Patients and caregivers often complete patient-reported outcome (PRO) and observer reported outcome (ObsRO) assessments that support key efficacy endpoints in clinical trials. Patients and caregivers routinely receive instructions on what assessments to complete and how to use diaries or electronic diaries.
Just as critical, however, is providing advanced and customized training to patients and caregivers on meanings of key assessment terms and definitions, study objectives, what to expect in a clinical trial, and why compliance and participation is important.
Why provide advanced training to patients and caregivers?
One problem with PRO/ObsRO data is inconsistency in the way patients or caregivers conceptualize the symptoms being measured. Study participants can interpret PRO or ObsRO questions and responses in different ways, or even answer questions based on what they think the investigators are hoping to find. Additionally, patients commonly lack understanding of the measurement parameters and scoring anchors in study assessments.
Advanced, custom training for patients and caregivers improves the accuracy of clinical trial data by establishing standardized and unbiased subject ratings. Training focused on the PRO assessments and key definitions improves the consistency of subjective data collected from patients and caregivers. Training also focuses on the importance of accurate reporting and setting realistic expectations for the clinical trial, which are essential to mitigate placebo response.
Importantly, regulatory agencies state that training patients and caregivers is critical.1,2 FDA PRO guidance (2009) reports that
“Results obtained using a PRO instrument can vary according to the instructions given to patients or the training given to the interviewer or persons supervising PRO data collection during a clinical trial” and “The quality of a clinical trial can be optimized at the design stage by specifying in the protocol procedures to minimize inconsistencies in the trial conduct.”
The EMA echoes this recommendation, stating that patient/caregiver training is needed for data to be accurate and to be sure that the study participant is recording what they are intending to record. EMA also stresses that industry sponsors should have this training documented for their trials.2
When is advanced patient and caregiver training most useful?
Training is essential for PROs and ObsROs that contribute to a primary or key secondary endpoint in phase II & III trials, especially those intended to support a label claim. Patient and/or caregiver training is especially critical for the following indications and scenarios:
- Rare disease: As rare disease populations are limited, patients who are eligible for these trials are very difficult to recruit, so missing or inaccurate data from just a few patients can detrimentally impact a study’s statistical power.
- Gastrointestinal disease: Patients within this population tend to misunderstand common symptoms frequently asked on PROs such as nausea, bloating, constipation, and diarrhea, compromising data quality.3
- Pediatric patients: The pediatric population often requires observers or caregivers to report on the patient’s symptoms and behaviors. Caregivers of children are susceptible to many sources of bias such as high expectations of improvement, and strong desire to see improvement.
- Individuals with cognitive impairment: Caregivers or observers of cognitively impaired patients are often asked to report on cognitive function for which even highly-trained clinicians have difficulty in establishing agreement.
Does advanced PRO-specific training increase data accuracy?
ERT’s clinical research shows that PRO-specific training is an effective method to improve accuracy on common endpoint-related data captured in clinical trials. ERT administered an online survey in which 613 patients were asked to provide responses to commonly seen PRO questions from various therapeutic areas, including questions relating to pain severity, rescue laxatives, stool counts, bleeding events, and itch severity.
Patients provided responses to the questions both before and after a brief, written training consisting of 1-2 sentences. A 16% increase in mean response accuracy was found among all 5 questions evaluated by patients.4 This data highlights that even minimal PRO-directed training can significantly improve data accuracy. Further improvements are likely given a more thorough training (5-10 minutes) created in the context of a clinical trial.
What motivates patients to complete assessments?
In addition to increasing the accuracy of PRO data, patient and caregiver training can motivate patients to complete their assessments. Patients are commonly required to record symptoms in an at-home diary and may be required to complete their diary on a daily or weekly basis. Because they are doing these diaries without supervision from site staff, they are more likely to forget to complete their diary on time, resulting in missing data.
In effort to determine what may motivate study participants to complete their assessments, ERT surveyed over 700 participants asking “what is the number one motivator for completing questionnaires on a daily basis?” The overwhelming response is that training on the importance of their role in the study and learning about the importance of the questionnaires is the number one motivator. It is interesting to note that training is more important than monetary compensation or gamification of the assessments. (Figure 1)
Strategies for providing advanced patient / caregiver training
We recommend that training modules are available throughout the study to allow study participants to review the training at any time. The training would ideally include study specific assessments with key terms and definitions, knowledge checks, and comprehension quizzes with remediated scoring to ensure the study participant understands the material.
Ideally, the training should be interactive on the eCOA device that participants will be using to complete their assessments. Participants should complete the on-device training module and quiz before they are allowed to enter data to ensure that only properly trained participants are entering study data.
Kelly Dumais, PhD, is a Clinical Scientific Advisor at ERT.
- European Medicines Agency. GCP Inspectors Working Group (CGP IWG)Reflection Paper on expectations for electronic source data and data transcribed to electronic data collection tools in clinical trials; June 09, 2010.
- US Food and Drug Administration. Guidance for Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. Rockville, MD: U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research; 2009.
- US Food and Drug Administration. Ulcerative Colitis: Clinical Trial Endpoints Guidance for Industry: Food and Drug Administration, Center for Drug Evaluation and Research; 2016.
- Dias NR, Howley AR, Yamamoto R & Dallabrida SM. Training subjects on key concepts from patient-reported outcomes (PROs) improves understanding and data accuracy. Patient Relat Outcome Meas. 2019 Oct 21; 10: 315-319.