Future Research Needs for Hematopoietic Stem-cell Transplantation in the Pediatric Population: Future Research Needs Paper Number 10

Publisher Marketing: For many pediatric indications, the use of hematopoietic stem-cell transplantation (HSCT) is not supported by high-quality trial data. In the absence of these data, the comparative effectiveness and harms of HSCT for these indications is uncertain. The Blue Cross and Blue Shield Association Technology Evaluation Center (BCBSA TEC) Evidence-based Practice Center (EPC) submitted a draft Comparative Effectiveness Review (CER) on HSCT in the pediatric population to the Agency for Healthcare Research and Quality. The six Key Questions addressed by the review evaluated the comparative effectiveness and/or harms of HSCT and alternative therapies for pediatric patients with (1) malignant solid tumors, (2) inherited metabolic diseases, and (3) autoimmune diseases. Overall there was a low to moderate strength of evidence for the various diseases and outcomes considered. Evidence consisted largely of case series and case reports. There was a preponderance of small uncontrolled studies, as is often the case in the study of rare diseases. Data synthesis was qualitative. Pooling was not attempted, as the data were not amenable to this approach. An effort was made to identify subgroups based on prognostic factors to see if these subgroups showed patterns of treatment success or failure. The objective of this Future Research Needs project was to systematically prioritize research gaps in the areas of HSCT for pediatric malignant solid tumors, inherited metabolic diseases, and autoimmune diseases, and to develop a list of research questions to address the prioritized gaps. In the first stage of this Future Research Needs report, we engaged a group of Key Informants to help develop the approach. (See "Engagement of Stakeholders, Researchers, and Funders" in the full report.) The draft CER that the Key Informants reviewed addressed over 40 diseases, with many diseases having more than one indication for transplant. After reviewing the draft CER, the Key Informants concluded that the Future Research Needs project should be focused on crosscutting evidence gaps that may be pertinent to all or some of these diseases. They stressed that the focus should be on the field as a whole, rather than specific diseases or groups of diseases. Based on these discussions, the crosscutting gaps identified in the draft CER on HSCT in the pediatric population that are pertinent to this project were identified. They are listed below. One crosscutting evidence gap may be pertinent to all or some of these diseases: What are the long-term consequences of HSCT, such as overall survival; functional measures; quality of life; and adverse effects, including infertility and secondary malignancies? In addition, two crosscutting issues were related to research methods and practice: What opportunities and obstacles exist for improving multicenter collaboration, increasing accrual of patients, and systematizing the reporting of outcomes and/or improving the ability to aggregate data collected at individual sites? Can a framework be developed to help decisionmakers incorporate contextual factors (the potential for new research, rarity of the disease, etc.) into the interpretation of the strength of the evidence? However, this is a methodological issue, which would require different expertise from that of the technical experts involved and is therefore outside the scope of this Future Research Needs project. After the completion of the draft CER and in preparation for the Future Research Needs project, a fourth issue emerged: Can the long-term adverse effects of HSCT be mitigated by changes in HSCT regimen and/or subsequent interventions? Comparison of specific regimens was outside the scope of the CER due to their evolving nature and difficulties in stratifying small populations by regimen. But it is well recognized that regimens vary in their potential for long-term adverse effects, so this was listed among the research gaps considered by the group.