Mark Belger

Eli Lilly (United Kingdom)

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Catherine Reed

Eli Lilly (United States)

Josep María Haro

Parc Sanitari Sant Joan de Déu

Anders Wimo

Karolinska Institutet

Michael Happich

Eli Lilly (United Kingdom)

Roy Jones

The Research Institute for the Care of Older People

Richard Dodel

University of Duisburg-Essen

Bruno Vellas

Université de Toulouse

Alan Brnabic

Eli Lilly (United States)

Magali Sartral

Eli Lilly (United Kingdom)

Giuseppe Bruno

Sapienza University of Rome

Cooperative Institutions

Ibero American University

106

Eli Lilly (United States)

Eli Lilly (United Kingdom)

University of Oxford

Inserm

Karolinska Institutet

Eli Lilly (Germany)

Université Paris Cité

University College London

University of York

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

CO19 Sintilimab Plus Chemotherapy for First-Line Treatment of Advanced or Metastatic Nonsquamous Non-Small-Cell Lung Cancer (AMNSQNSCLC): A Systematic Literature Review (SLR) and Network Meta-Analysis (NMA)

Value in Health (2022)

M.C. Garassino ALAN J.M. BRNABIC Victoria Jennifer Stefaniak Mark Belger Kristi Gruver

Pemetrexed

Atezolizumab

Carboplatin

10.1016/j.jval.2022.04.117

Cite

Citations (0)

Reliability of coded data to identify earliest indications of cognitive decline, cognitive evaluation and Alzheimer’s disease diagnosis: a pilot study in England

BMJ Open (2018)

Grazia Dell’Agnello Urvi Desai Noam Y. Kirson Jody Wen Mark K. Meiselbach

Objectives Evaluate the reliability of using diagnosis codes and prescription data to identify the timing of symptomatic onset, cognitive assessment and diagnosis of Alzheimer’s disease (AD) among patients diagnosed with AD. Methods This was a retrospective cohort study using the UK Clinical Practice Research Datalink (CPRD). The study cohort consisted of a random sample of 50 patients with first AD diagnosis in 2010–2013. Additionally, patients were required to have a valid text-field code and a hospital episode or a referral in the 3 years before the first AD diagnosis. The earliest indications of cognitive impairment, cognitive assessment and AD diagnosis were identified using two approaches: (1) using an algorithm based on diagnostic codes and prescription drug information and (2) using information compiled from manual review of both text-based and coded data. The reliability of the code-based algorithm for identifying the earliest dates of the three measures described earlier was evaluated relative to the comprehensive second approach. Additionally, common cognitive assessments (with and without results) were described for both approaches. Results The two approaches identified the same first dates of cognitive symptoms in 33 (66%) of the 50 patients, first cognitive assessment in 29 (58%) patients and first AD diagnosis in 43 (86%) patients. Allowing for the dates from the two approaches to be within 30 days, the code-based algorithm’s success rates increased to 74%, 70% and 94%, respectively. Mini-Mental State Examination was the most commonly observed cognitive assessment in both approaches; however, of the 53 tests performed, only 19 results were observed in the coded data. Conclusions The code-based algorithm shows promise for identifying the first AD diagnosis. However, the reliability of using coded data to identify earliest indications of cognitive impairment and cognitive assessments is questionable. Additionally, CPRD is not a recommended data source to identify results of cognitive assessments.

Diagnosis code

Cognitive Decline

Cognitive test

10.1136/bmjopen-2017-019684

Cite

Citations (7)

Estimating the Economically Justifiable Price of Limited-Duration Treatment with Donanemab for Early Symptomatic Alzheimer’s Disease in the United States

Neurology and Therapy (2024)

Malaz Boustani Erin Doty Louis P. Garrison Lee Smolen Timothy Klein

The goal of this economic model is to estimate an economically justifiable price (EJP) for using donanemab for the treatment of early symptomatic Alzheimer's disease (AD) in the United States based on clinical data from the phase 3 TRAILBLAZER-ALZ 2 trial (NCT04437511).

10.1007/s40120-024-00649-y

Cite

Citations (0)

The MOPEAD project: Advancing patient engagement for the detection of “hidden” undiagnosed cases of Alzheimer's disease in the community

Alzheimer s & Dementia (2019)

Octavio Rodríguez‐Gómez Adrián Rodrigo Fátima Iradier Miguel A. Santos‐Santos H.P. Hundemer

Abstract In most, if not all health systems, dementia is underdiagnosed, and when diagnosis occurs, it is typically at a relatively late stage in the disease process despite mounting evidence showing that a timely diagnosis would result in numerous benefits for patients, families, and society. Moving toward earlier diagnoses in Alzheimer's disease (AD) requires a conscientious and collective effort to implement a global strategy addressing the multiple causes hindering patient engagement at different levels of society. This article describes the design of the Models of Patient Engagement for Alzheimer's Disease project, an ongoing EU‐funded public‐private multinational initiative that will compare four innovative patient engagement strategies across five European countries regarding their ability to identify individuals with prodromal AD and mild AD dementia, which are “hidden” in their communities and traditionally not found in the typical memory clinic setting. The strategies include an online AD citizen science platform, an open house initiative at the memory clinics, and patient engagement at primary care and diabetologist clinics.

Public Engagement

Memory clinic

Community Engagement

10.1016/j.jalz.2019.02.003

Cite

Citations (23)

Generalizability of clinical trial efficacy results to a real-world population: An example in migraine prevention

Journal of Managed Care & Specialty Pharmacy (2023)

M Paget Antje Tockhorn‐Heidenreich Mark Belger F. Chartier Michel Lantéri‐Minet

BACKGROUND: Health care decision makers are often concerned about the external validity of randomized controlled trials (RCTs), as their results may not apply to certain patients in the real world who intend to receive treatment. OBJECTIVE: To demonstrate a methodology for assessing the generalizability of clinical trial results to a real-world population, before sufficient and appropriate real-world effectiveness data are available, using individual patient-level data from an RCT and aggregated baseline data from a real-world French registry in migraine. METHODS: The analyses were conducted in 2 steps. First, individual patient-level baseline data from the multinational CONQUER RCT were weighted to match aggregated real-world InovPain registry patient characteristic data. Matched patient characteristics were sex, age, migraine type and duration, number of monthly migraine headache days, and number of monthly headache days at baseline. Second, the weighted CONQUER patient data were used to reanalyze the primary endpoint of CONQUER (least squares mean change from baseline in the number of monthly migraine headache days during the 3-month double-blind treatment phase) using predefined methodology. Sensitivity analyses were conducted to assess the robustness of findings. RESULTS: A total of 462 patients with migraine were randomized and treated with galcanezumab or placebo in CONQUER; aggregated InovPain data were available from 130 patients with migraine. We identified no important differences in baseline patient characteristics between the 2 prespecified populations, suggesting good external validity for CONQUER. Although this limited the extent of observed differences between the original and matched CONQUER populations, weighting of CONQUER data did help harmonize the 2 datasets and allow the results obtained in CONQUER to be generalized to patients more representative of the real-world French population with migraine. Results of weighted analyses suggested that galcanezumab would be superior to placebo for reducing monthly migraine headache days in a clinical trial in patients with episodic or chronic migraine who reflected the characteristics of patients eligible to receive the drug in France. CONCLUSIONS: Findings suggest that our methods may be helpful for assessing the generalizability of clinical trial results to a real-world population before the availability of substantial real-world clinical data.

External validity

10.18553/jmcp.2023.29.12.1321

Cite

Citations (0)

Olanzapine, risperidone or quetiapine treatment initiation: 12-month schizophrenia outpatient health outcomes (SOHO) study results

Diego Novick Josep María Haro Mark Belger S. Tzivelekis J Alonso

Quetiapine Fumarate

Source

Cite

Citations (0)

Inclusion Of Multiple Studies In Matching Adjusted Indirect Comparisons (Maic)

Value in Health (2015)

Mark Belger Alan Brnabic Zbigniew Kadziola Helmut Petto D Faries

Pooling

10.1016/j.jval.2015.03.196

Cite

Citations (10)

A risk scoring system to predict coronary stent thrombosis

Current Medical Research and Opinion (2017)

Nikesh Malik Amerjeet Banning Mark Belger Walid Fakhouri Peita Graham-Clarke

Objective: Stent thrombosis (ST) is a potentially life-threatening complication of percutaneous coronary intervention (PCI). We aimed to develop a scoring system to predict the risk of ST following PCI.Research design and methods: Odds ratios (ORs) for risk factors associated with ST were identified from a meta-analysis based on a systematic literature review, and through consensus expert opinion (Delphi–RAND method). The combined ORs were used to calculate risk scores for acute (within 24 hours), early (within 30 days) and late (31 days to 1 year) ST. Risk scores were validated against patient-level data from the TRITON-TIMI 38 study. Twenty risk factors were identified.Results: The most highly predictive factor for early and late ST was “incomplete duration of dual antiplatelet therapy”. Derived total risk scores ranged from 0 to 22 for acute and early ST, and from 0 to 20 for late ST. Increasing scores were associated with an increasing risk of ST when applied to trial data. Model discrimination was 0.60 (p = .0028), 0.67 (p < .0001) and 0.66 (p < .0001) for acute, early and late ST respectively, indicating good discriminatory power for predicting ST. Key limitations included a lack of published data on acute ST, resulting in a risk score for this time point being based predominantly on expert opinion, and that it was not possible to map all risk factors to variables collected in the TRITON-TIMI 38 study.Conclusion: Our weighted scoring system may help to stratify ST risk and individualize antiplatelet therapy in patients undergoing PCI.

Coronary stent

10.1080/03007995.2017.1292680

Cite

Citations (6)

Assessing the Cost-effectiveness of a Hypothetical Disease-modifying Therapy With Limited Duration for the Treatment of Early Symptomatic Alzheimer Disease

Clinical Therapeutics (2022)

Malaz Boustani Erin Doty Louis P. Garrison Lee Smolen Mark Belger

Clinical trials have produced promising results for disease-modifying therapies (DMTs) for Alzheimer's disease (AD); however, the evidence on their potential cost-effectiveness is limited. This study assesses the cost-effectiveness of a hypothetical DMT with a limited treatment duration in AD.We developed a Markov state-transition model to estimate the cost-effectiveness of a hypothetical DMT plus best supportive care (BSC) versus BSC alone among Americans living with mild cognitive impairment (MCI) due to AD or mild AD. AD states included MCI due to AD, mild AD, moderate AD, severe AD, and death. A hypothetical DMT was assumed to confer a 30% reduction in progression from MCI and mild AD. The base case annual drug acquisition cost was assumed to be $56,000. Other medical and indirect costs were obtained from published literature or list prices. Utilities for patients and caregivers were obtained from the published literature and varied by AD state and care setting (community care or long-term care). We considered 3 DMT treatment strategies: (1) treatment administered until patients reached severe AD (continuous strategy), (2) treatment administered for a maximum duration of 18 months or when patients reached severe AD (fixed-duration strategy), and (3) 40% of patients discontinuing treatment at 6 months because of amyloid plaque clearance and the remaining patients continuing treatment until 18 months or until they reached severe AD (test-and-discontinue strategy). Incremental cost-effectiveness ratios (ICERs) were calculated as the incremental cost per quality-adjusted life-year (QALY) gained.From the health care sector perspective, continuous treatment with a hypothetical DMT versus BSC resulted in an ICER of $612,354 per QALY gained. The ICER decreased to $157,288 per QALY gained in the fixed-duration strategy, driven by large reductions in treatment costs. With 40% of patients discontinuing treatment at 6 months (test-and-discontinue strategy), the ICER was $125,631 per QALY gained. In sensitivity and scenario analyses, the ICER was the most sensitive to changes in treatment efficacy, treatment cost, and the initial population AD state distribution. From the modified societal perspective, ICERs were 6.3%, 20.4%, and 25.1% lower than those from the health care sector perspective for the continuous, fixed-duration, and test-and-discontinue strategies, respectively.Under a set of assumptions for annual treatment costs and the magnitude and duration of treatment efficacy, DMTs used for a limited duration may deliver value consistent with accepted US cost-effectiveness thresholds.

10.1016/j.clinthera.2022.09.008

Cite

Citations (13)

The “RCT augmentation”: a novel simulation method to add patient heterogeneity into phase III trials

BMC Medical Research Methodology (2018)

Hélène Karcher Shuai Fu Jie Meng Mikkel Zöllner Ankarfeldt Orestis Efthimiou

Phase III randomized controlled trials (RCT) typically exclude certain patient subgroups, thereby potentially jeopardizing estimation of a drug’s effects when prescribed to wider populations and under routine care (“effectiveness”). Conversely, enrolling heterogeneous populations in RCTs can increase endpoint variability and compromise detection of a drug’s effect. We developed the “RCT augmentation” method to quantitatively support RCT design in the identification of exclusion criteria to relax to address both of these considerations. In the present manuscript, we describe the method and a case study in schizophrenia. We applied typical RCT exclusion criteria in a real-world dataset (cohort) of schizophrenia patients to define the “RCT population” subgroup, and assessed the impact of re-including each of the following patient subgroups: (1) illness duration 1–3 years; (2) suicide attempt; (3) alcohol abuse; (4) substance abuse; and (5) private practice management. Predictive models were built using data from different “augmented RCT populations” (i.e., subgroups where patients with one or two of such characteristics were re-included) to estimate the absolute effectiveness of the two most prevalent antipsychotics against real-world results from the entire cohort. Concurrently, the impact on RCT results of relaxing exclusion criteria was evaluated by calculating the comparative efficacy of those two antipsychotics in virtual RCTs drawing on different “augmented RCT populations”. Data from the “RCT population”, which was defined with typical exclusion criteria, allowed for a prediction of effectiveness with a bias < 2% and mean squared error (MSE) = 5.8–6.8%. Compared to this typical RCT, RCTs using augmented populations provided improved effectiveness predictions (bias < 2%, MSE = 5.3–6.7%), while returning more variable comparative effects. The impact of augmentation depended on the exclusion criterion relaxed. Furthermore, half of the benefit of relaxing each criterion was gained from re-including the first 10–20% of patients with the corresponding real-world characteristic. Simulating the inclusion of real-world subpopulations into an RCT before running it allows for quantification of the impact of each re-inclusion upon effect detection (statistical power) and generalizability of trial results, thereby explicating this trade-off and enabling a controlled increase in population heterogeneity in the RCT design.

10.1186/s12874-018-0534-6

Cite

Citations (2)