RESPONSE TO DR. FINUCANE

Abstract

To the Editor: We previously addressed Dr. Finucane's critique of our article.1, 2 We will therefore focus on his comparisons of our article to the work of Dr. Lopez et al.3 and the AD 2000 trial.4 Our study and the Lopez et al. study both support a role for cholinesterase inhibitors in the treatment of Alzheimer's disease (AD), specifically as they pertain to delayed nursing home placement. Otherwise, even a cursory review reveals considerable differences in the research paradigm, funding agency, subject ascertainment, and analytical methods between studies. Dr. Finucane repeats the incorrect assertion that we omitted differences in caregiver characteristics from our report. We explicitly state on p. 940 that caregiver type (spouse vs nonspouse) was included as a covariate in our analysis and that there were no statistically significant differences in the proportion of spousal caregivers across our exposure groups.2 We concur with Dr. Finucane that our study and the report by Dr. Lopez et al. are both easily distinguished from the AD 2000 trial, but Dr. Finucane fails to acknowledge major methodological shortcomings of the AD 2000 trial, including the facts that systematic diagnosis of AD was not required for entry into that study, investigators were instructed to enroll only subjects in whom treatment response could not be predicted (excluding those patients who were likely to show a treatment response), and marked underenrollment and excessive attrition rates were likely to have exerted significant biases on the interpretation of the data. Dr. Finucane's uncritical endorsement of the AD 2000 conclusions also does not acknowledge the approximately 70% likelihood of a Type II statistical error in the published interpretation, by which an actual effect would be undetected by the analysis as conducted.5 Although openly critical of studies associated with the pharmaceutical industry, Dr. Finucane fails to note the substantial risk for sponsor bias in AD 2000, which the principal payor for medications in the United Kingdom funded. Dr. Finucane also omits mention of the incomplete status of the proposed revision from the recently renamed National Institute for Health and Clinical Excellence regarding medications for Alzheimer's disease. The text accompanying the revision explicitly states: “Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation.”6 Dr. Finucane's assertion of a data/rhetoric mismatch therefore appears to apply quite well to his own criticism of treatments for Alzheimer's disease. Financial Disclosure: David S. Geldmacher receives research support from Eisai, Inc., Takeda Pharmaceuticals North America, and Myriad Pharmaceuticals; is a consultant for Eisai, Inc., Forest Laboratories, Glaxo-Smith-Kline, Myriad, and Pfizer, Inc.; and serves as a speaker for Eisai, Forest Laboratories, Johnson & Johnson, and Pfizer. George Provenzano is an employee of Battelle, which conducted statistical analyses under direction of and with funding from Eisai, Inc. and Pfizer, Inc. Thomas McRae is an employee of Pfizer, Inc. John R. Ieni is an employee of Eisai, Inc. Author Contributions: David S. Geldmacher, George Provenzano, Thomas McRae, and John R. Ieni all contributed equally in preparing this response. Sponsor's Role: Eisai, Inc. and Pfizer, Inc. sponsored the study that Dr. Finucane cites,2 but there was no sponsorship associated with the preparation of this response.