Article 6. an Introduction to Hypothesis Testing. Parametric Comparison of Two Groups—1

Total Page:16

File Type:pdf, Size:1020Kb

Article 6. an Introduction to Hypothesis Testing. Parametric Comparison of Two Groups—1 124 Emerg Med J 2001;18:124–130 AN INTRODUCTION TO STATISTICS Emerg Med J: first published as 10.1136/emj.18.2.124 on 1 March 2001. Downloaded from Article 6. An introduction to hypothesis testing. Parametric comparison of two groups—1 P Driscoll, F Lecky Objectives Table 1 Types of test of significance for two group x Dealing with paired parametric data comparison x Comparing confidence intervals and p Parametric Non-parametric values In covering these objectives the following terms Quantitative Nominal z test ÷2 test will be introduced: Paired Fisher exact test x Parametric and non-parametric analysis Independent Ordinal x Paired z test t test Wilcoxon rank sum test Paired Mann-Whitney x Paired t test Independent Kolmogorov-Smirnov We have shown previously that statistical infer- ence enables general conclusions to be drawn from specific data. For example estimating a distribution of a population these features are population’s mean from a sample mean. At known as parameters. Parametric analysis relies first glance this may not appear important. In on the data being normally (or nearly) distrib- practice however the ability to make these esti- uted so that an estimation of the underlying 3 mations is fundamental to most medical inves- population’s parameters can be made. These tigations. These tend to concentrate on dealing can then be used to test the null hypothesis. As with one or more of the following questions: only quantitative data can have a normal distri- Have the observations changed with time bution, it follows that parametric analysis can and/or intervention? only be used on quantitative data (table 1). Do two or more groups of observations http://emj.bmj.com/ diVer from each other? Key point Is there an association between diVerent All parametric tests use quantitative data observations? but not all quantitative data have to be ana- To answer these questions many diVerent lysed using parametric tests. types of statistical inference tests have been developed to deal with varying sample sizes and diVerent types of data. Though the tests NON-PARAMETRIC ANALYSIS diVer they have the common aim of assessing These tests of the null hypothesis do not on September 27, 2021 by guest. Protected copyright. whether the null hypothesis is likely to be cor- assume any particular distribution for the data. rect (box 1). They are known collectively as Instead they look at the category or rank order “tests of significance”.1 of the values and ignore the absolute diVerence between them. Consequently non-parametric analysis is used on nominal and ordinal data as Box 1 The null hypothesis well as quantitative data that are not normally There is no diVerence between the groups (or nearly normally) distributed (table 1). with respect to the measurement made. IfadiVerence exists between the study groups, it is more likely to be found using para- metric tests. It is therefore important to know The significance test chosen is dependent upon for certain if the data are normally distributed. the type of data we are dealing with, whether it You can sometimes determine this by checking has a normal distribution and the type of ques- the distribution curve of the plotted data. A tion being asked.2 Once the distribution of the more formal way is to use a computer to show data is known, you can tell if the null how precisely the data fit with a normal distri- hypothesis should be tested using parametric Accident and bution. This will be described in greater detail or non-parametric methods. Emergency in the next article. When data are not normally Department, Hope distributed attempts are often made to trans- Hospital, Salford M6 8HD, UK Parametric and non-parametric analysis form it so that parametric analysis can be car- PARAMETRIC ANALYSIS ried out. The commonest method used is loga- Correspondence to: A normal distribution is a regular shape. As such rithmic transformation.2 This has the added Mr Driscoll, Consultant in it is possible to draw the curve exactly by simply advantage of allowing geometric means and Accident and Emergency Medicine (pdriscoll@ knowing the mean, standard deviation and vari- confidence intervals to be calculated that have hope.srht.nwest.nhs.uk) ance of the data. When considering a normal the same units as the original data. www.emjonline.com An introduction to hypothesis testing 125 approximately normally distributed.4 As this is Key points often the case the paired t test, rather than its z Emerg Med J: first published as 10.1136/emj.18.2.124 on 1 March 2001. Downloaded from x Non-parametric analysis can be used on counterpart, is more commonly seen in the any data but parametric analysis can only medical literature. To show how these tests are be used when the data are normally applied consider the following examples. distributed. x Provided they are appropriately used, parametric tests derive more information PAIRED Z TEST about the whole population than non- Dr Egbert Everard continues to work in the parametric ones. Emergency Department of Deathstar General. His consultant, Dr Canute, asks him to find out if Neverwheeze, the new bronchodilator for Having determined that parametric analysis is asthmatics, significantly changes patient’s peak appropriate you then need to select the best flow rate (PFR). To do this he follows the sys- statistical test. This depends upon the size of tematic approach described in box 2. the samples and the type of question being asked. In all cases however the following 1 State the null hypothesis and alternative systematic approach is used (box 2). hypothesis of the study Having considered the problem, Egbert writes Box 2 System for statistical down the null hypothesis as: comparison of two groups “There is no diVerence in asthmatic patient’s x State the null hypothesis and the alterna- PFR before and after receiving Never- tive hypothesis of the study wheeze”. x Select the level of significance This can be summarised to: x Establish the critical values Mean diVerence in PFR = 0 x Select a sample and calculate its mean The alternative hypothesis is the logical oppo- and standard error of the mean (SEM)* site of this, that is: x Calculate the test statistic “There is a diVerence in asthmatic patient’s x Compare the calculated test statistic with PFR before and after receiving Never- the critical values wheeze”. x Express the chances of obtaining results This can be summarised to: ≠ at least this extreme if the null hypothesis Mean diVerence in PFR 0 is true *or estimated standard error of the mean 2 Select the level of significance (ESEM) if using a sample size < 100.4 If the null hypothesis is correct the PFR before and after Neverwheeze should be the same. However, even if this were true it would be very unlikely they would be exactly the same http://emj.bmj.com/ Paired or independent parametric because of random variation between patients. analysis You would expect some PFR to increase and Two types of parametric statistical tests can be others to fall. Overall however the mean diVer- used to compare the means of two study groups. ence between the two groups should be zero if The choice depends upon whether the data you the null hypothesis is valid. are dealing with are independent or paired. When groups are widely separated it is likely Data can be considered to be paired when that the null hypothesis is not valid. For exam- two related observations are taken with analysis ple, if 100 people died in your department one on September 27, 2021 by guest. Protected copyright. concentrating on the diVerence between the day and none the next then its highly unlikely paired scores. Examples of these type of data that a diVerence this big would be attributable include: to chance. In contrast you would be less confi- x “Before” and “after” studies carried out on dent to rule out the eVect of chance if the dif- the same subjects ference in death rate was only 1. The question x Observations made on individually matched therefore is how big does the diVerence need to pairs where only the factor under investiga- be before the null hypothesis can be rejected? tion is diVerent Rather than guessing, it is better to consider Independent data are when the subjects for what values are possible. If we measured the the two groups are picked at random such that mean PFR diVerence in groups of asthmatic selection for one group will not eVect the sub- patients selected randomly we would find the jects chosen for the other. The tests used to sample means form a normal distribution analyse these data will be discussed in the next around the population’s mean diVerence. As it article. For now we will concentrate on paired is a normal distribution it is possible to convert data. this to a standard normal distribution.5 The probability of getting a particular sample mean PAIRED TESTS can then be read from the table of z statistics Both z and t tests can be used to investigate the where: diVerence between the means of two sets of z = [sample mean diVerence −population paired observations. The former is, however, mean diVerence (µ)]/standard error of the only valid if the samples are suYciently large.4 mean (SEM) When this is not the case we can use the t sta- Where: tistic provided that the population of the mean SEM = population standard deviation (ó)/ diVerences in scores between the pairs is 'number in the sample (n) www.emjonline.com 126 Driscoll, Lecky selected. The z statistic derived from the sam- In this case we do not know the value of ó.
Recommended publications
  • The Statistical Significance of Randomized Controlled Trial Results Is Frequently Fragile: a Case for a Fragility Index
    The statistical significance of randomized controlled trial results is frequently fragile: A case for a Fragility Index Walsh, M., Srinathan, S. K., McAuley, D. F., Mrkobrada, M., Levine, O., Ribic, C., Molnar, A. O., Dattani, N. D., Burke, A., Guyatt, G., Thabane, L., Walter, S. D., Pogue, J., & Devereaux, P. J. (2014). The statistical significance of randomized controlled trial results is frequently fragile: A case for a Fragility Index. Journal of Clinical Epidemiology, 67(6), 622-628. https://doi.org/10.1016/j.jclinepi.2013.10.019 Published in: Journal of Clinical Epidemiology Document Version: Publisher's PDF, also known as Version of record Queen's University Belfast - Research Portal: Link to publication record in Queen's University Belfast Research Portal Publisher rights 2014 The Authors. Published by Elsevier Inc. This is an open access article published under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/3.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited. General rights Copyright for the publications made accessible via the Queen's University Belfast Research Portal is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The Research Portal is Queen's institutional repository that provides access to Queen's research output. Every effort has been made to ensure that content in the Research Portal does not infringe any person's rights, or applicable UK laws.
    [Show full text]
  • Why Do You Need a Biostatistician? Antonia Zapf1* , Geraldine Rauch2 and Meinhard Kieser3
    Zapf et al. BMC Medical Research Methodology (2020) 20:23 https://doi.org/10.1186/s12874-020-0916-4 DEBATE Open Access Why do you need a biostatistician? Antonia Zapf1* , Geraldine Rauch2 and Meinhard Kieser3 Abstract The quality of medical research importantly depends, among other aspects, on a valid statistical planning of the study, analysis of the data, and reporting of the results, which is usually guaranteed by a biostatistician. However, there are several related professions next to the biostatistician, for example epidemiologists, medical informaticians and bioinformaticians. For medical experts, it is often not clear what the differences between these professions are and how the specific role of a biostatistician can be described. For physicians involved in medical research, this is problematic because false expectations often lead to frustration on both sides. Therefore, the aim of this article is to outline the tasks and responsibilities of biostatisticians in clinical trials as well as in other fields of application in medical research. Keywords: Medical research, Biostatistician, Tasks, Responsibilities Background Biometric Society (IBS) provides a definition of biomet- What is a biostatistician, what does he or she actually do rics as a ‘field of development of statistical and mathem- and what distinguishes him or her from, for example, an atical methods applicable in the biological sciences’ [2]. epidemiologist? If we would ask this our main cooper- In here, we will focus on (human) medicine as area of ation partners like physicians or biologists, they probably application, but the results can be easily transferred to could not give a satisfying answer. This is problematic the other biological sciences like, for example, agricul- because false expectations often lead to frustration on ture or ecology.
    [Show full text]
  • Medical Statistics PDF File 9
    M249 Practical modern statistics Medical statistics About this module M249 Practical modern statistics uses the software packages IBM SPSS Statistics (SPSS Inc.) and WinBUGS, and other software. This software is provided as part of the module, and its use is covered in the Introduction to statistical modelling and in the four computer books associated with Books 1 to 4. This publication forms part of an Open University module. Details of this and other Open University modules can be obtained from the Student Registration and Enquiry Service, The Open University, PO Box 197, Milton Keynes MK7 6BJ, United Kingdom (tel. +44 (0)845 300 60 90; email [email protected]). Alternatively, you may visit the Open University website at www.open.ac.uk where you can learn more about the wide range of modules and packs offered at all levels by The Open University. To purchase a selection of Open University materials visit www.ouw.co.uk, or contact Open University Worldwide, Walton Hall, Milton Keynes MK7 6AA, United Kingdom for a brochure (tel. +44 (0)1908 858779; fax +44 (0)1908 858787; email [email protected]). Note to reader Mathematical/statistical content at the Open University is usually provided to students in printed books, with PDFs of the same online. This format ensures that mathematical notation is presented accurately and clearly. The PDF of this extract thus shows the content exactly as it would be seen by an Open University student. Please note that the PDF may contain references to other parts of the module and/or to software or audio-visual components of the module.
    [Show full text]
  • The Use of Stata in Medical Statistics and Epidemiology: a Long Journey
    A retrospective view Stata Progress Epidemiology and Biostatistics with Stata My Journey with Stata The use of Stata in Medical Statistics and Epidemiology: a long journey Rino Bellocco, Sc.D. Department of Statistics and Quantitative Methods University of Milano-Bicocca & Department of Medical Epidemiology and Biostatistics Karolinska Institutet Nordic and Baltic Stata Users Group meeting, Stockholm, September 1, 2017 1 / 44 A retrospective view Stata Progress Epidemiology and Biostatistics with Stata My Journey with Stata Outline A retrospective view Stata Progress Epidemiology and Biostatistics with Stata My Journey with Stata 2 / 44 A retrospective view Stata Progress Epidemiology and Biostatistics with Stata My Journey with Stata Outline A retrospective view Stata Progress Epidemiology and Biostatistics with Stata My Journey with Stata 3 / 44 A retrospective view Stata Progress Epidemiology and Biostatistics with Stata My Journey with Stata Some History 1985-1995 • Version 1.0 - 1.5, January 1985 - February 1987 (around 48 commands, regress logit ) 4 / 44 N. J. Cox 15 Table 2: Releases of Stata 1.0 January 1985 3.1 August 1993 1.1 February 1985 4.0 January 1995 1.2 March 1985 5.0 October 1996 1.4 August 1986 6.0 January 1999 1.5 February 1987 7.0 December 2000 2.0 June 1988 8.0 January 2003 A retrospective view Stata2.05 Progress June 1989Epidemiology and Biostatistics8.1 July with 2003 Stata My Journey with Stata 2.1 September 1990 8.2 October 2003 3.0 MarchBasic 1992 Commands Table 3: Stata 1.0 and Stata 1.1 append dir infile plot spool beep do input query summarize by drop label regress tabulate capture erase list rename test confirm exit macro replace type convert expand merge run use correlate format modify save count generate more set describe help outfile sort Stata 1.0 had int, long, float,anddouble variables; it did not have byte or str#.
    [Show full text]
  • Medical Statistics Made Easy Medical Statistics Made Easy M
    MEDICAL STATISTICS MADE EASY STATISTICS MEDICAL MEDICAL STATISTICS MADE EASY M. HARRIS and G. TAYLOR 4th EDITION HARRIS and TAYLOR 4 MEDICAL STATISTICS MADE EASY 4 MSME_Book.indb 1 17/08/2020 12:10 MSME_4e_234x156_Prelims.indd 1 06/05/2020 16:02 MEDICAL STATISTICS MADE EASY 4 Michael Harris Professor of Primary Care and former General Practitioner, Bath, UK and Gordon Taylor Professor of Medical Statistics, College of Medicine and Health, University of Exeter, UK MSME_Book.indb 3 17/08/2020 12:10 MSME_4e_234x156_Prelims.indd 3 06/05/2020 16:02 Fourth edition © Scion Publishing Ltd, 2021 ISBN 978 1 911510 63 5 Third edition published in 2014 by Scion Publishing Ltd (978 1 907904 03 5) Second edition published in 2008 by Scion Publishing Ltd (978 1 904842 55 2) First edition published in 2003 by Martin Dunitz (1 85996 219 X) Scion Publishing Limited The Old Hayloft, Vantage Business Park, Bloxham Road, Banbury OX16 9UX, UK www.scionpublishing.com Important Note from the Publisher The information contained within this book was obtained by Scion Publishing Ltd from sources believed by us to be reliable. However, while every effort has been made to ensure its accuracy, no responsibility for loss or injury whatsoever occasioned to any person acting or refraining from action as a result of information contained herein can be accepted by the authors or publishers. Readers are reminded that medicine is a constantly evolving science and while the authors and publishers have ensured that all dosages, applications and practices are based on current indications, there may be specific practices which differ between communities.
    [Show full text]
  • History of Health Statistics
    certain gambling problems [e.g. Pacioli (1494), Car- Health Statistics, History dano (1539), and Forestani (1603)] which were first of solved definitively by Pierre de Fermat (1601–1665) and Blaise Pascal (1623–1662). These efforts gave rise to the mathematical basis of probability theory, The field of statistics in the twentieth century statistical distribution functions (see Sampling Dis- (see Statistics, Overview) encompasses four major tributions), and statistical inference. areas; (i) the theory of probability and mathematical The analysis of uncertainty and errors of mea- statistics; (ii) the analysis of uncertainty and errors surement had its foundations in the field of astron- of measurement (see Measurement Error in omy which, from antiquity until the eighteenth cen- Epidemiologic Studies); (iii) design of experiments tury, was the dominant area for use of numerical (see Experimental Design) and sample surveys; information based on the most precise measure- and (iv) the collection, summarization, display, ments that the technologies of the times permit- and interpretation of observational data (see ted. The fallibility of their observations was evident Observational Study). These four areas are clearly to early astronomers, who took the “best” obser- interrelated and have evolved interactively over the vation when several were taken, the “best” being centuries. The first two areas are well covered assessed by such criteria as the quality of obser- in many histories of mathematical statistics while vational conditions, the fame of the observer, etc. the third area, being essentially a twentieth- But, gradually an appreciation for averaging observa- century development, has not yet been adequately tions developed and various techniques for fitting the summarized.
    [Show full text]
  • Are Randomized Double-Blind Experiments Everything?
    Int. Statistical Inst.: Proc. 58th World Statistical Congress, 2011, Dublin (Session CPS056) p.5278 Are Randomized Double-blind Experiments Everything? Hampel, Frank Swiss Federal Institute of Technology (ETH), Dept. of Mathematics CH-8092 Zurich, Switzerland E-mail: [email protected] 1. Introduction and overview In medical statistics, randomized double-blind experiments are one of the most important tools. In order to test a new drug or treatment, it is applied to a randomly selected subgroup of patients, while the others obtain a comparison treatment or no treatment at all. Single blinding means that the patient does not know what he or she gets, and double blinding means that also the doctor who judges the effect does not know what has been applied. Obviously, this is to avoid any subjective biases, and it is necessary if the results are not clearcut. And the randomizing ensures that \in the long run" any significant differences are due to the treatment effects. Because of these nice properties, some medical statisticians strongly demand that all evidence should only come from such experiments, they consider it a panacea and seem to tend to ignore all other information. However, apart from this limited view, there are also some problems with this approach. One is obviously that the law of large numbers may not yet be applicable. To avoid this, bigger and bigger experiments are proposed, and/or many smaller experiments are combined in a meta-analysis. One danger is that the quality and homogeneity is much harder to ensure in big experiments, even more so in (tendentiously heterogeneous) parts of a meta-analysis.
    [Show full text]
  • Medical Statistics
    community project encouraging academics to share statistics support resources All stcp resources are released under a Creative Commons licence stcp-rothwell-types_of_trials The following resources are associated: Statistical Hypothesis testing, Medical Statistics Types of Trials There are a number of different ways that a hypothesis can be investigated and this sheet aims to provide an overview of the various trial types that can be conducted. The terms factor or hazard are used in this sheet and these are classed as exposures. For example, consider exposure to second-hand cigarette smoke, or intense sun exposure as a hazard or factor. They are something that could cause harm and are generally the factor which the researcher is interested in investigating. Randomised Controlled Trials Randomised controlled trials (RCTs) are the typical clinical trial or research study used to test a particular intervention (such as a drug or diet). Generally there is an experimental intervention of interest being tested against a standard intervention, often referred to as a control (such as current treatment or usual care), or a placebo (an intervention with no active properties). The format of these RCTs can vary, but there are two main types which are parallel group trials and cross over trials. Parallel Group Trials In a parallel group trial patients are randomly assigned to one of two treatment groups. The ideal scenario is that all other baseline characteristics of the patients are roughly similar in each group (i.e. equal number of males and females, location of hospital, patient ages, etc.). Randomisation of patients to treatment allocation is used to try to balance out the patient characteristics and this can be stratified by the characteristics that are deemed to be the most important or influential.
    [Show full text]
  • The Negative Aspects of Blinding in Trials
    BMJ Confidential: For Review Only Opening the blinds and shedding light on the risks and problems of blinding in clinical trials Journal: BMJ Manuscript ID BMJ-2019-050313 Article Type: Analysis BMJ Journal: BMJ Date Submitted by the 18-Apr-2019 Author: Complete List of Authors: Anand, Rohan; Queen's University Belfast, Wellcome-Wolfson Institute for Experimental Medicine Norrie, John; University of Edinburgh, Usher Institute of Population Health Sciences and Informatics Bradley, Judy; Queen's University Belfast, Wellcome-Wolfson Institute for Experimental Medicine McAuley, Daniel; Queen's University Belfast, Wellcome-Wolfson Institute for Experimental Medicine Clarke, Mike; Queen's University Belfast, Northern Ireland Methodology Hub blinding, placebos, clinical trials, pragmatic trials, clinical trial Keywords: methodology, RCT, PROBE, bias https://mc.manuscriptcentral.com/bmj Page 1 of 25 BMJ 1 2 3 1 Full Title: 4 5 6 7 2 Opening the blinds and shedding light on the risks and problems of blinding 8 9 3 10 in clinical trials 11 12 Confidential: For Review Only 13 4 Standfast: Blinding can have negative implications for a clinical trial. 14 15 16 5 Author Positions, Names and Emails: 17 18 19 6 Rohan Anand1, [email protected], (ORCiD: 0000-0002-1957-5336); 20 21 7 Professor John Norrie2, [email protected], 22 23 24 8 Professor Judy M Bradley3, [email protected], (ORCiD: 0000-0002-7423-135X) 25 26 9 Professor Danny F McAuley4, [email protected], (ORCiD: 0000-0002-3283-1947) 27 28 29 10 Professor Mike Clarke5, [email protected], (ORCiD: 0000-0002-2926-7257) 30 31 11 32 33 34 12 Author Affiliations and Addresses: 35 36 13 1 Doctoral Research Student in Clinical Trial Methodology; Wellcome-Wolfson Institute for 37 38 39 14 Experimental Medicine; School of Medicine, Dentistry and Biomedical Sciences; Queen's 40 41 15 University Belfast; Belfast; BT9 7BL; United Kingdom.
    [Show full text]
  • Review Article
    J Ayub Med Coll Abbottabad 2014;26(1) REVIEW ARTICLE STATISTICAL CONCEPTS IN BIOLOGY AND HEALTH SCIENCES Huma Zahir, Aisha Javaid*, Rehana Rehman*, Zahir Hussain** King Abdulaziz University (Formerly Department of Statistics, DHA College for Women, Karachi, Pakistan), * Department of Physiology, University of Karachi, Karachi, Pakistan, **Department of Physiology, Faculty of Medicine, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia In view of its applied aspects, Statistics serves as a separate mathematical science. In that respect, biostatistics is the application of statistical concepts and methods in biology, public health and medicine. One major task of medical biostatistics is to understand why a disease occurs in certain area and why that disease does not occur in other areas. In general, the advantages for properly applying statistics for a country are to keep the detailed information of people in a country. However, there must in mind be the other face of the task remembering not to adapt these surveys and limited data with entirety for quick applications that might be less advantageous. Some of the programs are much expensive and time consuming and people may feel not comfortable conveying their personal information just for the sake of applying a so called organized procedure. In such conditions, one must consider the moral values as well. Another quite unfortunate fact is that a statistical data can be misused for personal needs of a presenter. There must be ways to eradicate such customs at the governmental level. Basic and higher courses, certificate courses, diploma programs, degree programs, and other opportunities for students can be well organized and can be utilized in various employment areas in industry, government, life sciences, computer science, medicine, public health, education, teaching, research, and survey research.
    [Show full text]
  • Medical Statistics Made Easy
    MEDICAL STATISTICS MADE EASY STATISTICS MEDICAL Medical Statistics Made Easy 3rd edition continues to provide medical and healthcare students and professionals with the easiest possible explanations MEDICAL of the key statistical techniques used throughout the medical literature. Each statistical technique is graded for ease of use and frequency of appearance in the STATISTICS mainstream medical journals. Featuring a completely revised “Statistics at work” section, this new edition retains a consistent, concise and user-friendly format. MADE EASY Medical Statistics Made Easy 3rd edition is essential reading for anyone looking to understand concepts like: M. HARRIS and G. TAYLOR • confidence intervals and probability values • numbers needed to treat • t tests and other parametric tests • survival analysis 3rd EDITION If you need to understand the medical literature, then you need to read this book. Reviews of 2nd edition “Just about the only book on statistics that I’ve ever been able to understand. Not designed to teach you how to do statistics but how to tell what other people’s statistics actually mean. Contains really helpful explanations of the importance and meaning of most common (and many uncommon) statistical concepts that clinicians are likely to encounter in the medical literature.” 3 “I would recommend this book to be the first book to read if you want to HARRIS and TAYLOR understand medical statistics.” www.scionpublishing.com ISBN 978-1-907904-03-5 9 781907 904035 MEDICAL STATISTICS MADE EASY 3 Medical_Statistics_Made_Easy_3rd_edition_ccp.indd
    [Show full text]
  • Efficient Adaptive Designs for Clinical Trials of Interventions for COVID-19
    Efficient adaptive designs for clinical trials of interventions for COVID-19 Nigel Stallarda1, Lisa Hampsona*2, Norbert Benda3, Werner Brannath4, Tom Burnett5, Tim Friede6, Peter K. Kimani1, Franz Koenig7, Johannes Krisam8, Pavel Mozgunov5, Martin Posch7, James Wason9,10, Gernot Wassmer11, John Whitehead5, S. Faye Williamson5, Sarah Zohar12, Thomas Jakia5,10 1 Statistics and Epidemiology, Division of Health Sciences, Warwick Medical School, University of Warwick, UK. 2 Advanced Methodology and Data Science, Novartis Pharma AG, Basel, Switzerland 3 The Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany. 4 Institute for Statistics, University of Bremen, Bremen, Germany 5 Department of Mathematics and Statistics, Lancaster University, UK. 6 Department of Medical Statistics, University Medical Center Göttingen, Germany. 7 Section of Medical Statistics, CeMSIIS, Medical University of Vienna, Austria. 8 Institute of Medical Biometry and Informatics, University of Heidelberg, Germany. 9 Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK. 10 MRC Biostatistics Unit, University of Cambridge, Cambridge, UK. 11 RPACT GbR, Sereetz, Germany 12 INSERM, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, France * Corresponding author. [email protected] a These authors contributed equally Abstract The COVID-19 pandemic has led to an unprecedented response in terms of clinical research activity. An important part of this research has been focused on randomized controlled clinical trials to evaluate potential therapies for COVID-19. The results from this research need to be obtained as rapidly as possible. This presents a number of challenges associated with considerable uncertainty over the natural history of the disease and the number and characteristics of patients affected, and the emergence of new potential therapies.
    [Show full text]