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=== Relationship with statistics ===
When the scientific method employs statistics as a key part of its arsenal, there are mathematical and practical issues that can have a deleterious effect on the reliability of the output of scientific methods. This is described in a popular 2005 scientific paper "Why Most Published Research Findings Are False" by [[John Ioannidis]], which is considered foundational to the field of [[metascience]].<ref>{{Cite journal|title = Why Most Published Research Findings Are False|journal = PLOS Medicine|date = 2005-08-01|issn = 1549-1277|pmc = 1182327|pmid = 16060722|volume = 2|issue = 8|pages = e124|doi = 10.1371/journal.pmed.0020124|first = John P.A.|last = Ioannidis | doi-access=free }}</ref> Much research in metascience seeks to identify poor use of statistics and improve its use.{{efn|name= misuseOfpValues|For example, see [[misuse of p-values]].}}{{efn|name= misuseTtests}} ''See [[Preregistration (science)#Rationale]]''
The particular points raised are statistical ("The smaller the studies conducted in a scientific field, the less likely the research findings are to be true" and "The greater the flexibility in designs, definitions, outcomes, and analytical modes in a scientific field, the less likely the research findings are to be true.") and economical ("The greater the financial and other interests and prejudices in a scientific field, the less likely the research findings are to be true" and "The hotter a scientific field (with more scientific teams involved), the less likely the research findings are to be true.") Hence: "Most research findings are false for most research designs and for most fields" and "As shown, the majority of modern biomedical research is operating in areas with very low pre- and poststudy probability for true findings." However: "Nevertheless, most new discoveries will continue to stem from hypothesis-generating research with low or very low pre-study odds," which means that *new* discoveries will come from research that, when that research started, had low or very low odds (a low or very low chance) of succeeding. Hence, if the scientific method is used to expand the frontiers of knowledge, research into areas that are outside the mainstream will yield the newest discoveries. ''See: [[Expected value of sample information]], [[False positives and false negatives]], [[Test statistic]], and [[Type I and type II errors]]''
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