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Translation of Clinical Research into Practice: An Impact Assessment of the Results from the Blood and Marrow Transplant Clinical Trials Network Protocol 0201 on Unrelated Graft Source Utilization.

ABSTRACT: Barriers and facilitators to adoption of results of clinical trials are substantial and poorly understood. We sought to examine whether the results of the randomized, multicenter Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 study comparing peripheral blood (PB) with bone marrow (BM) stem cells for unrelated donor (URD) hematopoietic cell transplantation (HCT) changed practice from PB to BM graft utilization and explored factors that impact graft selection and translation of research results into practice. The difference between use of URD BM and PB in the 2 years before and after publication of results in 2012 was examined using observational data collected by the Center for Blood and Marrow Transplant Research. A web-based survey of transplant physicians was conducted to understand the change in physician-reported personal and center preferred URD graft. No significant change in use of BM versus PB grafts occurred after 2012. Both BMT CTN participating and nonparticipating centers continued to use PB. Ninety-two percent of respondents were aware of the study results; 18% reported a change in personal and 16% reported a change in their center's practice of requesting BM instead of PB for URD HCT. Patient characteristics and the perception that engaging local champions to increase the evidence uptake were factors associated with personal or center change in practice. Despite awareness of the trial results, fewer than one-fifth of HCT physicians reported practice change in response to the BMT CTN 0201 results. Observational data confirmed no discernible change in practice.

SUBMITTER: Khera N

PROVIDER: S-EPMC6242749 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Translation of Clinical Research into Practice: An Impact Assessment of the Results from the Blood and Marrow Transplant Clinical Trials Network Protocol 0201 on Unrelated Graft Source Utilization.

Khera Nandita N Mau Lih-Wen LW Denzen Ellen M EM Meyer Christa C Houg Kate K Lee Stephanie J SJ Horowitz Mary M MM Burns Linda J LJ

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20180630 11

Barriers and facilitators to adoption of results of clinical trials are substantial and poorly understood. We sought to examine whether the results of the randomized, multicenter Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 study comparing peripheral blood (PB) with bone marrow (BM) stem cells for unrelated donor (URD) hematopoietic cell transplantation (HCT) changed practice from PB to BM graft utilization and explored factors that impact graft selection and translation of ...[more]

PMID: 29966761

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Project description:We report a comparison of time to recovery, side effects, and change in blood counts from baseline to after donation from unrelated donors who participated in the Blood and Marrow Transplant Clinical Trials Network phase III randomized, multicenter trial (0201) in which donor-recipient pairs were randomized to either peripheral blood stem cell (PBSC) or bone marrow (BM) donation. Of the entire cohort, 262 donated PBSC and 264 donated BM; 372 (71%) donors were from domestic and 154 (29%) were from international centers (145 German and 9 Canadian). PBSC donors recovered in less time, with a median time to recovery of 1 week compared with 2.3 weeks for BM donors. The number of donors reporting full recovery was significantly greater for donors of PBSC than of BM at 1, 2, and 3 weeks and 3 months after donation. Multivariate analysis showed that PBSC donors were more likely to recover at any time after donation compared with BM donors (hazard ratio, 2.08; 95% confidence interval [CI], 1.73 to 2.50; P < .001). Other characteristics that significantly increased the likelihood of complete recovery were being an international donor and donation in more recent years. Donors of BM were more likely to report grades 2 to 4 skeletal pain, body symptoms, and fatigue at 1 week after donation. In logistic regression analysis of domestic donors only in which toxicities at peri-collection time points (day 5 filgrastim for PBSC donors and day 2 after collection of BM donors) could be analyzed, no variable was significantly associated with grades 2 to 4 skeletal pain, including product donated (BM versus PBSC; odds ratio, 1.13; 95% CI, .74 to 1.74; P = .556). Blood counts were affected by product donated, with greater mean change from baseline to after donation for white blood cells, neutrophils, mononuclear cells, and platelets in PBSC donors whereas BM donors experienced a greater mean change in hemoglobin. This analysis provided an enhanced understanding of donor events as product donated was independent of physician bias or donor preference.

Project description:BackgroundDrug-laboratory (lab) interactions (DLIs) are a common source of preventable medication errors. Clinical decision support systems (CDSSs) are promising tools to decrease such errors by improving prescription quality in terms of lab values. However, alert fatigue counteracts their impact. We aimed to develop a novel user-friendly, evidence-based, clinical context-aware CDSS to alert nephrologists about DLIs clinically important lab values in prescriptions of kidney recipients.MethodsFor the most frequently prescribed medications identified by a prospective cross-sectional study in a kidney transplant clinic, DLI-rules were extracted using main pharmacology references and clinical inputs from clinicians. A CDSS was then developed linking a computerized prescription system and lab records. The system performance was tested using data of both fictitious and real patients. The "Questionnaire for User Interface Satisfaction" was used to measure user satisfaction of the human-computer interface.ResultsAmong 27 study medications, 17 needed adjustments regarding renal function, 15 required considerations based on hepatic function, 8 had drug-pregnancy interactions, and 13 required baselines or follow-up lab monitoring. Using IF & THEN rules and the contents of associated alert, a DLI-alerting CDSS was designed. To avoid alert fatigue, the alert appearance was considered as interruptive only when medications with serious risks were contraindicated or needed to be discontinued or adjusted. Other alerts appeared in a non-interruptive mode with visual clues on the prescription window for easy, intuitive notice. When the system was used for real 100 patients, it correctly detected 260 DLIs and displayed 249 monitoring, seven hepatic, four pregnancy, and none renal alerts. The system delivered patient-specific recommendations based on individual lab values in real-time. Clinicians were highly satisfied with the usability of the system.ConclusionsTo our knowledge, this is the first study of a comprehensive DLI-CDSS for kidney transplant care. By alerting on considerations in renal and hepatic dysfunctions, maternal and fetal toxicity, or required lab monitoring, this system can potentially improve medication safety in kidney recipients. Our experience provides a strong foundation for designing specialized systems to promote individualized transplant follow-up care.

Project description:PurposeHematopoietic cell transplantation (HCT) is curative for hematologic disorders, but outcomes are historically inferior when using HLA-mismatched donors. Despite unrelated donor registries listing > 38 million volunteers, 25%-80% of US patients lack an HLA-matched unrelated donor, with significant disparity across ethnic groups. We hypothesized that HCT with a mismatched unrelated donor (MMUD) using post-transplant cyclophosphamide (PTCy), a novel strategy successful in overcoming genetic disparity using mismatched related donors, would be feasible and increase access to HCT.Patients and methodsWe performed a prospective phase II study of MMUD bone marrow HCT with PTCy for patients with hematologic malignancies. The primary end point was 1-year overall survival (OS), hypothesized to be 65% or better. 80 patients enrolled at 11 US transplant centers (December 2016-March 2019). Following myeloablative or reduced-intensity conditioning-based HCT, patients received PTCy on days +3, +4, with sirolimus and mycophenolate mofetil starting on day +5. We compared outcomes to Center for International Blood and Marrow Transplant Research contemporary controls receiving PTCy.ResultsNotably, 48% of patients enrolled were ethnic minorities. 39% of pairs were matched for 4-6 out of 8 HLA alleles. The primary end point was met, with 1-year OS of 76% (90% CI, 67.3 to 83.3) in the entire cohort, and 72% and 79% in the myeloablative and reduced-intensity conditioning strata, respectively. Secondary end points related to engraftment and graft-versus-host-disease were reached. Multivariate analysis comparing the study group with other mismatched HCT controls found no significant differences in OS.ConclusionOur prospective study demonstrates the feasibility and effectiveness of HCT with an MMUD in the setting of PTCy. Remarkably, nearly half of the study participants belonged to an ethnic minority population, suggesting this approach may significantly expand access to HCT.

Project description:There are limited data as to the effectiveness of mycophenolate mofetil (MMF) plus high-dose corticosteroids for the treatment of acute graft-versus-host disease (aGVHD), and even less data regarding the pharmacokinetic disposition and exposure-response relationship of MMF in individuals with GVHD. MMF pharmacokinetics were studied in a multicenter Blood and Marrow Transplant Clinical Trials Network randomized phase II trial evaluating the effectiveness of MMF as one of 4 agents added to corticosteroids as treatment of aGVHD. Thirty-two of the patients randomized to receive MMF underwent pharmacokinetic sampling in weeks 1 and 2 were studied. Mean age was 41 +/- 13.6 years. Twenty one (65.6%), 5 (15.6%), 6 (18.8%) patients had a complete response (CR), partial response (PR) or lesser response by day 28, respectively. Twenty-five (78.1%), 2 (6.3%), 5 (15.6%) patients had a CR, PR, or other response by day 56 to treatment, respectively. Mycophenolic acid (MPA) pharmacokinetic measurements from weeks 1 and 2 did not correlate with CR at either day 28 or day 56 (P > .07); however, if the mean of weeks 1 and 2 total MPA troughs was >0.5 microg/mL or that of an unbound trough was >0.015 microg/mL, then a significantly greater proportion achieved CR + PR at days 28 and 56. CR + PR at day 28 was observed in 19 of 19 patients (100%) with a mean total trough >0.5 mg/mL, but in only 7 of 13 (54%) with a mean total trough < or =0.5 microg/mL (P = .002). Similarly, CR + PR at day 28 was seen in 15 of 15 patients (100%) with an unbound trough concentration >0.015 microg/mL, but in only 11 of 17 (65%) with an unbound trough concentration < or =0.015 microg/mL (P = .02). There was no association between the pharmacokinetic measures and risk of infection by day 90 or overall survival (OS) at day 180 postrandomization. About one-half of subjects did not achieve the favorable MPA total and unbound trough concentrations. The current practice of MMF 1 gm twice daily dosing provides low plasma concentrations in many patients. Higher doses may improve the efficacy of MMF as aGVHD therapy.

Dataset Information

Translation of Clinical Research into Practice: An Impact Assessment of the Results from the Blood and Marrow Transplant Clinical Trials Network Protocol 0201 on Unrelated Graft Source Utilization.

Publications

Translation of Clinical Research into Practice: An Impact Assessment of the Results from the Blood and Marrow Transplant Clinical Trials Network Protocol 0201 on Unrelated Graft Source Utilization.

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