Response to ‘What Kind of Controls to Use in CaseControl Studies of Malformed Infants: Recall BiasVersus “Teratogen Nonspecificity” Bias’

To the Editor:We read with interest the letter by Hook (’00) and

greatly appreciated his positive view of our work (Pri-eto and Martınez-Frias, ’99). Hook proposed the use ofboth healthy and malformed controls assuming thatthe true estimate of the relative risk is somewherebetween the values obtained from these two proce-dures. We fully agree with his suggestion, but wouldlike to add that an odds ratio (OR) with a magnitudeover the unity of using malformed infants as controls,could also result from the quotient of two protectiverelative risks. For this reason, the value obtained usingmalformed infants as controls when the factors beingstudied have a protective effect is not the lower limit ofthe true estimate of the relative risk. Thus, in studiesfor generating hypotheses for factors with unknowneffects, it is essential to use both healthy and mal-formed controls, not only as a way to control “recallbias” and “teratogen nonspecificity bias” as proposed byHook, but also to identify whether the factor is terato-genic or protective.

LUIS PRIETODepartamento de BioestadısticaFacultad de MedicinaUniversidad ComplutenseMadrid, Spain

MARIA LUISA MARTINEZ-FRIAS*Departamento de FarmacologıaFacultad de MedicinaUniversidad ComplutenseMadrid, Spain

LITERATURE CITED

Hook EB. 2000. What kind of controls to use in case control studies ofmalformed infants: recall bias versus “Teratogen nonspecificity”bias. Teratology 61:325–326.

Prieto L, Martınez-Frias ML. 1999. Case-control studies using onlymalformed infants: are we interpreting the results correctly? Tera-tology 60:1–2.

*Correspondence to: Marıa Luisa Martınez-Frias, ECEMC and De-partamento de Farmacologıa, Facultad de Medicina, UniversidadComplutense, Madrid 28040, Spain.E-mail: luisama@eucmos.sim.ucm.es

Received 1 July 2000; Accepted 9 July 2000

TERATOLOGY 62:372 (2000)

© 2000 WILEY-LISS, INC.