce B. Reeve, PhD, associate professor in the department of health policy and management and a member of the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill and Carol M. Moinpour, PhD, full member of the Fred Hutchinson Cancer Research Center, Public Health Sciences Division.

-Interviewed by Anna Azvolinsky, PhD

Cancer Network: Professor Moinpour, you mentioned that quality of life endpoints have now been incorporated into SWOG trials. What are the main challenges in incorporating these quality of life or symptom measurement data into clinical trials from both of your experiences?

[[{"type":"media","view_mode":"media_crop","fid":"18093","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_3097548391848","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"1226","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":"Carol M. Moinpour, PhD","typeof":"foaf:Image"}}]]Prof. Moinpour: With regard to my work in SWOG, one of the questions I always struggle with and solicit a lot of clinical input from physicians and nurses involved in trials, is identifying the appropriate time points for assessing quality of life in the trial, so that you are evaluating both treatment arms fairly, that you are minimizing missing data, and that you are collecting data at clinically meaningful times.

I often ask the clinicians when they would expect that at least one of these treatments would be having some effect on patient quality of life, so that we would be sure to assess at that time point. This is different in every trial, so there is not a template, except that we would like to measure quality of life at least three times in SWOG trials. Time points you select for quality of life outcomes are completely tailored with respect to the nature of the disease and the treatment being used, as well as the clinical questions.

We also don’t like to schedule quality of life assessments that are not the same as regularly scheduled clinic visits, as this is a burden for patients and would contribute to missing data. If we ever get around to having really good infrastructure for electronic data capture of quality of life data, then that may not have to be the case, as the data could be captured electronically at any time point.

Cancer Network: Professor Reeve, any other challenges to highlight?

[[{"type":"media","view_mode":"media_crop","fid":"18096","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_8841489663545","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"1227","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":"Bryce B. Reeve, PhD","typeof":"foaf:Image"}}]]Prof. Reeve: I agree wholeheartedly with Dr. Moinpour’s recommendation that we need to have a thoughtful approach to when the quality of life assessment is integrated within a longitudinal study. To have just a baseline quality of life assessment and one at the end of the study is a mistake seen in past trials. What is missing is the rich data in between those two time points, where you want to describe how the treatment or intervention is impacting the patient. There is a need for accurate assessment throughout the trial, but yet not by overburdening the patient with daily questionnaires.

I think other issues that are important in thinking about integrating patient-reported outcomes in clinical trials is really the upfront decision, which is, what quality of life endpoints do you want to include in your trial? I don’t think that a lot of investigators think of these things as much as they should. Some make the mistake of just grabbing any quality of life questionnaire out there and throwing it into the trial, and they have no idea how their endpoints are impacted or what to expect as a result of the trial.

So, what Dr. Moinpour and I and others who work on patient-reported outcomes research believe is that there needs to be a thoughtful discussion about what are the most clinically relevant and patient-relevant endpoints to include in the clinical trial. What is the underlying mechanism of the cancer or the intervention itself that will impact those endpoints? There needs to be a lot more meaningful upfront discussion about what those endpoints are. That discussion should also include patient advocates and patients themselves who are key stakeholders in this process. Once the endpoints are identified, then the next challenge is how to select a proper endpoint with the quality of life instrument itself.

Again, there is a whole menu of quality of life research questionnaires, and what Dr. Moinpour and I have been trying to do is to guide researchers on how to collect the most valid and reliable measure of important patient quality of life factors in the clinical trial. The next step is then to integrate the quality of life endpoint at meaningful time points in the trial, as Dr. Moinpour mentioned. There also needs to be an upfront plan for the analyses and reporting of the quality of life findings. We would suggest that the reporting of the quality of life endpoints be at the same time as the reporting of the findings on the primary endpoint. Finally, what we also need is an effective dissemination plan, how to disseminate this quality of life information to a wide audience of key stakeholders to help inform decision-making in the clinical practice setting.

Prof. Moinpour: I would like to add another issue to this discussion, and that is the importance of how to minimize missing data when planning a trial. Missing data are common in advanced-stage disease because of the situation patients are in with expected shorter survival. But there are a lot of causes of missing data that are not related to patients’ health status. So what you want to do is minimize those missing data by educating and informing the institution staff about the importance of the measures. It is really critical that if there is a quality of life outcome in a trial, that it be included in every section of the protocol, that it is included in the objectives, in the introduction, and background of the basis of the trial, and that it is part of the eligibility requirements-in all of the sections. This is critical because it signifies that the quality of life outcomes are just as important as the other outcomes in the trial.

Cancer Network: In general, are these types of patient-centered studies generally funded by academia or are there also pharmaceutical industry–funded studies that are now incorporating such measurements-quality of life and symptom measurements? Professor Moinpour, let’s start with you.

Prof. Moinpour: The main way in the cooperative group setting that these trials are funded is through the treatment and the Community Clinical Oncology Program (CCOP) grants to the cooperative groups, which support the cancer control research. But because the quality of life data are resource-intensive, if a pharmaceutical company is supporting the trial in terms of providing the drug, or maybe two companies are providing two different drugs that are being used in the trial, sometimes they also support other studies, such as biomarker studies or quality of life studies. This does not mean that they have anything to do with the analysis or any decisions about what gets published and what does not. When their support is obtained, they are able to see abstracts and papers prior to submission, and often some will have helpful comments for those papers or abstracts, but they cannot keep something from being published. So, the statistical center of the cooperative group has total control over the data. Often pharmaceutical funding for collection of quality of life data supports the institutions for their time in collecting the long-term, follow-up data on quality of life.

Another point is that the pharmaceutical industry itself, as Bryce mentioned earlier,  has done a number of trials with quality of life outcomes, and more recently, they are totally guided by the FDA guidance for quality of life outcomes for drug labeling claims. One of the issues that we have run into in doing some of these studies is that if there is no opportunity for pharmaceutical funding, investigators are asked to get outside funding through grants. This is difficult because it takes a long time to receive grant funding, and this can hold up the conduct of the trial. This is usually not a productive way to fund quality of life studies.

Cancer Network: Professor Reeve, do you have anything to add?

Prof. Reeve: If we expand beyond clinical trials to observational studies or comparative effectiveness research (Ahmed et al, 2012), there are other organizations that certainly support this type of research. The American Cancer Society, for one, and other organizations have supported cancer research and studies that include quality of life endpoints and patient-centric endpoints. More recently, the Affordable Care Act formed the independent organization, the Patient-Centered Outcomes Research Institute or PCORI. This organization supports patient-centered outcomes research (PCOR) (Reeve et al, 2013).

As we move from clinical trials to the comparative effectiveness research arena, PCOR looks at how these interventions, which in the clinical trial setting looked at these quality of life endpoints in a more homogenous population, now impact a more diverse population, in terms of race, ethnicity, those with multiple comorbidities, and different age groups. I think there is a broad set of industry, government, and nonprofit organizations that have invested quite a bit into looking at the impact of these interventions in terms of quality of life.

Cancer Network: Thank you so much to both of you for joining us today.

Prof. Reeve: Thank you very much, it has been our pleasure.

Prof. Moinpour: Thank you!

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