If side effects from a prescribed medication could affect the safety of a donor's work, the Medical Review Officer (MRO) must determine the appropriate course of action regarding this information. While the Mandatory Guidelines specify that an MRO should confirm a drug test as negative if the donor has a valid prescription, it is advisable for the MRO to communicate with the prescribing physician. This dialogue can help assess how the medication might influence the safety of the donor's work duties.

Additionally, either the donor or the Federal agency may occasionally ask the laboratory for an inclusive set of analytical data, chain of custody records, and other administrative documents linked to the testing of a specific specimen. This compilation of documents is sometimes referred to as a "documentation package," "data package," or "litigation package," and all requests for such information must be channeled through the MRO to the testing facility.

A positive will be rendered with the specimen’s immunoassay result was at or above the initial test cutoff for the drug class and the specimen’s confirmatory drug test result (i.e., on a separate [fractional part of a specimen used for testing, representing the whole specimen]) was at or above the confirmatory test cutoff for the specific drug/drug metabolite.