OBJECTIVE: Pharmacogenetics promises to individualize therapeutics. Concerns, however, exist about the lack of replication of discoveries. Selective use of different endpoints, times of assessment, types of interventions and genetic groups across studies may lead to spurious results. Here, we examined the variability of definitions of endpoints and analyses reported across studies addressing the association of the Arg16Gly and/or Gln27Glu polymorphisms of the beta2-adrenergic receptor gene with clinical response to beta2-agonist therapy in asthma. METHODS: We systematically calculated the number and type of endpoints and analyses reported across studies and recorded the appraisal of their statistical significance. RESULTS: Across 21 studies, the total number of probed and reported associations was 487 when the multiple endpoints and types of comparisons presented by multiple comparisons were considered (337 for Arg16Gly, 98 for Gln27Glu and 52 for their haplotypes): 465 (95%) were probed only once; only six associations were probed twice and two associations were probed five times, for the same endpoint, time of assessment, type of interventions and genetic group. Most studies (17/21) claimed at least one significant association. Overall, however, 243/487 (49.9%) probed and reported associations were not statistically significant, 120 (24.6%) were of unspecified statistical significance, 86 (17.7%) were statistically significant only for specific selected genetic contrasts and only 38 (7.8%) were genuinely statistically significant for the comparison between all available genetic groups. CONCLUSIONS: The multifarious outcomes in this literature are inconsistent across studies and susceptible to selective reporting. The lack of standardization hinders the evaluation of replication validity for reported discoveries.
OBJECTIVE: Pharmacogenetics promises to individualize therapeutics. Concerns, however, exist about the lack of replication of discoveries. Selective use of different endpoints, times of assessment, types of interventions and genetic groups across studies may lead to spurious results. Here, we examined the variability of definitions of endpoints and analyses reported across studies addressing the association of the Arg16Gly and/or Gln27Glu polymorphisms of the beta2-adrenergic receptor gene with clinical response to beta2-agonist therapy in asthma. METHODS: We systematically calculated the number and type of endpoints and analyses reported across studies and recorded the appraisal of their statistical significance. RESULTS: Across 21 studies, the total number of probed and reported associations was 487 when the multiple endpoints and types of comparisons presented by multiple comparisons were considered (337 for Arg16Gly, 98 for Gln27Glu and 52 for their haplotypes): 465 (95%) were probed only once; only six associations were probed twice and two associations were probed five times, for the same endpoint, time of assessment, type of interventions and genetic group. Most studies (17/21) claimed at least one significant association. Overall, however, 243/487 (49.9%) probed and reported associations were not statistically significant, 120 (24.6%) were of unspecified statistical significance, 86 (17.7%) were statistically significant only for specific selected genetic contrasts and only 38 (7.8%) were genuinely statistically significant for the comparison between all available genetic groups. CONCLUSIONS: The multifarious outcomes in this literature are inconsistent across studies and susceptible to selective reporting. The lack of standardization hinders the evaluation of replication validity for reported discoveries.
Authors: Katherine A Drake; Dara G Torgerson; Christopher R Gignoux; Joshua M Galanter; Lindsey A Roth; Scott Huntsman; Celeste Eng; Sam S Oh; Sook Wah Yee; Lawrence Lin; Carlos D Bustamante; Andrés Moreno-Estrada; Karla Sandoval; Adam Davis; Luisa N Borrell; Harold J Farber; Rajesh Kumar; Pedro C Avila; Emerita Brigino-Buenaventura; Rocio Chapela; Jean G Ford; Michael A Lenoir; Fred Lurmann; Kelley Meade; Denise Serebrisky; Shannon Thyne; William Rodríguez-Cintrón; Saunak Sen; José R Rodríguez-Santana; Ryan D Hernandez; Kathleen M Giacomini; Esteban G Burchard Journal: J Allergy Clin Immunol Date: 2013-08-29 Impact factor: 10.793
Authors: Alfredo Panebra; Mary Rose Schwarb; Clare B Glinka; Stephen B Liggett Journal: Am J Respir Cell Mol Biol Date: 2007-01-25 Impact factor: 6.914
Authors: Julian Little; Julian P T Higgins; John P A Ioannidis; David Moher; France Gagnon; Erik von Elm; Muin J Khoury; Barbara Cohen; George Davey-Smith; Jeremy Grimshaw; Paul Scheet; Marta Gwinn; Robin E Williamson; Guang Yong Zou; Kim Hutchings; Candice Y Johnson; Valerie Tait; Miriam Wiens; Jean Golding; Cornelia van Duijn; John McLaughlin; Andrew Paterson; George Wells; Isabel Fortier; Matthew Freedman; Maja Zecevic; Richard King; Claire Infante-Rivard; Alex Stewart; Nick Birkett Journal: Hum Genet Date: 2009-02-01 Impact factor: 4.132
Authors: Blanca E Himes; Ann Chen Wu; Qing Ling Duan; Barbara Klanderman; Augusto A Litonjua; Kelan Tantisira; Marco F Ramoni; Scott T Weiss Journal: Pharmacogenomics Date: 2009-09 Impact factor: 2.533
Authors: Julian Little; Julian P T Higgins; John P A Ioannidis; David Moher; France Gagnon; Erik von Elm; Muin J Khoury; Barbara Cohen; George Davey-Smith; Jeremy Grimshaw; Paul Scheet; Marta Gwinn; Robin E Williamson; Guang Yong Zou; Kim Hutchings; Candice Y Johnson; Valerie Tait; Miriam Wiens; Jean Golding; Cornelia van Duijn; John McLaughlin; Andrew Paterson; George Wells; Isabel Fortier; Matthew Freedman; Maja Zecevic; Richard King; Claire Infante-Rivard; Alex Stewart; Nick Birkett Journal: PLoS Med Date: 2009-02-03 Impact factor: 11.069
Authors: Julian Little; Julian P T Higgins; John P A Ioannidis; David Moher; France Gagnon; Erik von Elm; Muin J Khoury; Barbara Cohen; George Davey-Smith; Jeremy Grimshaw; Paul Scheet; Marta Gwinn; Robin E Williamson; Guang Yong Zou; Kim Hutchings; Candice Y Johnson; Valerie Tait; Miriam Wiens; Jean Golding; Cornelia van Duijn; John McLaughlin; Andrew Paterson; George Wells; Isabel Fortier; Matthew Freedman; Maja Zecevic; Richard King; Claire Infante-Rivard; Alex Stewart; Nick Birkett Journal: Eur J Clin Invest Date: 2009-04 Impact factor: 4.686
Authors: Julian Little; Julian P T Higgins; John P A Ioannidis; David Moher; France Gagnon; Erik von Elm; Muin J Khoury; Barbara Cohen; George Davey-Smith; Jeremy Grimshaw; Paul Scheet; Marta Gwinn; Robin E Williamson; Guang Yong Zou; Kim Hutchings; Candice Y Johnson; Valerie Tait; Miriam Wiens; Jean Golding; Cornelia van Duijn; John McLaughlin; Andrew Paterson; George Wells; Isabel Fortier; Matthew Freedman; Maja Zecevic; Richard King; Claire Infante-Rivard; Alex Stewart; Nick Birkett Journal: Eur J Epidemiol Date: 2009-02-03 Impact factor: 8.082