How many NMLE articles are published in higher Impact Factor clinical journals?

Background: Pharmacometrics aims to understand the drug-patient interaction, connects various fields such as physiology, pharmacology, pharmacotherapy, clinical pharmacy, mathematical modelling, statistics, systems biology, pharmacokinetics/-dynamics in a coherent framework to improve drug development and patient therapy outcomes. The aim of this review was to identify publications that have applied the nonlinear mixed effects (NLME) modelling approach since its first appearance in 1980, and have been published in high impact clinical journals.

Methods: The search terms “nonlinear mixed effect modeling” OR “nonlinear mixed effect modelling” OR nonmem OR monolix OR pharmacometric* were used to search three databases (Pubmed, Web of Science and Embase)  for articles published in English between 1980  and August 2018 (time of the search). Journal impact factor were identified via Web of Science or the journal’s webpage and recorded as per October 2018.

Results: 10,893 articles were identified; after duplication were removed and titles and abstracts were scanned 4,387 articles remained. A continuously increasing number of articles were published in 578 unique journals with 51% of articles published in 11 journals. Articles identified were published in journals with impact factors ranging from 0.1 to 26.3 (Journal of Clinical Oncology). The median impact factor was 3.08. 10.6% articles are published in journals with no impact factor. 2.2% of articles applying or developing methods in the field of NLME are published in Journals with IF> 6. Over 64.9% of articles had a first/corresponding author from academia, 27.7% from a hospital and 7.4% from industry. The most common author teams were academics and clinicians (38.1%) followed by academics and authors from industry (14.9%). When published, presentation of the methods used and the description of the results was seldom according to standards. [1, 2]

Conclusions: Communication of the impact of the results arising from NLME studies needs to improve, peer-review within the area need to increase outside the academic setting and engagement with statistician and clinicians need to improve.


  1. Jamsen KM, McLeay SC, Barras MA, Green B. Reporting a population pharmacokinetic-pharmacodynamic study: a journal’s perspective. Clinical pharmacokinetics. 2014;53(2):111-22.
  2. European Medicines Agency, Committee for medicinal products for human use. Guidline on reporting the results of  population pharmacokinetic analyses. CHMP/EWP/185990/06. London 2007.


Stefanie Hennig