References for the exposure metric guide

What the page cites, and what has actually been checked

The two sources cited by the Selecting an Exposure Metric page, with a status marker on each recording whether the page’s use of it has been verified against the source.

Neither source has been checked. Both citations came across from PK_Choosing_Metric_public.Rmd as links, and the page’s characterization of each is Andy’s from the source file rather than a reading done here. The bibliographic details below were fetched from Crossref and PubMed on 2026-09-02 and are correct; what is unverified is whether each paper says what the page uses it to say.

The page is Selecting an Exposure Metric, the working document is the specification, and the folder’s documents are on the project index.

Status markers

• ❌ Not checked. No claim on the page has been verified against this source.
• ⚠️ Transcribed, unverified. A number, table or figure on the page came from this source but has not been checked against it.
• ✅ Checked. The claim the page draws from it has been verified against the source.

Change a marker when the check is done, not when the paper is opened.

Reading queue

Two entries, in the order to read them.

1. ❌ Ruiz-Garcia et al., 2023. Read first. It is cited as the general companion to the whole page rather than for one claim, so reading it either confirms the page sits inside current practice or shows where it has drifted. Question to read against: does the review’s account of exposure metric selection in oncology agree with the four questions, and does it name a consideration the page omits?

2. ❌ Dumortier et al., 2015. Read second, and quickly. Only one claim depends on it and the claim is about a figure. Question to read against: does the paper show daily tacrolimus concentration with rejection events overlaid, and do most events fall below the median?

Sources

❌ Ruiz-Garcia A, Baverel P, Bottino D, Dolton M, Feng Y, González-García I, et al. A comprehensive regulatory and industry review of modeling and simulation practices in oncology clinical drug development. Journal of Pharmacokinetics and Pharmacodynamics 50:147–172, 2023. doi:10.1007/s10928-023-09850-2

Cited in the page’s opening as a useful companion. Nothing on the page depends on a specific number or figure from it, so the marker turns ✅ once the review has been read against the question in the queue above.

❌ Dumortier T, Looby M, Luttringer O, Heimann G, Klupp J, et al. Estimating the contribution of everolimus to immunosuppressive efficacy when combined with tacrolimus in liver transplantation: a model-based approach. Clinical Pharmacology and Therapeutics 97:411–418, 2015. PubMed 25669933

Cited in Section 3 as the pattern for a time-dependent exposure metric. The page describes a figure from it: daily tacrolimus concentration with organ rejection events drawn in black, most of them below the median. That description came across from the source R Markdown file and the figure itself was not in the upload, so it is unverified in both senses. See Section 4 of the specification.