Symptom Research
Peter M. Grace, Ph.D.
Department Chair Ad Interim
Areas of Research
- Pain
- Artificial Intelligence
- Cancer Treatment-Induced Neurotoxicities
MD Anderson's Department of Symptom Research is at the forefront of discovering new ways of identifying the symptoms and neurotoxicities associated with cancer and its treatment, the mechanisms underlying such symptoms and toxicities, and interventions that might reduce symptom severity or prevent symptom occurrence altogether. The department also advocates for policy change, awareness on the part of funding agencies, and broad inclusion of patient report in clinical studies, especially drug development trials. Because symptoms are subjective experiences, we believe that only the patient can truly know the severity, temporal pattern, quality, location and impact on activities and daily life that symptoms have — and that the patient’s voice must therefore be heard.
We Are Hiring!
Assistant professor research faculty positions contribute to the efforts of the Department of Symptom Research.
Open Faculty Positions
We are seeking candidates for Assistant Professor research faculty appointments. General information about research faculty positions at MD Anderson is available here.
If you are interested in joining our team in the Department of Symptom Research, please send your CV to Carrie L Howard, Department Administrator. Carrie can answer any questions you may have.
Our Research Goals
The overarching goals of the Department of Symptom Research are to reduce the severity of the symptoms and toxicities of cancer and its treatment and to lessen their effect on daily activities and quality of life.
August Concert in Zayed
Co-sponsored by the Symptom Research and Neurosurgery departments, the Music in Medicine program presents Mark Kaplan (violin), David Kaplan (piano), and Mei Rui (piano) playing The Great Romantics: Brahms and Schumann sonatas. Join us Wednesday, Aug 20, at noon in the Zayed Building 2nd floor lobby.
Zoom link at the Music in Medicine website:Symptom Assessment Questionnaires
The Symptom Research department designs and licenses patient-reported outcomes (PRO)-based assessment questionnaires to measure the symptoms patients are experiencing, the degree to which these symptoms interfere with the patient's daily functioning, and how they affect patient quality of life.
Explore the Symptom Assessment Questionnaires catalog.
Frequently Asked Questions
Symptom Assessment and Patient Report
"Fit-for-purpose" patient-reported outcome (PRO) measures are an invaluable resource for helping us to better understand how patients are actually being affected by new therapies. The US Food and Drug Administration considers a PRO tool to be “fit-for-purpose” for regulatory decision-making if the tool’s level of validation is sufficient to support its context of use.
This is especially important in the developmental pathway for new drugs, given that these PRO measures will enhance information about treatment tolerability and potential symptom-reduction benefit earlier in the drug-development process.
Read below about issues related to PROs in research and clinical practice.
What is a Symptom?
Webster's Third New International Dictionary defines a symptom as “the subjective evidence of disease or physical disturbance observed by a patient.” Implicit in this definition is that symptoms — for example, fatigue, pain, nausea — are observations of the patient, the person experiencing the evidence of disease or physical disturbance. Thus, in contrast to objective “signs” of disease (such as fever or high blood pressure), symptoms can truly be known only through patient report.
Symptoms add to the burden of having a chronic disease such as cancer, and they affect virtually all aspects of life. Symptoms interfere with a person's mood, level of activity and ability to relate to others. Moreover, symptoms rarely occur in isolation; rather, ample evidence indicates that symptoms frequently present in clusters. Within clusters, symptoms do not necessarily increase or decrease in tandem.
The concept of symptom burden includes the severity of these symptoms and the degree to which they interfere with daily living.
How Can We Assess Symptoms If They Are Subjective?
Symptoms can be classified according to their severity and perceived impact on function. These effects are best understood through self-report from patients across specific stages of specific types of cancer. Such patient-reported outcomes (PROs) have been recognized by the U.S. Food and Drug Administration as legitimate primary outcome variables for clinical trials.
The Department of Symptom Research designs general and fit-for-purpose PRO-based assessment tools for measuring the symptoms experienced by cancer patients. Routine and repeated use of such tools allows clinicians and researchers to determine symptom severity and how symptoms are affecting patient functioning and quality of life.
The overall design of our symptom assessment questionnaires (simple stem symptom items — e.g., your pain at its worst — and the 0–10 numeric rating scales) allow us to take advantage of technological advances in symptom reporting and communication of information from patients to health care professionals, particularly electronic links that make use of the Internet, smart phone apps and tablet PCs, and computer-telephone based interactive voice response (IVR) systems.
Visit our Symptom Assessment Tools page to view our wide-ranging PRO tool collection, all of which are available for licensing.
What is a Cutpoint?
A cutpoint is a number on a numerical rating scale that divides a continuous measure into discrete categories, such as mild, moderate, and severe. This kind of categorization aims to better inform treatment decision making for clinicians, facilitate the interpretation of study outcomes, and aid in the development of policy or clinical practice guidelines.
How Are Cutpoints Determined?
To determine cutpoints on the 0‒10 numerical rating scale, such as that used in the MD Anderson Symptom Inventory (MDASI), the Brief Pain Inventory (BPI), and the Brief Fatigue Inventory (BFI), Serlin et al. (1995) correlated pain intensity to the level of interference of the pain with the daily functioning of patients with cancer pain, by estimating how much of the variance in pain-related functional impairment could be explained by different possible pain intensity classifications. This approach has been repeated for other assessment tools designed for use with cancer patients, i.e., fatigue (Wang et al., 2012) and pain interference (Shi et al., 2017).
References
Serlin RC, Mendoza TR, Nakamura Y, Edwards KR, Cleeland CS. When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function. Pain 61(2): 277-84, 1995.
Shi Q, Mendoza TR, Dueck AC, Ma H, Zhang J, Qian Y, Bhowmik D, Cleeland CS. Determination of mild, moderate, and severe pain interference in patients with cancer. Pain 158(6):1108-12, 2017.
Wang XS, Zhao F, Fisch MJ, O'Mara AM, Cella D, Mendoza TR, Cleeland CS. Prevalence and characteristics of moderate to severe fatigue: a multicenter study in cancer patients and survivors. Cancer 120(3): 425-32, 2014.
When Are Symptoms Treatment-Related versus Disease-Related?
Symptoms can be produced by the disease itself or by the prescribed treatment, in which case they are often referred to as "side effects" or "toxicities." Symptoms can also arise from comorbid medical conditions or acute injuries. Whereas many cancer-related symptoms are the result of disease, it is increasingly recognized that neuropathy, fatigue, sleep disturbance, cognitive dysfunction, and affective symptoms can also be caused by cancer treatment.
It is frequently difficult for patients (and clinicians) to accurately ascertain the underlying basis of symptoms. The process of attribution involves making a judgment about the cause of toxicities that occur during the conduct of a clinical trial, and the degree to which these toxicities are due to the treatment under study or to a change in disease status or a comorbidity.
The Departments of Symptom Research and Investigational Therapeutics hosted a 1-day workshop on methods of attributing adverse events during a cancer clinical trial. The workshop was co-hosted by the Friends of Cancer Research and the Health and Environmental Sciences Institute and was attended by academic researchers, pharmaceutical industry clinical trial sponsors and investigators, the US Food and Drug Administration, European regulatory agencies, the National Cancer Institute, and contract research organizations.
The current practice of attribution was reviewed, and concerns were raised about the variability of attribution judgments, the need for early identification of toxicities from new agents, and the utility of attribution in the drug-approval process.
There was consensus that the current practice in attribution has challenges that may lead to misjudgments about drug safety. Overestimation of drug toxicity may lead to termination of a drug during its development or a decision about the maximum tolerated dose that may be below the level of the drug’s potential benefit. Conversely, underestimation may mask toxicities that will only become apparent after drug approval.
The recommendations of the workshop appear in a white paper suggesting changes in the attribution process that included training of principal investigators, revising the categories of attribution, and enhanced sharing of toxicity concerns during multisite, early-phase studies.
Funding for the workshop was provided by the MD Anderson Development Fund, the C. Stratton Hill Foundation, the MD Anderson Department of Investigational Cancer Therapeutics, AstraZeneca, and Genentech.
References
George GC, et al. Improving attribution of adverse events in oncology clinical trials. Cancer Treat Rev. 2019:76:33-40. doi: 10.1016/j.ctrv.2019.04.004. Epub 2019 Apr 25.
Cleeland CS. Symptom burden: multiple symptoms and their impact as patient-reported outcomes. J Natl Cancer Inst Monogr. 2007:(37):16-21. doi: 10.1093/jncimonographs/lgm005.
Cleeland CS, et al. Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? Cancer. 2003;97(11):2919-25. doi: 10.1002/cncr.11382.
Can Patient-Reported Outcomes Reflect Treatment Tolerability?
Assessing tolerability is a crucial aspect of cancer therapy development, as tolerability affects the patient's ability to continue treatment at the recommended dose. Although safety is assessed by the clinician, the patient’s voice can provide vital information about how tolerable the therapy is (or isn’t). Patient-reported outcomes (PROs) can be assessed by using validated, psychometrically sound questionnaires that elicit the patient's symptom experience.
Given the growing variety of new therapeutic agents and their wide range of mechanisms of action, the issue of treatment tolerability in clinical trials is becoming more urgent — and more complex.
A number of important conceptual challenges exist in the development and use of PRO assessment tools. These include how to track and characterize the trajectory of adverse events, especially low-grade events over the longer term. Other issues are how and whether to assess the overall burden of symptomatic side effects and whether a summary score can give appropriate sensitivity to specific side effects. Different dimensions to symptom burden can be considered as well, such as the interference items used in the MDASI assessment. Further study is needed in this area.
Sustained international effort is ongoing toward including PRO assessments of adverse events across all stages of the drug development process, from trial design to clinical trials to labeling claims. This will help with effective assessments of tolerability and safety at all stages of drug development.
There is significant value in better forms of communicating a drug’s side-effect profile to patients, clinicians, and regulators. Collecting and analyzing PROs are vital components of this communication.
Is Routine Symptom Monitoring Feasible?
At ASCO 2017, Ethan M. Basch, MD, MSc, FASCO, of The University of North Carolina at Chapel Hill, presented data on the use of a web-based system that allowed patients to report symptoms to their clinicians, prompting them to intervene earlier.
“Although symptom management is a cornerstone of high-quality cancer care, research has shown that doctors miss up to half of patients’ symptoms during cancer treatment,” explained Dr. Basch.
In the study, even among the elderly, patients self-reported 73% of the time when prompted to do so, and nurses acted upon 77% of the alerts they received. Interventions included referrals to emergency services, dose modifications, and counseling. Patients in the self-reporting arm experienced quality-of-life benefits and a median overall survival of 5 months longer, compared with patients in the standard-of-care arm.
Dr. Basch proposed that proactive symptom monitoring would prompt earlier intervention, help patients remain functional, and lead to better control of chemotherapy side effects, enabling longer and more intensive treatment in which prescribed doses can be maintained.
New Standard of Care?
The significant impact of the study was that it led to calls for symptom monitoring of this kind to become the new standard of care.
As one discussant highlighted, this model offered similar, if not greater, benefits than many of the latest approved drugs while providing a cost-effective way to improve outcomes.
References
Basch EM. Overall survival results of a randomized trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. Plenary session, American Society of Clinical Oncology Annual Meeting, 2017. J Clin Oncol 2017:35(suppl); abstr LBA2. doi: 10.1200/JCO.2017.35.15_suppl.LBA2.
Cleeland CS, et al. Automated symptom alerts reduce postoperative symptom severity after cancer surgery: a randomized controlled clinical trial. J Clin Oncol. 2011;29(8):994-1000. doi: 10.1200/JCO.2010.29.8315.
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Have questions? Contact Carrie L. Howard to learn more about joining our team.