BACKGROUND: Statistical hypothesis testing is much like gambling. If, with one statistical test, your chance of a significant result is 5%, then, after 20 tests, it will increase to 40%. This result is based on the play of chance. In current clinical trials, instead of a single efficacy-variable of one treatment, multiple efficacy-variables of more than one treatment are increasingly assessed. METHODS: The current paper reviews some methods for reducing the problem of falsely positive results due to multiple testing. RESULTS AND CONCLUSIONS: These methods include (1) the Bonferroni test, (2) the least significant difference (LSD) test, (3) other less conservative, more rarely used methods like Tukey's honestly significant difference (HSD) test, Dunnett's test, Student-Neuman-Keuls test, Hochberg's adjustment, and the Hotelling Q-square test. Alternative approaches to the problem of multiple testing include (4) the construct of composite endpoints, (5) no adjustment at all, but a more philosophical approach to the interpretation of the p-values, and (6) the replacement of the traditional 5% rejection level with a 1% rejection level or less. Evidence-based medicine is under pressure, because trials do not adequately apply to their target populations. As long as the effects of multiple testing are not routinely assessed in the analysis of clinical trials, it can not be excluded as one of the mechanisms responsible.
BACKGROUND: Statistical hypothesis testing is much like gambling. If, with one statistical test, your chance of a significant result is 5%, then, after 20 tests, it will increase to 40%. This result is based on the play of chance. In current clinical trials, instead of a single efficacy-variable of one treatment, multiple efficacy-variables of more than one treatment are increasingly assessed. METHODS: The current paper reviews some methods for reducing the problem of falsely positive results due to multiple testing. RESULTS AND CONCLUSIONS: These methods include (1) the Bonferroni test, (2) the least significant difference (LSD) test, (3) other less conservative, more rarely used methods like Tukey's honestly significant difference (HSD) test, Dunnett's test, Student-Neuman-Keuls test, Hochberg's adjustment, and the Hotelling Q-square test. Alternative approaches to the problem of multiple testing include (4) the construct of composite endpoints, (5) no adjustment at all, but a more philosophical approach to the interpretation of the p-values, and (6) the replacement of the traditional 5% rejection level with a 1% rejection level or less. Evidence-based medicine is under pressure, because trials do not adequately apply to their target populations. As long as the effects of multiple testing are not routinely assessed in the analysis of clinical trials, it can not be excluded as one of the mechanisms responsible.
Authors: Riad Salem; Robert J Lewandowski; Laura Kulik; Edward Wang; Ahsun Riaz; Robert K Ryu; Kent T Sato; Ramona Gupta; Paul Nikolaidis; Frank H Miller; Vahid Yaghmai; Saad M Ibrahim; Seanthan Senthilnathan; Talia Baker; Vanessa L Gates; Bassel Atassi; Steven Newman; Khairuddin Memon; Richard Chen; Robert L Vogelzang; Albert A Nemcek; Scott A Resnick; Howard B Chrisman; James Carr; Reed A Omary; Michael Abecassis; Al B Benson; Mary F Mulcahy Journal: Gastroenterology Date: 2010-10-30 Impact factor: 22.682
Authors: Khairuddin Memon; Laura Kulik; Robert J Lewandowski; Edward Wang; Robert K Ryu; Ahsun Riaz; Paul Nikolaidis; Frank H Miller; Vahid Yaghmai; Talia Baker; Michael Abecassis; Al B Benson; Mary F Mulcahy; Reed A Omary; Riad Salem Journal: J Hepatol Date: 2012-01-13 Impact factor: 25.083
Authors: Khairuddin Memon; Laura M Kulik; Robert J Lewandowski; Edward Wang; Jonathan Wang; Robert K Ryu; Ryan Hickey; Michael Vouche; Talia Baker; Daniel Ganger; Vanessa L Gates; Ali Habib; Mary F Mulcahy; Riad Salem Journal: J Vasc Interv Radiol Date: 2014-03-07 Impact factor: 3.464
Authors: Khairuddin Memon; Laura Kulik; Robert J Lewandowski; Edward Wang; Ahsun Riaz; Robert K Ryu; Kent T Sato; Karen Marshall; Ramona Gupta; Paul Nikolaidis; Frank H Miller; Vahid Yaghmai; Seanthan Senthilnathan; Talia Baker; Vanessa L Gates; Michael Abecassis; Al B Benson; Mary F Mulcahy; Reed A Omary; Riad Salem Journal: Gastroenterology Date: 2011-04-30 Impact factor: 22.682
Authors: Robert J Lewandowski; Khairuddin Memon; Mary F Mulcahy; Ryan Hickey; Karen Marshall; Melissa Williams; Krystina Salzig; Vanessa L Gates; Bassel Atassi; Michael Vouche; Rohi Atassi; Kush Desai; Elias Hohlastos; Kent Sato; Ali Habib; Sheetal Kircher; Steven B Newman; Halla Nimeiri; Al B Benson; Riad Salem Journal: Eur J Nucl Med Mol Imaging Date: 2014-06-07 Impact factor: 9.236
Authors: Alan Leviton; T Michael O'Shea; Francis J Bednarek; Elizabeth N Allred; Raina N Fichorova; Olaf Dammann Journal: Acta Paediatr Date: 2011-12-07 Impact factor: 2.299