Electronic Monitoring: Embedding digital accuracy into adherence measurement

If it is accepted that commonly used methods for measuring medication adherence can be flawed because trial patients are aware of monitoring taking place, then a crucial question arises: what would happen if an accurate measurement system could be employed that was entirely passive for patients?

The simple answer is that many of the fundamental problems associated with medication adherence in clinical trials would be removed. As a result, the value of the insights derived from the process would be enhanced.

With electronic monitoring, this theoretical situation is made real. Currently used in an estimated 2.7% of trials,[1] electronic monitoring is a concept first pioneered in the form of the MEMS? Cap. It has continued to evolve over decades of development and today describes a range of advanced, digitally based approaches to adherence measurement.

In typical applications, a microchip is integrated into drug packaging. This might be a pill bottle or blister pack, but it can also potentially be used with injectables, inhalers, cream tubes and containers for eye drops. When patients complete the action required to access or administer the medication from the packaging, a discreet timestamp is generated in real-time and transmitted by the chip, creating a digital log of dosing history.

Studies have shown that while these electronically recorded dosing histories might represent a measure of active dosing intent rather than direct evidence of ingestion, they do align with bioanalytical measures in 97% of cases. This demonstrates the ability of electronic monitoring to facilitate a data-rich continuous assessment of drug exposure between visits from trial coordinators.[2]

With a view to closing this ingestion-evidence gap entirely, electronic monitoring techniques have evolved further. An example is the ‘smart pill’, which is based on a patient-safe microcircuit being integrated within solid oral drug forms. The circuit is activated by gastric acid, triggering the generation of a weak radio signal that conveys information on the drug’s identity and the timing of ingestion. This signal is detected, amplified, and retransmitted to a more distant source via a signal-detection skin patch or necklace worn by the patient.

Smart pills are undoubtedly a highly effective means of proving ingestion, bringing significant value to focused settings such as Phase I studies. It is fair to say, however, that this particular method does face challenges when deployed at scale in terms of drug stability, patient intrusiveness and logistics.[3]

Sound preparation is critical to the successful implementation of electronic monitoring. This begins with selecting the appropriate device for data collection based on the requirements of the trial in question. Smart pill bottles or blisters have the capacity to generate substantial amounts of complex data related to medication adherence, and so it is important to consider how that data will be stored, managed and processed. Only then can stakeholders be assured that the resulting outputs will support the required analysis.

Where studies are correctly designed, electronically compiled adherence data achieves several key objectives:

For patients, the processed data delivers feedback on adherence behavior, fostering engagement and helping motivate them to participate fully in the study.

Investigators and study monitors can leverage the processed data to monitor patient adherence patterns, identify potential issues and make informed decisions regarding patient care.

Sponsors, who bear the responsibility for ensuring the success of the trial, can utilize the processed data to evaluate the impact of adherence on study outcomes and adjust strategies if needed.

These points show how the data-driven approach that underpins electronic monitoring has the potential to improve both the process of adherence measurement and the findings themselves. In doing so, it can elevate the success and integrity of drug trials – and all without adding burden to the patients who are taking part.

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[1] Mantila KM, Pasmooij AMG, Hallgreen CE, Mol PGM, van Boven JFM. Medication Adherence Measurement Methods in Registration Trials Supporting the Approval of New Medicines: A Cross-Sectional Analysis of Centralized Procedures in the European Union 2010-2020. Clin Pharmacol Ther. 2022 Nov;112(5):1051-1060. doi: 10.1002/cpt.2709. Epub 2022 Jul 30. PMID: 35816103; PMCID: PMC9795959.

[2] Vrijens B, Urquhart J. Methods for measuring, enhancing, and accounting for medication adherence in clinical trials. Clin Pharmacol Ther. 2014 Jun;95(6):617-26. doi: 10.1038/clpt.2014.59. Epub 2014 Mar 12. PMID: 24739446.

[3] Eisenberger U, Wüthrich RP, Bock A, Ambühl P, Steiger J, Intondi A, Kuranoff S, Maier T, Green D, DiCarlo L, Feutren G, De Geest S. Medication adherence assessment: high accuracy of the new Ingestible Sensor System in kidney transplants. Transplantation. 2013 Aug 15;96(3):245-50. Doi: 10.1097/TP.0b013e31829b7571. PMID: 23823651; PMCID: PMC3749815.