Interim analyses of data as they accumulate in laboratory experimentation. 2003

John Ludbrook
Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia. ludbrook@bigpond.net.au

BACKGROUND Techniques for interim analysis, the statistical analysis of results while they are still accumulating, are highly-developed in the setting of clinical trials. But in the setting of laboratory experiments such analyses are usually conducted secretly and with no provisions for the necessary adjustments of the Type I error-rate. CONCLUSIONS Laboratory researchers, from ignorance or by design, often analyse their results before the final number of experimental units (humans, animals, tissues or cells) has been reached. If this is done in an uncontrolled fashion, the pejorative term 'peeking' has been applied. A statistical penalty must be exacted. This is because if enough interim analyses are conducted, and if the outcome of the trial is on the borderline between 'significant' and 'not significant', ultimately one of the analyses will result in the magical P = 0.05. I suggest that Armitage's technique of matched-pairs sequential analysis should be considered. The conditions for using this technique are ideal: almost unlimited opportunity for matched pairing, and a short time between commencement of a study and its completion. Both the Type I and Type II error-rates are controlled. And the maximum number of pairs necessary to achieve an outcome, whether P = 0.05 or P > 0.05, can be estimated in advance. CONCLUSIONS Laboratory investigators, if they are to be honest, must adjust the critical value of P if they analyse their data repeatedly. I suggest they should consider employing matched-pairs sequential analysis in designing their experiments.

UI MeSH Term Description Entries
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D012107 Research Design A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. Experimental Design,Data Adjustment,Data Reporting,Design, Experimental,Designs, Experimental,Error Sources,Experimental Designs,Matched Groups,Methodology, Research,Problem Formulation,Research Methodology,Research Proposal,Research Strategy,Research Technics,Research Techniques,Scoring Methods,Adjustment, Data,Adjustments, Data,Data Adjustments,Design, Research,Designs, Research,Error Source,Formulation, Problem,Formulations, Problem,Group, Matched,Groups, Matched,Matched Group,Method, Scoring,Methods, Scoring,Problem Formulations,Proposal, Research,Proposals, Research,Reporting, Data,Research Designs,Research Proposals,Research Strategies,Research Technic,Research Technique,Scoring Method,Source, Error,Sources, Error,Strategies, Research,Strategy, Research,Technic, Research,Technics, Research,Technique, Research,Techniques, Research
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D003627 Data Interpretation, Statistical Application of statistical procedures to analyze specific observed or assumed facts from a particular study. Data Analysis, Statistical,Data Interpretations, Statistical,Interpretation, Statistical Data,Statistical Data Analysis,Statistical Data Interpretation,Analyses, Statistical Data,Analysis, Statistical Data,Data Analyses, Statistical,Interpretations, Statistical Data,Statistical Data Analyses,Statistical Data Interpretations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006805 Human Experimentation The use of humans as investigational subjects. Human Research Subject Protection,Experimentation, Human
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016001 Confidence Intervals A range of values for a variable of interest, e.g., a rate, constructed so that this range has a specified probability of including the true value of the variable. Confidence Interval,Interval, Confidence,Intervals, Confidence
D032761 Animal Experimentation The use of animals as investigational subjects. Animal Experimental Use,Animal Experiments,Animal Research,Animal Experiment,Animal Experimental Uses,Experiment, Animal,Experimental Use, Animal,Experimental Uses, Animal,Experimentation, Animal,Experiments, Animal,Research, Animal

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