Article
Pharmacology & Pharmacy
Carolin Herrmann, Corinna Kluge, Maximilian Pilz, Meinhard Kieser, Geraldine Rauch
Summary: Sample size calculations in clinical trials need to be carefully considered based on parameter assumptions. Adaptive group sequential study designs offer a solution to planning uncertainties by allowing for updates to sample sizes based on observed interim effects. Incorporating resampling elements in sample size recalculation approaches can result in smoother rules and lower variability in sample sizes, leading to substantial performance improvements compared to previous methods.
PHARMACEUTICAL STATISTICS
(2021)
Article
Medicine, Research & Experimental
Thomas Perneger, Christophe Combescure, Antoine Poncet
Summary: Baseline prognostic factors in randomized clinical trials are usually adjusted using sample-based regression models, which may be incorrect due to overfitting. To assess this issue, we conducted a simulation study comparing sample-based adjustment with true adjustment in estimating treatment effects.
Article
Health Care Sciences & Services
Amra Hot, Norbert Benda, Patrick M. Bossuyt, Oke Gerke, Werner Vach, Antonia Zapf
Summary: This study introduces an adaptive design with blinded sample size recalculation to enhance the possibility of success in clinical trials. Through simulation studies, it was found that the adaptive design achieves the desired theoretical power.
BMC MEDICAL RESEARCH METHODOLOGY
(2022)
Article
Mathematical & Computational Biology
Steven Teerenstra, Jessica Kasza, Ruslan Leontjevas, Andrew B. Forbes
Summary: In randomized controlled trials, treatment-related clustering at follow-up can lead to correlated outcomes among different subjects. Adjusting for baseline measure in the analysis can reduce sample size requirements. We provide sample size formulas for various designs and investigate small sample properties.
STATISTICS IN MEDICINE
(2023)
Article
Multidisciplinary Sciences
Ben O'Neill
Summary: This article analyzes standard confidence intervals for the mean of a finite population and proposes a new method for sample size determination that takes into account the uncertainty of the parameter. By using a preliminary sample of data, this method increases the accuracy of inference.
Article
Surgery
David Chadow, N. Bryce Robinson, Gianmarco Cancelli, Giovanni Soletti, Katia Audisio, Mohamed Rahouma, Roberto Perezgrovas, Mario Gaudino
Summary: It is estimated that 25-30% of randomized controlled trials fail to reach their target sample size. Factors such as multicentre design, publication year, and commercial sponsor are inversely associated with failure to reach the target sample size. A substantial proportion of surgical trials fail to reach the target sample size, but there is an improving trend.
BRITISH JOURNAL OF SURGERY
(2022)
Article
Mathematical & Computational Biology
Yaru Shi, Fang Liu, Se Li, Jie Chen
Summary: This article introduces five new approaches to address the issue of low power in confirmatory randomized controlled trials when variability and/or effect size estimated from small-scale pilot studies are not taken into account in the sample size calculation. These new methods encompass different statistical approaches and are compared through simulations.
STATISTICS IN BIOPHARMACEUTICAL RESEARCH
(2021)
Article
Mathematics, Interdisciplinary Applications
Gerard J. P. Van Breukelen
Summary: Cluster randomized trials assign clusters of persons to treatments, and all persons in the same cluster receive the same treatment. This paper demonstrates the equivalence of four analysis methods for cluster randomized trials with a pretest and post-test of a quantitative outcome. It also introduces a simple method to calculate the sample size for a cluster randomized trial with baseline measurement.
MULTIVARIATE BEHAVIORAL RESEARCH
(2023)
Article
Health Care Sciences & Services
Mark J. Bolland, Greg D. Gamble, Alison Avenell, David J. Cooper, Andrew Grey
Summary: This study investigated the application of comparing observed and expected distributions of baseline categorical variables in randomized controlled trials (RCTs). The findings revealed discrepancies between the observed and expected distributions in trials with publication integrity concerns, as well as differences between reported and calculated P-values. These indicators can be used to assess the publication integrity of a body of RCTs.
JOURNAL OF CLINICAL EPIDEMIOLOGY
(2023)
Article
Mathematical & Computational Biology
Satoshi Hattori, Sho Komukai, Tim Friede
Summary: In randomized clinical trials, incorporating baseline covariates can improve the power in hypothesis testing for treatment effects. The Cox proportional hazards model with baseline covariates as explanatory variables can improve the standard logrank test. We propose a simple strategy for sizing randomized clinical trials utilizing historical data and derive a power formula for the augmented logrank test.
STATISTICS IN MEDICINE
(2022)
Article
Public, Environmental & Occupational Health
Yongdong Ouyang, Fan Li, John S. Preisser, Monica Taljaard
Summary: There has been a surge of interest in stepped-wedge cluster randomized trials (SW-CRTs) in recent years, leading to the rapid development of methodologies and various power and sample size calculation software. Researchers can benefit from reviewing and understanding the features of existing calculators to choose the most appropriate one for their trials, ultimately improving the accuracy of sample size and power calculations.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2022)
Article
Mathematical & Computational Biology
Peijin Wang, Shein-Chung Chow
Summary: This article discusses methods for sample size re-estimation in clinical trials, including the adjusted effect size (AES) approach and the iterated expectation/variance (IEV) approach, which take into account the variability of observed responses. Results show that the IEV approach generally performs best in controlling type I error inflation, but may lead to a larger increase in sample size when detecting smaller effect sizes.
STATISTICS IN MEDICINE
(2021)
Article
Health Care Sciences & Services
Jijia Wang, Jing Cao, Song Zhang, Chul Ahn
Summary: The study presents a closed-form sample size calculation method based on the GEE approach, applicable to stepped-wedge design in pragmatic trials. The proposed method is flexible in addressing design issues commonly encountered in pragmatic trials, including different correlation structures, irregular crossover schedules, and missing data. Researchers can analytically assess the impact of different design factors on sample size requirement using the closed-form formulas.
STATISTICAL METHODS IN MEDICAL RESEARCH
(2021)
Review
Clinical Neurology
Mayank Goyal, Rosalie McDonough, Marc Fisher, Johanna Ospel
Summary: Randomized controlled trials (RCT) are important for evidence-based acute stroke care. While methods to assess statistical significance are standardized, there is no clear consensus on how to assess clinical significance. The minimal clinically important difference (MCID) is often used to describe the smallest change in outcomes that is considered meaningful to patients and leads to a change in patient management.
Article
Nutrition & Dietetics
Christian Ritz
Summary: This tutorial provides a detailed introduction to the statistical analysis of parallel-arm RCTs in nutrition, focusing on how trial design and other factors may influence subsequent statistical analysis. It covers all steps of the statistical analysis and includes a practical example.
EUROPEAN JOURNAL OF CLINICAL NUTRITION
(2021)
Article
Economics
Sebastian Jobjoernsson, Henning Schaak, Oliver Musshoff, Tim Friede
Summary: This paper discusses the important issue of ensuring sufficient power to reject hypotheses in economic experiments and introduces methods for testing multiple hypotheses simultaneously in adaptive, two-stage designs to improve experiment power. The paper provides a concise overview of relevant theory and demonstrates the method in three different applications, including a simulation study and analysis of previous experiment data sets. Simulation results highlight the potential for reducing sample sizes while maintaining the power to reject at least one hypothesis and controlling the overall Type I error probability.
EXPERIMENTAL ECONOMICS
(2023)
Review
Health Care Sciences & Services
Sarah Friedrich, Andreas Groll, Katja Ickstadt, Thomas Kneib, Markus Pauly, Joerg Rahnenfuhrer, Tim Friede
Summary: This article reviews regularization approaches in data science for overcoming overfitting and improving prediction, and discusses their limited application in medical research. The authors suggest increased use of regularization approaches in medicine, despite the added complexity they bring to analyses. Proper investments in computing facilities and educational resources can help overcome these challenges.
STATISTICAL METHODS IN MEDICAL RESEARCH
(2023)
Article
Geriatrics & Gerontology
Ana Mazur, Britta Tetzlaff, Tina Mallon, Berit Hesjedal-Streller, Vivien Weiss, Martin Scherer, Sascha Koepke, Katrin Balzer, Linda Steyer, Tim Friede, Sebastian Pfeiffer, Eva Hummers, Christiane Mueller
Summary: To improve collaboration between general practitioners and nurses in nursing homes, researchers developed an intervention package called interprof ACT. However, the implementation of this intervention did not have a significant impact on hospitalisation rates and other clinical parameters among nursing home residents.
Article
Mathematical & Computational Biology
Sarah Friedrich, Tim Friede
Summary: Method comparisons are important for applied researchers to make informed choices. This paper investigates different approaches to comparison and aims to develop new methods by combining the advantages of these approaches.
BIOMETRICAL JOURNAL
(2023)
Article
Mathematical & Computational Biology
Roland G. G. Gera, Tim Friede
Summary: The increasing interest in subpopulation analysis in personalized medicine and targeted therapies has led to the development of various new trial designs and analysis methods. This paper proposes a trial design applicable to any set of composite populations and considers normally distributed endpoints and random baseline covariates. The study uses p-values calculated on subset levels and the inverse normal combination function to test treatment effects for composite populations, while also accounting for multiple testing using the closed testing procedure. The paper also derives critical boundaries for intersection hypothesis tests and provides simulations demonstrating the absence of practical relevant inflation of the type I error rate. The target power after sample size recalculation is typically met or close to being met.
BIOMETRICAL JOURNAL
(2023)
Book Review
Mathematical & Computational Biology
Tim Friede
BIOMETRICAL JOURNAL
(2023)
Article
Cardiac & Cardiovascular Systems
Julia Hoffmann, Sabine Hanss, Monika Kraus, Jens Schaller, Christian Schaefer, Dana Stahl, Stefan D. Anker, Gabriele Anton, Thomas Bahls, Stefan Blankenberg, Arne Blumentritt, Leif-Hendrik Boldt, Steffen Cordes, Steffen Desch, Wolfram Doehner, Marcus Doerr, Frank Edelmann, Ingo Eitel, Matthias Endres, Stefan Engelhardt, Jeanette Erdmann, Katharina Eulenburg, Volkmar Falk, Stephan B. Felix, Derk Frank, Thomas Franke, Norbert Frey, Tim Friede, Lars Geidel, Lisa Germans, Ulrich Grabmaier, Martin Halle, Joerg Hausleiter, Vera Jakobi, Ahmad-Fawad Jebran, Alexander Jobs, Stefan Kaeaeb, Mahir Karakas, Hugo A. Katus, Alexandra Klatt, Christoph Knosalla, Joachim Krebser, Ulf Landmesser, Mahsa Lee, Kristin Lehnert, Stephanie Lesser, Katrin Leyh, Roberto Lorbeer, Stephanie Mach-Kolb, Benjamin Meder, Eike Nagel, Christian H. Nolte, Abdul S. Parwani, Astrid Petersmann, Miriam Puls, Henriette Rau, Maximilian Reiser, Otto Rienhoff, Tabea Scharfe, Mario Schattschneider, Heiko Scheel, Renate B. Schnabel, Andreas Schuster, Boris Schmitt, Tim Seidler, Moritz Seiffert, Barbara-Elisabeth Staehli, Adriane Stas, Thomas J. Stocker, Lukas von Stuelpnagel, Holger Thiele, Rolf Wachter, Reza Wakili, Tanja Weis, Kerstin Weitmann, Heinz-Erich Wichmann, Philipp Wild, Tanja Zeller, Wolfgang Hoffmann, Elisabeth Maria Zeisberg, Wolfram-Hubertus Zimmermann, Dagmar Krefting, Titus Kuehne, Annette Peters, Gerd Hasenfuss, Steffen Massberg, Thomas Sommer, Stefanie Dimmeler, Thomas Eschenhagen, Matthias Nauck
Summary: The German Centre for Cardiovascular Research (DZHK) aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics for people with cardiovascular disease. The DZHK designed a research platform to standardize data and sample collections across all studies and ensure compliance with legal regulations and FAIR principles. The platform includes web-based and central units for data management, as well as a Public Open Data strategy to enable interdisciplinary use of data and samples.
CLINICAL RESEARCH IN CARDIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Stefan D. Anker, Muhammad Shahzeb Khan, Javed Butler, Stephan von Haehling, Ewa A. Jankowska, Piotr Ponikowski, Tim Friede
Summary: Iron deficiency is common in patients with heart failure and reduced ejection fraction, and it is associated with a poor prognosis. The effect of intravenous iron replacement on recurrent heart failure hospitalizations and cardiovascular mortality in these patients is uncertain. This study used a Bayesian analysis to provide precise estimates of the effect of intravenous iron replacement and found that it significantly reduced the rates of recurrent heart failure hospitalizations and cardiovascular mortality.
EUROPEAN JOURNAL OF HEART FAILURE
(2023)
Article
Geriatrics & Gerontology
Markus S. Anker, Alessia Lena, Eric J. Roeland, Jan Porthun, Sebastian Schmitz, Sara Hadzibegovic, Philipp Sikorski, Ursula Wilkenshoff, Ann-Kathrin Froehlich, Luisa Valentina Ramer, Matthias Rose, Jan Eucker, Tienush Rassaf, Matthias Totzeck, Lorenz H. Lehmann, Stephan von Haehling, Andrew J. S. Coats, Tim Friede, Javed Butler, Stefan D. Anker, Hanno Riess, Ulf Landmesser, Lars Bullinger, Ulrich Keller, Johann Ahn
Summary: The patient-reported ability to walk 4 m and wash oneself is an independent predictor of survival and associated with decreased functional status in pre-terminal cancer patients.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Mathematical & Computational Biology
Eric S. Knop, Markus Pauly, Tim Friede, Thilo Welz
Summary: Analysts often overlook interaction terms in meta-regression models, which may result in biased conclusions. We demonstrate this through a reanalysis of a meta-regression study on acute heart failure. With a total of 285 studies, we examine the 1-year mortality rate and its association with study-level factors such as recruitment year and average age. Our findings highlight the importance of including possible confounders and interaction terms in mixed-effects meta-regression models to avoid erroneous inference.
RESEARCH SYNTHESIS METHODS
(2023)
Article
Cardiac & Cardiovascular Systems
Christine Zelenak, Jonas Nagel, Kristina Bersch, Lisa Derendorf, Frank Doyle, Tim Friede, Birgit Herbeck Belnap, Sebastian Kohlmann, Soren T. Skou, Carlos A. Velasco, Christian Albus, Thomas Asendorf, Christian Axel Bang, Margarita Beresnevaite, Niels Eske Bruun, Matthew M. Burg, Sussi Friis Buhl, Peter H. Gaede, Dagmar Luehmann, Anna Markser, Klaudia Vivien Nagy, Chiara Rafanelli, Sanne Rasmussen, Jens Sondergaard, Jan Sorensen, Adrienne Stauder, Stephanie Stock, Stefano Urbinati, Diego Della Riva, Rolf Wachter, Florian Walker, Susanne S. Pedersen, Christoph Herrmann-Lingen
Summary: This article presents a comprehensive study to evaluate the impact of an integrated care model based on a collaborative approach and information and communication technologies on health-related quality of life and disease outcomes in elderly patients with multiple morbidities. If proven effective, this integrated care model can be implemented in routine care for older patients with multiple morbidities across participating countries and beyond.
Article
Cardiac & Cardiovascular Systems
Piotr Ponikowski, Robert J. Mentz, Adrian F. Hernandez, Javed Butler, Muhammad Shahzeb Khan, Dirk J. van Veldhuisen, Bernard Roubert, Nicole Blackman, Tim Friede, Ewa A. Jankowska, Stefan D. Anker
Summary: This meta-analysis of intravenous ferric carboxymaltose therapy for iron-deficient heart failure patients found a significantly reduced risk of hospitalizations for HF and cardiovascular causes, with no apparent effect on mortality.
EUROPEAN HEART JOURNAL
(2023)
Article
Clinical Neurology
Nicole Krause, Carlotta Derad, Barbara von Glasenapp, Karin Riemann-Lorenz, Herbert Temmes, Markus van de Loo, Tim Friede, Thomas Asendorf, Christoph Heesen
Summary: The study investigated the health behaviors and disease characteristics of newly diagnosed MS patients in Germany and found associations between these aspects. The results showed that the majority of participants had unhealthy lifestyle habits, such as smoking, obesity, and lack of physical activity. Higher disease severity scores were associated with higher lesion burden and relapse rates, while smoking was associated with higher lesion burden and unhealthy dietary habits. Higher disease severity scores and BMI were associated with lower quality of life. Additionally, lower quality of life was associated with a desire to optimize stress management, physical activity, and sleep behavior.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2023)
Article
Mathematical & Computational Biology
Matthias Schmid, Tim Friede, Nadja Klein, Leonie Weinhold
Summary: In recent years, new scoring tools for disease prognosis and prediction have been developed. However, these tools need to be validated on external data before being used in clinical applications. The validation process is often challenging due to logistical issues, resulting in multiple small-sized validation studies. This article focuses on strategies for meta-analyzing the concordance probability (C-index) for time-to-event data, and proposes methods for incorporating time as a covariate in the meta-regression model equation.
RESEARCH SYNTHESIS METHODS
(2023)
Article
Health Care Sciences & Services
Louisa -Kristin Muntendorf, Katrin Balzer, Tim Friede, Eva Hummers, Hans-helmut Koenig, Christiane Mueller, Martin Scherer, Linda Steyer, Britta Tetzlaff, Sebastian Pfeiffer, Alexander Konnopka, The Interprof Act Consortium
Summary: The German trial interprof ACT aimed to improve inter-professional collaboration between nursing home staff and local general practitioners. However, the interventions were found to be not cost-effective compared to the current standard of care.
INTERNATIONAL JOURNAL OF INTEGRATED CARE
(2023)