Background
Clinical decision‐making for patients with myelodysplastic syndromes (MDS) is challenging, and both disease and treatment effects heavily impact health‐related quality of life (HRQoL) of ...these patients. Therefore, disease‐specific HRQoL measures can be critical to harness the patient voice in MDS research.
Methods
We report a prospective international validation study of the Quality of Life in Myelodysplasia Scale (QUALMS) with a main focus on providing information on the psychometric characteristics of its three subscales: physical burden (QUALMS‐P), emotional burden (QUALMS‐E), and benefit finding (QUALMS‐BF). The analysis is based on patients enrolled from three European countries and Israel, participating to the MDS‐RIGHT Project. The scale structure and psychometric properties of the QUALMS were assessed.
Results
Overall, 270 patients with a median age of 74 years were analyzed and the majority of them (60.3%) had a low MDS‐Comorbidity Index score. Results of the confirmatory factor analysis supported the underlying scale structure of the QUALMS, which, in addition to a total score, includes three subscales: QUALMS‐P, QUALMS‐E, and the QUALMS‐BF. The QUALMS‐P exhibited the highest Cronbach's alpha coefficients. Discriminant validity analysis indicated good results with the QUALMS‐P and QUALMS‐E distinguishing between patients with different performance status, comorbidity, anemia, and transfusion dependency status. No floor and ceiling effects were observed. Responsiveness to change analysis supported the validity of the measure. Patients with a hemoglobin (Hb) level of <11 g/dL at study entry, who subsequently showed an improvement in their Hb levels, also reported a mean score change of 9 and 8 points (scales ranging between 0 and 100) in the expected direction of the QUALMS‐E and QUALMS‐P, respectively.
Conclusions
Our study provides additional validation data on the QUALMS from the international MDS‐RIGHT Project. The use of this disease‐specific HRQoL measure may contribute to raise quality standards of patient‐centered outcomes research in MDS.
The QUALMS is a Patient‐Reported Outcome measure to assess health‐related quality of life in patients with myelodysplastic syndromes. This study, conducted across three European countries and Israel, supports the validity of the QUALMS and provides novel information on the psychometric performance of its three subscales (QUALMS‐P; QUALMS‐E; QUALMS‐BF).
(1) Background: The Austrian supply of COVID-19 vaccine is limited for now. We aim to provide evidence-based guidance to the authorities in order to minimize COVID-19-related hospitalizations and ...deaths in Austria. (2) Methods: We used a dynamic agent-based population model to compare different vaccination strategies targeted to the elderly (65 ≥ years), middle aged (45-64 years), younger (15-44 years), vulnerable (risk of severe disease due to comorbidities), and healthcare workers (HCW). First, outcomes were optimized for an initially available vaccine batch for 200,000 individuals. Second, stepwise optimization was performed deriving a prioritization sequence for 2.45 million individuals, maximizing the reduction in total hospitalizations and deaths compared to no vaccination. We considered sterilizing and non-sterilizing immunity, assuming a 70% effectiveness. (3) Results: Maximum reduction of hospitalizations and deaths was achieved by starting vaccination with the elderly and vulnerable followed by middle-aged, HCW, and younger individuals. Optimizations for vaccinating 2.45 million individuals yielded the same prioritization and avoided approximately one third of deaths and hospitalizations. Starting vaccination with HCW leads to slightly smaller reductions but maximizes occupational safety. (4) Conclusion: To minimize COVID-19-related hospitalizations and deaths, our study shows that elderly and vulnerable persons should be prioritized for vaccination until further vaccines are available.
Evidence on long-term effectiveness and cost effectiveness of treatment sequences for multiple myeloma (MM) is sparse. We used published data and country-specific data to assess the cost ...effectiveness of four-line treatment sequences for elderly transplant-ineligible patients with MM in Serbia.
We developed a Markov cohort model to compare long-term effectiveness and cost effectiveness of five sequential MM treatment alternatives from the perspective of the national healthcare provider. Effectiveness parameters on progression, mortality and adverse events were extracted from published clinical trials. Costs were based on price lists of the National Health Insurance Fund. We compared life expectancy, costs, and incremental cost-effectiveness ratios among alternative courses of action. The model was analyzed over a lifelong time horizon applying a 3% annual discount rate for effectiveness outcomes and costs. Robustness of the model was tested in multiple deterministic sensitivity analyses.
The sequences were defined by the frontline treatment: MPT (melphalan-prednisone-thalidomide), MPV (melphalanprednisone-bortezomib), CTD (cyclophosphamide-thalidomide-dexamethasone), VCD (bortezomib-cyclophosphamidedexamethasone) and BP (bendamustine-prednisone). MPV sequence resulted in the highest remaining life expectancy (4.76 life years). Cost-effectiveness analysis resulted in three non-dominated strategies: MPT, VCD, and MPV sequences, with an incremental cost-effectiveness ratio of EUR 35,300 per life-year gained (LYG) for VCD and EUR 47,200/LYG for MPV relative to MPT.
MPV sequence was the most effective in terms of life expectancy for elderly transplant-ineligible MM patients in Serbia. Bortezomib-based strategies would be recommended for the frontline treatment of patients with MM in Serbia if the willingness-to-pay threshold is around EUR 35,000-60,000/LYG.
Introduction
Damage to the central nervous system (CNS) in adulthood, may lead to cognitive impairments. In Germany, occupational therapy is most often prescribed for neurological diagnoses, ...including stroke and traumatic brain injury (351 and 343 cases per 100,000, respectively in 2018). For cognitive impairments, the primarily prescribed remedies are sensorimotor-perceptive, motor-functional and neuropsychologically oriented treatment or training of cognitive performance. Here we report the results of a health technology assessment (HTA) report on the clinical efficacy of occupational therapy for patients with cognitive impairments.
Methods
To assess clinical efficacy, a systematic overview was conducted based on published systematic reviews and HTA reports from the last ten years summarizing randomized controlled trials (RCTs) retrieved from four bibliographic databases. The target population included adult patients with cognitive impairments caused by diseases of the CNS, excluding moderate to severe dementia. The intervention studied is occupational therapy compared to no occupational therapy. Outcomes were cognitive abilities, independence, self-determination, health-related quality of life (QoL), and participation in activities of daily living (ADL).
Results
Five systematic reviews comprising 1,316 patients were included. There is evidence for a small statistically significant positive effect on “general cognitive function” (10 RCTs, n=470) and on ADL (4 RCTs, n= 405). A non-quantified positive effect was reported on behavior control (1 RCT, n=96), and conflicting evidence on QoL (2 RCTs, n=214). No effect was found for individual components of cognition (5 RCTs, n=202), self-efficacy (1 RCT, n=98) and social participation (2 RCTs, n=194). The level of the evidence was low for all endpoints due to the high risk of bias and small sample sizes.
Conclusions
Based on this systematic overview, it cannot be demonstrated but also not ruled out that occupational therapy for cognitive impairment is an effective therapy for adults with cognitive impairments. The evidence is very uncertain due to small effects and high risk of bias, low statistical power, and heterogeneity of interventions and study populations.
FH is still underdiagnosed. Cost-effectiveness results of preventive screening strategies vary. We aimed at systematically assessing the benefits, harms and cost effectiveness of screening for ...familial hypercholesterolemia (FH) and at providing an overview of the main characteristics and methodological approaches of applied decision-analytic models.
A systematic literature search was conducted in MEDLINE, EconLit, CRD-databases and the CEA-registry for FH screening starting 2012. Earlier studies were included from a published systematic review. Results were reported in standardized semi-quantitative evidence tables. Costs were converted to current euros. Incremental cost-effectiveness ratios (ICERs) were recalculated according to economic guidelines.
Out of our 211 retrieved studies, eight were included in the review in addition to six studies from an earlier review. Studies were conducted in Europe (UK, The Netherlands, Spain, Poland), USA and Australia evaluating cascade (CS), opportunistic (OS), universal screening (UniS), or combinations using genetic testing, clinical criteria or combinations. Studies evaluating only CS identified strategies with an ICER of up to 37,100 EUR/quality-adjusted life-year (QALY) but some strategies were dominated depending on test combinations. UniS of newborns in combination with CS had an ICER≤15,000 EUR/QALY for sequential cholesterol-genetic screening. In other studies, UniS was dominated by OS/CS.
Our systematic review demonstrates the values of FH screening and provides an overview of potentially relevant screening strategies to be tested using a decision-analytic model for the respective country or region. Future research is needed on the transferability of results to other countries and modeling spillover effects to newborns.
Display omitted
•Familial hypercholesterolemia is still underdiagnosed even if various screening strategies have been investigated/applied.•Many cascade-screening programs appear to be cost effective (at threshold <40,000 EUR/quality-adjusted life-year gained).•There is no consistent evidence on cost effectiveness of universal screening and opportunistic screening.•Future research is needed on transferability to other countries and modeling spillover effects to newborns.
Drawing causal conclusions from real-world data (RWD) poses methodological challenges and risk of bias. We aimed to systematically assess the type and impact of potential biases that may occur when ...analyzing RWD using the case of progressive ovarian cancer.
We retrospectively compared overall survival with and without second-line chemotherapy (LOT2) using electronic medical records. Potential biases were determined using directed acyclic graphs. We followed a stepwise analytic approach ranging from crude analysis and multivariable-adjusted Cox model up to a full causal analysis using a marginal structural Cox model with replicates emulating a reference randomized controlled trial (RCT). To assess biases, we compared effect estimates (hazard ratios HRs) of each approach to the HR of the reference trial.
The reference trial showed an HR for second line vs. delayed therapy of 1.01 (95% confidence interval 95% CI: 0.82–1.25). The corresponding HRs from the RWD analysis ranged from 0.51 for simple baseline adjustments to 1.41 (95% CI: 1.22–1.64) accounting for immortal time bias with time-varying covariates. Causal trial emulation yielded an HR of 1.12 (95% CI: 0.96–1.28).
Our study, using ovarian cancer as an example, shows the importance of a thorough causal design and analysis if one is expecting RWD to emulate clinical trial results.
•To assess potential biases in real-world evidence (RWE), this paper compares the hazards ratio (HRs) of the reference trial to the estimated HRs following different analytic approaches.•Biases resulting from the different analytic approaches varied in size and direction, ranging from 75% underestimating the HR to 36% overestimating the HR.•The full causal analysis (including the target trial emulation using a marginal-structural-Cox-model) yielded the smallest bias, overestimating the HR by 10%.•In RWE, a thorough causal-inference-based design and analysis is important.
Objectives
This study aims to describe the use of patient‐reported outcome measures (PROMs) in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) studies and the PROMs landscape.
...Methods
A comprehensive literature review was performed in Medline/Embase (since 2000) and ClinicalTrials.gov (since 2013) to identify PROMs used in MDS and AML clinical studies. Additionally, PROMs included in approved drug labels since 2000 were reviewed.
Results
Overall, 112 different PROMs were used in 168 published MDS studies and 152 PROMs were used in 172 AML studies. From ClinicalTrials.gov, 16 different PROMs were used in 22 ongoing registered studies in MDS, and 24 were reported in 41 AML studies. The most frequently used PROMs were cancer‐specific (eg, EORTC QLQ‐C30, FACT‐An) or generic (SF‐36, EQ‐5D) instruments, whereas MDS‐ and AML‐specific instruments (eg, QUALMS and QOL‐E in MDS; FACT‐Leu and EORTC QLQ‐Leu in AML) were used in a minority of studies. Two EMA‐approved drugs for MDS included PROMs in their label. EORTC QLQ‐C30 is by far the most frequently used cancer‐specific PROM in both MDS and AML studies.
Conclusions
This research indicated an underuse of AML/MDS‐specific PROMs for these two indications in clinical studies and labeling claims. However, AML/MDS‐specific instruments in development might be considered in future studies.
Summary
Treatment options for myelodysplastic syndromes (MDS) vary widely, depending on the natural disease course and patient‐related factors. Comparison of treatment effectiveness is challenging as ...different endpoints have been included in clinical trials and outcome reporting. Our goal was to develop the first MDS core outcome set (MDS‐COS) defining a minimum set of outcomes that should be reported in future clinical studies. We performed a comprehensive systematic literature review among MDS studies to extract patient‐ and/or clinically relevant outcomes. Clinical experts from the European LeukemiaNet MDS (EUMDS) identified 26 potential MDS core outcomes and participated in a three‐round Delphi survey. After the first survey (56 experts), 15 outcomes met the inclusion criteria and one additional outcome was included. The second round (38 experts) resulted in six included outcomes. In the third round, a final check on plausibility and practicality of the six included outcomes and their definitions was performed. The final MDS‐COS includes: health‐related quality of life, treatment‐related mortality, overall survival, performance status, safety, and haematological improvement. This newly developed MDS‐COS represents the first minimum set of outcomes aiming to enhance comparability across future MDS studies and facilitate a better understanding of treatment effectiveness.
Damage to the central nervous system can occur in adulthood, for example, due to stroke, trauma, tumours, or chronic diseases. After damage to the central nervous system, cognitive impairments occur ...in addition to physical limitations. Occupational therapy is most often prescribed for neurological diagnoses, including stroke and traumatic brain injury.
The health technology assessment (HTA) report this HTA article is based on investigates the clinical effectiveness, cost-effectiveness, and patient-related, social and ethical aspects of occupational therapy for patients with cognitive impairments compared to no occupational therapy. In addition, the effects of different occupational therapy interventions with and without cognitive components were compared in an explorative overview. Patients with moderate or severe dementia are excluded from the assessment. Systematic overviews, that is, systematic reviews of systematic reviews, were conducted.
For the evaluation of clinical effectiveness, a total of nine systematic reviews were included. No systematic review was identified for the assessment of costs or cost-effectiveness. Five systematic reviews were included for the assessment of patient and social aspects. For the assessment of clinical effectiveness compared with no occupational therapy, five systematic reviews comprising 20 randomised controlled trials with a total of 1,316 subjects reported small positive effects for the outcomes "global cognitive function" and "activities of daily living" as well as a non-quantified positive effect on the outcomes "health-related quality of life" and "behavioural control". No effect was found for individual components of cognition and measures of perception. The quality of the evidence for all outcomes is low due to a high risk of bias. In the supplementary presentations, no positive effects could be demonstrated on the basis of the available evidence. The quality of this evidence was not assessed. For the assessment of patient and social aspects, five systematic reviews on patients with a stroke or a traumatic brain injury - without specification regarding cognitive deficits or studies with their relatives - were included. It was reported that patients and family caregivers go through different phases of rehabilitation in which the discharge home is a decisive turning point. The discharge home represents a crucial breaking point. Regaining an active, self-determining role is a process that requires therapists to find the right level of support for patients and relatives. For the assessment of ethical aspects, nine documents were included. We identified ethical problem-solving models for occupational therapy and 16 ethical aspects in occupational therapy for cognitive deficits. The central theme of the analysis is the limited autonomy due to the consequences of the disease as well as the resulting tensions with those treating the patient.
Based on this systematic overview, it can neither be proven nor excluded with certainty that occupational therapy for cognitive impairment is an effective therapy for adult patients with central nervous system injuries compared to no occupational therapy. There is a lack of randomised trials with sufficient sample size, well-defined interventions, and comparable concomitant therapies in the control groups, but there is also a lack of well-designed observational studies in routine care and health economic studies. The identified systematic reviews on patient and social aspects provide information on the needs of patients after stroke or traumatic brain injury and their relatives, but there is a lack of studies on this aspect in German-speaking countries. For the ethical assessment, in addition to the identified theoretical models for solving ethical conflicts in occupational therapy, more empirical studies on ethical aspects with patients with cognitive deficits and their relatives as well as occupational therapists are needed.
PDF
