The article titled “Individual deviations of human chorionic gonadotropin concentrations during pregnancy” was published in March 2011 (Am J Obstet Gynecol 2011;204:349.e1-7). The Journal received an allegation that the author failed to declare conflict of interest and that the assays that were used for determinations of human chorionic gonadotropin (hCG) and luteinizing hormone (LH) were flawed. In accordance with the published guidelines of the Journal, the initial inquiry process was conducted to investigate the allegation.
The inquiry committee of 3 independent experts in the field reviewed all related documents and the author’s response to questions that had been raised and concluded that the author violated the guidelines of the Journal’s specific inappropriate acts in the publication process.
Issue on Conflict of Interest
The panel concluded that an undisclosed conflict of interest existed. Charles & Dwight Co (C&D) is the manufacturer of First Response home pregnancy and home ovulation tests, and the study findings might have influence on these products and other similar products. The author acknowledged that he had contract research with funding for C&D from 2004-2008. The urine samples that were used for the study that was reported in the article came from his previous studies, which had been funded by C&D under the contract; the study period was July-December 2009. The panel concluded that that fact clearly constitutes a conflict of interest that should have been disclosed. Failure to disclose conflicts of interest is a serious violation of publication principle/guidelines.
Scientific Issues
Rationale of the study
The author states “It is well-known that total human chorionic gonadotropin (hCG) levels in serum and urine samples vary tremendously between individuals. In fact pregnancy hCG concentrations vary among individuals so greatly that hCG measurements are of little use in dating a pregnancy.” Other investigators have shown repeatedly that hCG measurements are highly variable. There is no credible scientific reason given for conducting the study.
Methodologic flaws
Author responsibility
The author used Siemens Immulite 1000 for both hCG and LH measurements in urine. The validation information shown is for hCG assay and should have included LH, especially when the urine sample might not be a suitable matrix for Siemens Immulite LH assay. One major point of the study was linking hCG levels to the LH surge. The product information clearly states that the Immulite Analyzers are for the qualitative measurement of hCG in serum and for strictly qualitative determinations in urine. The procedure for urine samples is designed solely as a screen for pregnancy, with the use of a 30-mIU/mL cutoff.
Assay sensitivity
The limit of sensitivity was not identified in a typical manner. When asked to respond to this issue the author responded that no official sensitivity was set and that “no patient samples were detected for clinical purposes, just research patient samples.” The panel concluded that the sensitivity should have been set for the study, that the linearity should be over the range of the tested samples and/or dilutional standards, and that the impact of dilution should have been included.
Creatinine concentrations
There is a discussion regarding the significant variation in creatinine concentrations, yet no correction was exercised for the impact of urinary concentration. This might be the source of the variation of the rise within a single individual pregnancy and not an intrinsic variability as proposed.
Implantation range
Assessment of the implantation date from ovulation is questionable because it would be biologically impossible for implantation to occur as early as 3 days after the LH surge or 2 days after ovulation. The calculation likely was compromised by the lack of sensitivity at the lower end of the assay for LH and by the fact that the Immulite is not suitable for LH determination in urine. The article indicates that the author validated the Immulite for quantification of hCG in urine, but not of LH in urine.
Based on the inquiry report and recommendations, the Editorial Board concluded that the author committed specific inappropriate acts in publication: (1) failure to disclose the conflict of interest and (2) methodologic flaws and obfuscation.
Transparency in scientific publication is demanded by the readers, the scientific community, and the public. Failure to disclose conflicts of interest, even if inadvertently, causes public distrust. Also, it is the responsibility of authors to identify and validate methods that are used in a study and to report with clarity so as not to cause any confusion for readers. The Editorial Board decided to retract the article and to sanction the author appropriately. Although we regret that the article was published before we learned about and investigated the inappropriate acts, the editors and publishers hope that the readers will appreciate that the decision to retract the article reflects the commitment of the Journal to scientific integrity.
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