FDA’s ODAC Weighs the Reliability and Validity of Using PROs in Pediatric Oncology

The FDA’s Oncologic Drugs Advisory Committee (ODAC) met to discuss the necessity, validity, and reliability of the use of patient-reported outcomes (PRO) measures linked to the Common Terminology Criteria for Adverse Events (CTCAE) in pediatric oncology .

Presentations were given from doctors treating childhood cancer at Children’s National, Duke Health, The Hospital for Sick Children, Comer Children’s, and the Children’s Oncology Group. These presentations addressed the rationale, clinical trial design, challenges and impact of the implementation of PROs in pediatric oncology.

The main topic of discussion was a new pediatric PRO-CTCAE developed by Childen’s National for use in children 7 to 17 years of age. The questionnaire is designed to assist with the most important issue of oncologists treating pediatric cancer patients; fatigue, pain, sadness, depression and worry.

Testing PRO-CTCAE in children

PRO-CTCAE for Children is designed to more accurately report treatment-related adverse reactions (AEs) and other conditions in children.

Pediatric Pro-CTCAE was evaluated in a study with 482 patients aged 7 to 18 years. Of the children, 41.5% were not non-Hispanic White people with newly diagnosed cancer and their caregivers. Each patient completed a survey 72 hours prior to the start of treatment and a follow-up questionnaire was completed 7 to 17 days later for chemotherapy and 4 or more weeks after the start of radiation. Psychometric analyzes examined the relationship of the 62 adverse events with the patient-reported outcome measurement information system, the Memorial Symptom Assessment Scale, the Lanksy Play-Performance Scale, and medication use. An additional separate test-retest study included 46 children

According to the results, the Pediatric PRO-CTCAE and Memorial Symptom Assessment Scale were highly correlated between the age groups at the second test, 7-12 years (range 0.62-0.80 years), 13-15 years (range 0.44- 0.94 years), and 16-18 years (range, 0.65-0.98 years); and over time. The system was also highly correlated with patient-reported outcomes Pediatric Measurement Information System at the second test, including at pain [CI], 0.64-0.76), fatigue severity (95% CI, 0.56-0.69), and depression severity (95% CI, 0.71-0.81). When it came to the Lansky-Performance Scale, children were differentiated by medication use

Pediatric PRO-CTCAE is a valid and reliable means of reported adverse events in children aged 7 to 18 years, according to the study. Future use of the system could help clinicians know how to respond to identified symptoms and improve CPG concordant care. In addition, since many childhood cancer patients have chronic conditions, gathering data on symptoms and side effects can now help address those conditions later.

The case for PROs from pediatric cancer patients

Because of the toxicity of treatments, 2 in 3 childhood cancer survivors will develop at least one chronic health condition, which can be either musculoskeletal problems or second cancers. In addition, nearly 60% of pediatric patients who survive cancer experience serious or life-threatening complications in adulthood.

The vast majority, 90%, of sick children do not report symptoms unless doctors directly ask about them. The most common side effects in children are fatigue, pain, sadness, depression and worry. However, children are not routinely asked about toxicities.

According to a presentation by Pamela S. Hinds, PhD, RN, FAAN of Children’s National Hospital and Bryce B. Reeve, PhD of the Duke Cancer Institute, health care providers must learn how to translate medical jargon into child- and adolescent-friendly terms. For example, if you are talking about stomach pain, call it ‘stomach pain’ or dysphagia as ‘difficulty swallowing’.

“I think this kind of information can be incredibly valuable, especially since I care for many patients with multiple recurrent cancers, and many of the interventions we are considering may have only a modest impact on event-free survival or relatively modest response. , but if I had data that patients taking the drug might feel better than patients not taking the drug, even if progression-free survival didn’t improve much, if patents felt better … then that could be helpful, ”said Steven DuBois, MD, MS, a pediatric hematology oncologist at Dana-Farber Cancer Institute.

PROs as a resource for pediatric oncology physicians

Just as PROs are used to support physicians’ treatment decision in adults with cancer, part of the ODAC meeting focused on how physicians will benefit from PROs questionnaires used in pediatric oncology.

Hospital for Sick Children presenters hypothesized that implementing PROs can help oncologists respond to adverse effects and improve care to a standard consistent with Clinical Practice Guidelines. Furthermore, it can aid in the detection of side effects and the design of clinical studies.

According to presenters, health care providers intervene for serious unpleasant side effects, such as pain 96% of the time and headache 89% of the time. However, feelings of fear or anxiety were addressed 56% of the time and disappointment or sadness were addressed 12% of the time.

‘I believe both [the] psychological and cognitive effects of our treatment are grossly underestimated because this tool can be very important in uncovering some of those questions we will never ask our patients, ”said Tobey J. MacDonald, a neuro-oncologist at the Winship Cancer Institute . “And this would be both in the acute setting and, of course, in the long run of what the impact is on those two very critical elements.”

References: Subcommittee on Pediatric Oncology of the Advisory Committee on Oncological Medicines (ODAC). FDA. May 11, 2021. Access May 11, 2021 Reeve BB, McFatrich M, Mack JW, et al. Validity and reliability of the pediatric patient-reported outcomes version of the Common Terminology Criteria for Adverse Events. J Natl Cancer Inst. 2020; 112 (11): 1143-1152. doi: 10.1093 / jnci / djaa016.

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