Research misconduct and the INTERGROWTH-21st study
Authors: Richard Horton, Sabine Kleinert, Sarah Linklater, Zoë Mullan
Journal: The Lancet Global Health (2017)

On Oct 20, 2016, a statement appeared on the WHO website, announcing that “An independent review commissioned by WHO has found that research ethics misconduct occurred in a study on foetal growth standards.”1WHOResearch dispute on fetal growth standard studies referred to the UK General Medical Council.http://www.who.int/reproductivehealth/topics/maternal_perinatal/research-dispute/en/Date: Oct 20, 2016Google Scholar The study in question was the INTERGROWTH-21st study, led by researchers at the University of Oxford, UK, funded by the Bill & Melinda Gates Foundation (BMGF), and reported in several journals, including our own.2Villar J Ismail LC Victora CG et al.International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project.Lancet. 2014; 384: 857-868Summary Full Text Full Text PDF PubMed Google Scholar, 3Papageorghiou AT Ohuma EO Altman DG et al.International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.Lancet. 2014; 384: 869-879Summary Full Text Full Text PDF PubMed Scopus (525) Google Scholar, 4Villar J Papageorghiou AT Pang R et al.The likeness of fetal growth and newborn size across non-isolated populations in the INTERGROWTH-21st Project: the Fetal Growth Longitudinal Study and Newborn Cross-Sectional Study.Lancet Diabet Endocrinol. 2014; 2: 781-792Summary Full Text Full Text PDF PubMed Scopus (189) Google Scholar, 5Villar J Giuliani F Bhutta ZA et al.Postnatal growth standards for preterm infants: the Preterm Postnatal Follow-up Study of the INTERGROWTH-21st Project.Lancet Glob Health. 2015; 3: e681-e691Summary Full Text Full Text PDF PubMed Scopus (194) Google Scholar Such a judgment by the world's foremost global health agency was serious, casting damaging light on a study of international importance. On Nov 16, 2016, we wrote to Ian Smith, Executive Director of the Office of the WHO Director-General, to request a copy of the review report, but were told that it was confidential and had been supplied only to the University of Oxford, BMGF, and the UK General Medical Council, which was considering whether to open an investigation of its own. We then wrote, on Nov 23, 2016, to the researchers, Stephen Kennedy and José Villar at the University of Oxford, to request their response to the review's findings. We subsequently received a letter from the University's Registrar, Ewan McKendrick, reiterating the history of the dispute, which (as we were aware) dates back to 2008 and has been the subject of previous investigations by the University of Oxford, the Committee on Publication Ethics (COPE), and other journals. In brief, the dispute surrounds allegations of plagiarism and disputes over intellectual ownership concerning two research protocols with joint origins: those of the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) and the WHO Multicentre Study for the Development of Growth Standards from Fetal Life to Childhood. Both protocols were drawn up in response to a 1995 WHO Expert Committee report6WHOPhysical status: the use and interpretation of anthropometry. World Health Organization, Geneva1995http://apps.who.int/iris/bitstream/10665/37003/1/WHO_TRS_854.pdfGoogle Scholar that recommended, among other things, “Assessment and development of fetal growth reference data suitable for international applications”. Both protocols also built on the methods of the WHO Multicentre Growth Reference Study,7De Onis M Garza C Victora CG et al.The WHO Multicentre Growth Reference Study: planning, study design, and methodology.Food Nutr Bull. 2004; 25: S15-S26Crossref PubMed Google Scholar which produced growth curves for children from birth to 5 years. Much of the bases of the protocols are therefore in the public domain. Kennedy and Villar are accused of having plagiarised the WHO Multicentre Study protocol in developing the INTERGROWTH-21st protocol and of obtaining rival funding while still involved with the WHO work. McKendrick's responses to us, on Nov 29, 2016, and Dec 13, 2016, were robust. It is clear from this response that the University of Oxford looked into these serious allegations at a high level, methodically dissected the claims, closely examined four pairs of protocols at different stages of development, engaged with the WHO Director-General, and retrieved supporting documentation before concluding that the allegations were unfounded. The Oxford researchers clearly stated the methodological foundations of INTERGROWTH-21st in their reports. We were aware, however, that we had only heard the University's version of events, and again pressed WHO for their inquiry report. This document was eventually shared with us in confidence on Jan 16, 2017, but we found it disappointingly insubstantial. We have therefore concluded that its far-reaching judgment of research misconduct is unproven, and gives no cause for concern regarding the reliability of the published data. Plagiarism of words and ideas is a serious academic offence. However, on the basis of the evidence we have seen, we cannot agree that an idea (namely the construction of growth curves for fetuses) has been plagiarised from WHO: an international group of experts (including Villar) posed the question in 1995.6WHOPhysical status: the use and interpretation of anthropometry. World Health Organization, Geneva1995http://apps.who.int/iris/bitstream/10665/37003/1/WHO_TRS_854.pdfGoogle Scholar Furthermore, building on work that has gone before is what drives advances in knowledge. As for the overlap between the protocols, we have not repeated the direct comparisons of the University of Oxford and the WHO independent expert review panel, the former having produced percentage overlap data and critical content analysis. However, recent publication of the headline growth curves from the WHO Multicentre Study8Kiserud T Piaggio G Carroli G et al.The World Health Organization Fetal Growth Charts: a multinational longitudinal study of ultrasound biometric measurements and estimated fetal weight.PLoS Med. 2017; 14: e1002220Crossref PubMed Scopus (358) Google Scholar indicates that the key aims were somewhat different: while INTERGROWTH-21st only reports ultrasound measures of head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length, the WHO Multicentre Study additionally shows estimated fetal weight. The episode seems to us a sad example of academic rivalry and miscommunication, one that has been repeatedly investigated and previously put to rest. As far as we can ascertain, the recent inquiry by the WHO independent expert review panel has shed no new light on the matter and does not give us any reason at this stage to question the veracity of the papers we have published. ZM is a Trustee and Council Member of COPE. The other authors declare no competing interests. Research misconduct and the INTERGROWTH-21st studyWe respectfully take issue with the Comment published in February, 2017, by members of The Lancet's editorial staff stating that WHO's judgment of misconduct regarding the Oxford INTERGROWTH-21st study was unproven.1–3 We are saddened by the fact that they base their conclusion on limited and biased material and simply dismiss the case as rivalry. As members of the WHO Fetal Growth research group and a former WHO external expert not associated with that trial but with evidence that WHO initially refused to hear, we wish to note the following. Full-Text PDF Open Access