Quality of life and cost-effectiveness of convalescent plasma compared to standard care for hospitalized COVID-19 patients in the CONCOR-1 trial.

BACKGROUND: The CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1) trial was a multicenter randomized controlled trial assessing convalescent plasma in hospitalized COVID-19 patients. This study evaluates the cost-effectiveness of convalescent plasma and its impact on quality-of-life to provide insight into its potential as an alternative treatment in resource-constrained settings. METHODS: Individual patient data on health outcomes and resource utilization from the CONCOR-1 trial were used to conduct the analysis from the Canadian public payer's perspective with a time horizon of 30 days post-randomization. Baseline and 30-day EQ-5D-5L were measured to calculate quality-adjusted survival. All costs are presented in 2021 Canadian dollars. The base case assessed the EQ-5D-5L scores of hospitalized inpatients reporting at both timepoints, and a utility score of 0 was assigned for patients who died within 30 days. Costs for all patients enrolled were used. The sensitivity analysis utilizes EQ-5D-5L scores from the same population but only uses costs from this population. RESULTS: 940 patients were randomized: 627 received CCP and 313 received standard care. The total costs were $28,716 (standard deviation, $25,380) and $24,258 ($22,939) for the convalescent plasma and standard care arms respectively. EQ-5D-5L scores were 0.61 in both arms (p = .85) at baseline. At 30 days, EQ-5D-5L scores were 0.63 and 0.64 for patients in the convalescent plasma and standard care arms, respectively (p = .46). The incremental cost was $4458 and the incremental quality-adjusted life day was -0.078. DISCUSSION: Convalescent plasma was less effective and more costly than standard care in treating hospitalized COVID-19.

Cost-effectiveness of eltrombopag vs intravenous immunoglobulin for the perioperative management of immune thrombocytopenia.

Eltrombopag has been shown to be noninferior to intravenous immunoglobulin (IVIG) for improving perioperative platelet counts in patients with immune thrombocytopenia (ITP) in a randomized trial; thus, cost is an important factor for treatment and policy decisions. We used patient-level data from the trial to conduct a cost-effectiveness analysis comparing perioperative eltrombopag 50 mg daily starting dose, with IVIG 1 or 2 g/kg (according to local practice) from a Canadian public health care payer's perspective over the observation period, from preoperative day 21 to postoperative day 28. Resource utilization data were obtained from the trial data (eltrombopag, n = 38; IVIG, n = 36), and unit costs were collected from the Ontario Schedule of Benefits, Ontario Drug Formulary, and secondary sources. All costs were adjusted to 2020 Canadian dollars. We calculated the incremental cost per patient for all patients randomized. Uncertainty was addressed using nonparametric bootstrapping. The use of perioperative eltrombopag for patients with ITP resulted in a cost-saving of $413 Canadian per patient. Compared with IVIG, the probability of eltrombopag being cost effective was 70% even with no willingness to pay. In a sensitivity analysis based on IVIG dose, we found that with the higher dose of IVIG (2 g/kg), eltrombopag saved $2,714 per patient, whereas with the lower dose of IVIG (1 g/kg), eltrombopag had a higher mean cost of $562 per patient. In summary, based on data from the randomized trial that demonstrated noninferiority, the use of eltrombopag for the management of ITP in the perioperative setting was less costly than IVIG.

An international investigation into AB plasma administration in hospitals: how many AB plasma units were infused? The HABSWIN study.

BACKGROUND: Typical practice is to transfuse group-specific plasma units; however, there are situations where group AB plasma (universal donor) is issued to group A, B, or O recipients. If demand for group AB plasma exceeds collections, there is potential for shortage. This project explored the patterns of group AB plasma utilization at hospitals around the world. STUDY DESIGN AND METHODS: The study had two phases: a survey that inquired about hospital group AB plasma inventory, policies, and transfusion practices and a retrospective review of 2014 calendar year data where participants submitted information on plasma disposition including ABO group of unit and recipient, transfusion location, and select indications. Recruitment occurred through snowball sampling. Descriptive analyses were performed. RESULTS: Survey data were received from 25 centers across 10 countries; of those, 15 participants contributed to the data collection component. These 15 centers transfused a total of 43,369 AB plasma units during the study period. Only 1496 of 5541 (27%) group AB plasma units were transfused to group AB recipients. Transfusion policies, practices, and patterns were variable across sites. CONCLUSION: Group AB plasma units are frequently transfused to non-AB recipients. Whether transfusing 73% of group AB plasma units to non-AB recipients is the ideal inventory management strategy remains to be determined.

External validation of a risk assessment model for venous thromboembolism in the hospitalised acutely-ill medical patient (VTE-VALOURR).

Venous thromboembolic (VTE) risk assessment remains an important issue in hospitalised, acutely-ill medical patients, and several VTE risk assessment models (RAM) have been proposed. The purpose of this large retrospective cohort study was to externally validate the IMPROVE RAM using a large database of three acute care hospitals. We studied 41,486 hospitalisations (28,744 unique patients) with 1,240 VTE hospitalisations (1,135 unique patients) in the VTE cohort and 40,246 VTE-free hospitalisations (27,609 unique patients) in the control cohort. After chart review, 139 unique VTE patients were identified and 278 randomly-selected matched patients in the control cohort. Seven independent VTE risk factors as part of the RAM in the derivation cohort were identified. In the validation cohort, the incidence of VTE was 0.20%; 95% confidence interval (CI) 0.18-0.22, 1.04%; 95%CI 0.88-1.25, and 4.15%; 95%CI 2.79-8.12 in the low, moderate, and high VTE risk groups, respectively, which compared to rates of 0.45%, 1.3%, and 4.74% in the three risk categories of the derivation cohort. For the derivation and validation cohorts, the total percentage of patients in low, moderate and high VTE risk occurred in 68.6% vs 63.3%, 24.8% vs 31.1%, and 6.5% vs 5.5%, respectively. Overall, the area under the receiver-operator characteristics curve for the validation cohort was 0.7731. In conclusion, the IMPROVE RAM can accurately identify medical patients at low, moderate, and high VTE risk. This will tailor future thromboprophylactic strategies in this population as well as identify particularly high VTE risk patients in whom multimodal or more intensive prophylaxis may be beneficial.

Individual and contextual determinants of blood donation frequency with a focus on clinic accessibility: a case study of Toronto, Canada.

The balance between supply and demand of blood products is a question of great interest for the long-term prospects of health care systems. Trends that affect this balance include an aging population and increasingly large immigrant communities with lower donation rates. Blood agencies must implement several strategies to ensure a sustained supply of blood products. A better understanding of the determinants of donation frequency is essential to develop strategies that encourage new and existing donors to donate more frequently. In this study, we investigate the individual and contextual determinants of the decision to donate multiple times, with a particular focus on accessibility to clinics. The case study is the Toronto Census Metropolitan Area. Analysis is based on discrete choice models estimated using the attributes of the geocoded donors and clinics, and Census data for contextual variables. The results indicate that higher levels of accessibility increase the probability of donor return and more frequent donations.

Forecasting Ontario's blood supply and demand.

BACKGROUND: Given an aging population that requires increased medical care, an increasing number of deferrals from the donor pool, and a growing immigrant population that typically has lower donation rates, the purpose of this article is to forecast Ontario's blood supply and demand. STUDY DESIGN AND METHODS: We calculate age- and sex-specific donation and demand rates for blood supply based on 2008 data and project demand between 2008 and 2036 based on these rates and using population data from the Ontario Ministry of Finance. RESULTS: Results indicate that blood demand will outpace supply as early as 2012. For instance, while the total number of donations made by older cohorts is expected to increase in the coming years, the number of red blood cell (RBC) transfusions in the 70+ age group is forecasted grow from approximately 53% of all RBC transfusions in 2008 (209,515) in 2008 to 68% (546,996) by 2036. A series of alternate scenarios, including projections based on a 2% increase in supply per year and increased use of apheresis technology, delays supply shortfalls, but does not eliminate them without active management and/or multiple methods to increase supply and decrease demand. CONCLUSIONS: Predictions show that demand for blood products will outpace supply in the near future given current age- and sex-specific supply and demand rates. However, we note that the careful management of the blood supply by Canadian Blood Services, along with new medical techniques and the recruitment of new donors to the system, will remove future concerns.

Do expert assessments converge? An exploratory case study of evaluating and managing a blood supply risk.

BACKGROUND: Examining professional assessments of a blood product recall/withdrawal and its implications for risk and public health, the paper introduces ideas about perceptions of minimal risk and its management. It also describes the context of publicly funded blood transfusion in Canada and the withdrawal event that is the basis of this study. METHODS: Interviews with 45 experts from administration, medicine, blood supply, laboratory services and risk assessment took place using a multi-level sampling framework in the aftermath of the recall. These experts either directly dealt with the withdrawal or were involved in the management of the blood supply at the national level. Data from these interviews were coded in NVivo for analysis and interpretation. Analytically, data were interpreted to derive typifications to relate interview responses to risk management heuristics. RESULTS: While all those interviewed agreed on the importance of patient safety, differences in the ways in which the risk was contextualized and explicated were discerned. Risk was seen in terms of patient safety, liability or precaution. These different risk logics are illustrated by selected quotations. CONCLUSIONS: Expert assessments did not fully converge and it is possible that these different risk logics and discourses may affect the risk management process more generally, although not necessarily in a negative way. Patient safety is not to be compromised but management of blood risk in publicly funded systems may vary. We suggest ways of managing blood risk using formal and safety case approaches.

Diagnostic usefulness of a lumi-aggregometer adenosine triphosphate release assay for the assessment of platelet function disorders.

Platelet dense granule release assays are recommended for diagnosing platelet function disorders and are commonly performed by Lumi-Aggregometer (Chrono-Log, Havertown, PA) assays of adenosine triphosphate (ATP) release. We conducted a prospective cohort study of people tested for ATP release defects to assess bleeding symptoms. Reduced release, with 1 or more agonists, was more common among patients with bleeding disorders than among healthy control subjects (P < .001). The respective likelihood (odds ratio [95% confidence interval]) of a bleeding disorder or an inherited platelet function disorder were high when release was reduced with 1 or more agonists (17 [6-46]; 128 [30-545]), even if aggregation was normal (12 [4-34]; 105 [20-565]). ATP release had high specificity and moderate sensitivity for inherited platelet function disorders, with most abnormalities detected by the combination of 6 µmol/L epinephrine, 5.0 µg/mL collagen, and 1 µmol/L U46619. Platelet ATP release assays are useful for evaluating common bleeding disorders, regardless of aggregation findings.

A systematic assessment of the quality of reporting for platelet transfusion studies.

BACKGROUND: As evidence-based medicine assumes increasing importance, there is a need for high-quality reporting of clinical studies. A recent review of clinical platelet (PLT) studies indicated variability in reporting. We undertook a critical analysis of PLT transfusion studies to determine the quality of reporting. STUDY DESIGN AND METHODS: A systematic MEDLINE search for clinical studies of PLT transfusion was performed to identify articles. Relevant observational studies (OBS) were critiqued using the STROBE checklist and randomized controlled clinical trials (RCTs) using the CONSORT checklist. Studies were further evaluated with a PLT-specific checklist developed by the authors. Observations were analyzed descriptively and using Pareto analysis. RESULTS: A total of 772 articles were identified by the search. Eighty-six articles (23 RCTs and 63 OBS) met eligibility criteria. All RCTs, and a similar number of OBS (24), were randomly selected for analysis. Studies reported the scientific background and rationale, key results, and outcomes. OBS frequently did not consider bias and confounders. RCTs frequently did not explain bias, interim analyses, stopping rules, success of blinding, or weaknesses of multiple analyses. The PLT-specific critique found many studies adequately reported basics of the PLT product, PLT increment, and transfusion reactions. Studies frequently failed to report specific details of PLT compatibility, details of product preparation, and use of other blood products. CONCLUSION: Recently published articles of clinical PLT transfusion share common strengths and weaknesses. The quality of reporting may be improved by providing guidelines to authors and journal editors that list the essential elements of a well-reported clinical study of PLT transfusion.

Geographical variations in the correlates of blood donor turnout rates: an investigation of Canadian metropolitan areas.

BACKGROUND: Like other countries, Canada's population is aging, and the implications of this demographic change need to be better understood from the perspective of blood supply. Analysis of donor data will help to identify systematic patterns of donation and its correlates. DATA: Geo-coded blood donor and donor clinic data are provided by Canadian Blood Services. Blood donor data is provided for the fiscal year 2006-2007 indicating the total number of donors for each Canadian postal code, excluding the province of Québec. Potential correlates of blood donation are selected based on social and economic characteristics, as well as descriptors of city size and geographical location in the urban hierarchy measures of accessibility, and capacity of donor clinics. METHODS: Data is aggregated to n = 3,746 census tracts in 40 Census Metropolitan Areas (CMA) across the country. The number of donors per population in a census tract is regressed against the set of potential donation correlates. Autocorrelation is tested for and results adjusted to provide parsimonious models. RESULTS: A number of factors are found to influence donation across the country, including the proportion of younger residents, English ability, proportion of people with immigrant status, higher education, and a population-based measure of accessibility. CONCLUSION: While a number of correlates of blood donation are observed across Canada, important contextual effects across metropolitan areas are highlighted. The paper concludes by looking at policy options that are aimed toward further understanding donor behaviour.

A study of the agreement between patient self-assessment and study personnel assessment of bleeding symptoms.

BACKGROUND: Clinical trials investigating new platelet transfusion therapies frequently require the assessment of bleeding for the study outcome. These assessments are commonly performed by study personnel and can be time-consuming. The purpose of this study was to assess whether patients were able to reliably assess their bleeding status on a daily basis. STUDY DESIGN AND METHODS: Patients admitted to hospital to receive chemotherapy for acute leukemia or to undergo allogeneic peripheral blood progenitor cell transplant were included. Patients were given an introduction to a form for documenting the occurrence of 16 bleeding symptoms. Patients completed this form and were examined daily by a study assessor. A weekly health record review was also performed by a study assessor. The agreement between raters was determined by calculating the raw agreement, chance-corrected agreement, and chance-independent agreement. RESULTS: Thirty-five patients completed 458 assessment forms that were paired with 559 forms completed by a study assessor with 450 matched forms available for analysis (mean, 12.86 per patient). Agreement for most individual bleeding symptoms was high. Thirteen items had agreement greater than 90 percent and all items had agreement greater than 77 percent. The lowest agreement was seen for skin symptoms: petechiae (89.2%), purpura (80.9%), and ecchymosis (77.6%). The negative predictive value of patient self-assessment was high (range, 71.1%-100%) whereas the positive predictive value was lower (range, 0%-86.5%). CONCLUSION: The reliability was very good between patients and study assessors with the patients reporting excellent negative predictive value and variable positive predictive value.

Developing a tracking system for coagulation factor concentrates in southern Ontario.

BACKGROUND: In response to the transfusion- transmitted AIDS epidemic, Canadian authorities recommended the development of tracking systems and improved reporting of adverse events. This study describes the development of a verifiable and comprehensive regional tracking system for coagulation factor concentrates. STUDY DESIGN AND METHODS: The Hamilton- Niagara Regional Hemophilia Program received distribution and utilization data from Canadian Blood Services, 26 regional hospitals, and 70 individuals with bleeding disorders on home-based therapy. Purpose-specific software, the Canadian Hemophilia Assessment and Resource Management System (CHARMS), was used to store, monitor, analyze, and validate data. RESULTS: During a 1-year period (2001), all factor concentrates distributed in this region were accounted for. A higher proportion of FVIII and FIX concentrates (88 vs. 12%) was infused at home than in hospitals, and a higher proportion (63 vs. 28%) was used to prevent than to treat bleeds. During a period of shortage, a 5-percent reduction in utilization of both FVIII and FIX concentrates was documented. One recall was managed swiftly and efficiently. Two patients reported allergic skin reactions. CONCLUSION: A verifiable tracking system has been developed that can provide ongoing data for both clinical and administrative purposes. Data collection from patients needs to be made more efficient and real-time recording is an important future objective. Such a system can be instituted locally for less than 1.5 percent of the cost of the factor concentrate used.