By Anna DeSalvo, MS, CGC, practice implementation principal, National Marrow Donor Program/Be The Match
Patient-reported outcomes (PROs) offer unique insights that complement traditional treatment efficacy endpoints, such as survival or disease relapse, and can facilitate better discussions between clinicians and patients. When PROs are incorporated into clinical trial protocols, sponsors can gain a better understanding of the treatment’s impact from the patient’s perspective. Additionally, better understanding patients’ experiences can enhance research questions and implementation of research results in the future.
PROs are “any report of the status of patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else,” according to the FDA.1 They are the most patient-centered measurement of the experience with disease and treatment because the information comes from the patient.
Potential PROs are wide ranging. Examples of measurements include quality of life (QOL), side effects from treatment like fatigue or pain, functional status, and financial status.
The field of hematopoietic cell transplant (HCT) provides case examples that show the information gained is clinically meaningful and centralized PRO data collection is feasible.
Pretreatment PROs Can Be A Predictor Of Post-Treatment Outcomes
The first case example comes from a multi-center biologic assignment trial conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). The primary goal of BMT CTN 1102 was to better define the benefit of reduced-intensity conditioning (RIC) allogeneic HCT over non-HCT in patients aged 50 to 75 with higher risk de novo myelodysplastic syndrome (MDS).2 As a secondary outcome, the researchers wanted to understand the impact of HCT versus non-HCT therapy on patient QOL via PROs.3
This was critical because concerns about increased toxicity for older patients with MDS historically limited the use of allogeneic HCT in this population. That is a problem for two reasons. First, allogeneic HCT is currently the only available curative therapy for MDS. Second, and just as important, MDS is not common in people under age 50 and is most common in people in their 70s.4
The primary analysis demonstrated a significant survival benefit for those patients who had allogeneic HCT. The secondary analysis on QOL compared PRO scores between study arms.
Patients who spoke English or Spanish completed PRO assessments that consisted of the Functional Assessment of Cancer Therapy General scale (FACT-G) and the Physical Component Score (PCS), which assessed perceived physical functionality, bodily pain, and general health, and a Mental Health Component Score (MCS), which examined mental health, social function, and vitality. Patients completed the assessments at enrollment, as well as at six, 12, 18, 24, and 36 months post-enrollment.
The researchers found that patients who underwent HCT and those who did not had similar PRO trajectories: decreasing or stable from baseline to six months with improvements thereafter. They also found that the baseline PRO scores were a consistent predictor of survival outcomes and subsequent QOL outcomes, such that patients with higher QOL at baseline were more likely to have higher QOL at subsequent timepoints compared to patients with lower baseline QOL.
The analysis of PRO outcomes led them to conclude that the survival advantage for patients who underwent allogeneic HCT did not come at the cost of a worse QOL. Physicians and older patients can use this information when making treatment decisions.3
The second case example comes from another trial, BMT CTN 1101, designed to evaluate the impact of donor source on post-HCT QOL. The BMT CTN 1101 compared outcomes for patients who received haploidentical (haplo) HCT to those who received double umbilical cord blood (UCB) HCT. The patients completed QOL assessments pre-transplant, 12 months post-transplant, and 24 months post-transplant.
The analysis of PROs found no significant difference between patients who received haplo HCT and those who received UCB HCT. In this case, there were no significant associations between pre-HCT QOL and survival. However, as with the analysis of the BMT CTN 1102 study, pre-HCT QOL scores were a significant predictor of post-HCT QOL scores.
This information can be valuable to physicians and patients making treatment decisions. Because QOL does not seem to be impacted by the choice of a haplo versus double UCB HCT, it suggests either may be a suitable option.5
Both studies indicate that pre-HCT QOL is a significant indicator of post-HCT QOL. This confirms the importance of transplant centers including QOL as part of pre-HCT performance assessments.
Systematic, Centralized PRO Collection Is Feasible And Useful
While HCT researchers and clinicians recognized the value of PROs, HCT outcomes registries did not have a systematic, centralized process to collect PRO data along with clinical data.
CIBMTR (Center for International Blood and Marrow Transplant Research) has been collecting HCT outcomes data from patients worldwide for more than 40 years. That has resulted in a research database that contains information from more than 630,000 patients who have received HCT and other cell therapies.
CIBMTR researchers sought to understand the feasibility of prospectively collecting PROs at multiple time points from patients at transplant centers that report outcomes data to CIBMTR. Secondarily, they aimed to correlate these data to the clinical and demographic data in the CIBMTR research database.
First, the researchers used a hybrid model in which transplant centers obtained patient consent and administered the pre-HCT PRO measures locally; CIBMTR centrally collected PRO data at day 100, six months, and 12 months post-HCT. With high retention rates and participant satisfaction, the researchers concluded centralized PRO collection is feasible.
In addition, they found pre-HCT PRO scores were significantly associated with overall survival and post-HCT self-reported health related QOL and may have a better predictive value for mortality than clinical, demographic, and transplant factors collected traditionally.6
Today, CIBMTR has an electronic PRO (ePRO) data collection system and centralized protocol in place so that all steps of the research are completed within CIBTMR. CIBMTR collects a routine set of PRO data under the protocol and these data are added to the CIBMTR Observational Database.
These data supplement traditional outcomes, such as survival or disease relapse, and can be used by researchers to:
- understand how patients’ symptoms and functioning change over time;
- evaluate which symptoms and functioning may affect outcomes for patients who have HCT or another cell therapy; and
- assess long-term patient outcomes after treatment.7
In addition, CIBMTR supports clinical trial investigators with PRO data collection. This includes supporting the clinical trial protocol team in selecting PRO measures to meet the study’s aims. The team assists with development of PRO-related sections of the study protocol, consent form, and study plans.
Following activation of the clinical trial, the CIBMTR Survey Research Group centrally collects PRO data and tracks and communicates PRO submission compliance.8
Ensuring Representation In PRO Collection Is Critical
As clinical trial sponsors incorporate PRO collection into their protocols, they must also ensure diverse participation in their clinical trials. Without it, PRO findings are not generalizable to the full population of patients who will be treated.9
The secondary analysis of QOL for the BMT CTN 1102 study of older patients with MDS is a case in point. The study authors specifically state that the study was no exception to the historical lack of underrepresented participants and, therefore, the QOL findings were limited to mostly non-Hispanic white patients.2
To help increase clinical trial diversity and ensure PRO findings are generalizable to all, clinical trial sponsors can take steps such as:
- Include a diversity recruitment section in the clinical trial accrual plan and monitor enrollment.
- Start with eligibility criteria that are as broad as possible.
- Instill patient trust by collaborating with advocacy organizations and community groups.
- Help patients understand clinical trials and navigate the process.
PROs offer unique insights and clinically relevant information. By routinely adding PRO collection to clinical trials, sponsors can support informed decision making between patients and their healthcare providers.
- U.S. Food & Drug Administration. Guidance Document: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. Accessed May 12, 2023. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-reported-outcome-measures-use-medical-product-development-support-labeling-claims.
- Nakamura R, Saber W, Martens MJ, et al. Biologic assignment trial of reduced-intensity hematopoietic cell transplantation based on donor availability in patients 50-75 years of age with advanced myelodysplastic syndrome. J Clin Oncol. 2021;39(30):3328-3339. doi: 10.1200/JCO.20.03380
- Cusatis R, Martens MJ, Nakamura R, et al. Health-related quality of life in reduced-intensity hematopoietic cell transplantation based on donor availability in patients aged 50–75 with advanced myelodysplastic syndrome: BMT CTN 1102. Am J Hematol. 2023;98(2):229-250. doi: 10.1002/ajh.26768
- UpToDate. Clinical manifestations, diagnosis, and classification of myelodysplastic syndromes (MDS). Accessed May 12, 2023. https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-classification-of-myelodysplastic-syndromes-mds.
- El Jurdi N, Martens M, Brunstein CG, et al. Quality of life in patients undergoing double umbilical cord blood vs. haploidentical marrow transplantation: A QOL analysis report of BMT CTN 1101. Blood. 2022;140(S1):10545–10546. doi: 10.1182/blood-2022-158828
- Shaw BE, Brazauskas R, Millard HR, et al. Centralized patient-reported outcome data collection in transplantation is feasible and clinically meaningful. Cancer. 2017;123(23):4687-4700. doi: 10.1002/cncr.30936
- CIBMTR. PRO Data Collection Protocol. Accessed May 5, 2023. https://cibmtr.org/CIBMTR/Data-Operations/Protocols-Consent-Forms/PRO-Data-Collection-Protocol.
- CIBMTR. Patient-Reported Outcomes (PRO) Data Collection. Accessed May 5, 2023. https://cibmtr.org/CIBMTR/Studies/Research-Programs/Patient-Reported-Outcomes-PRO-Data-Collection.
- Calvert MJ, Cruz Rivera S, Retzer A, et al. Patient reported outcome assessment must be inclusive and equitable. Nat Med. 2022;28:1120-1124. doi: 10.1038/s41591-022-01781-8
About The Author:
Anna DeSalvo is a practice implementation principal at the National Marrow Donor Program (NMDP)/Be The Match. In this role, she helps translate research findings into meaningful programs and standardized practice to provide the best care and outcomes for patients. Previously, she worked with the clinical trials search and support team within NMDP/Be The Match. Prior to joining NMDP/Be The Match, DeSalvo worked as a genetic counselor in multiple clinical settings including oncology and clinical genomics. She graduated from the Icahn School of Medicine at Mount Sinai genetic counseling program in 2016 and received a certificate in implementation science from the University of California San Francisco.