Leverage clinical trial results through drug adherence



Sponsors and regulators have long known that poor drug adherence is a threat to the success of clinical trials. How to fix the problem, however, has not been so clear. Until now.

In recent years, digital adherence monitoring, with its ability to track doses, trace drug-taking behavior, and inform individualized interventions, has become an evidence-based way to leverage trial results. clinics.

In this article, we will discuss the problem of adhesion and how it can negatively affect research, before demonstrating how modern surveillance systems have the advantage over traditional methods.

Admission and failure of the trial
The reasons for the study failure are as varied and complex as the trials themselves, but a common thread runs through many: poor drug adherence, which affects about 50% of all clinical trial participants.1

According to a 2018 review of data from the previous 30 years, the main source of trial failure is the inability to demonstrate efficacy.2 A study, by Hwang et al, of 640 phase III trials of new therapies, found that 54% of them had failed in clinical development. Of these, 57% were attributed to insufficient efficacy.3

But that doesn’t necessarily mean the drug didn’t work. The result could, for example, be the result of an incorrect dosage or a low power study,2 both are common consequences of poor treatment adherence.

Safety is another common cause of study collapse, with Hwang et al finding that this was the root cause of failure in 17% of the phase III trials analyzed.3

However, unmanaged drug adherence often results in distorted risks / benefits, and safety concerns can result from selecting an unfortunate regimen or a higher total dose than necessary for adherent patients.4

It takes 10 to 12 years and over £ 550million4 in developing a new drug, poor adherence to the test protocol is then a costly problem.

The problem with traditional methods
Sponsors and CROs have grappled with the financial and logistical challenges of poor drug adherence for decades.

To date, they have been forced to rely on the only methods available – tablet counting, blood sampling and HCP or self-report. However, these traditional approaches are not sensitive enough to provide real added value.

The count of returned tablets is easily censored by participants. In addition, it only provides a summary of compliance between site visits, rather than an overall understanding of treatment initiation and dosing schedules.

Self-reporting, in which participants record their doses in a diary, for example, is vulnerable to inaccuracies, bias, and places an additional burden on the study participant. The same is true with different methods of journals, including print and digital applications, although they feature recalls and other advanced technologies that record evidence of ingestion. Resulting in poor data quality and increased fraud due to inconvenience to patients.5

Likewise, monitoring the drug or its metabolites in blood, urine, or hair provides only insight into adherence. So-called “white coat adhesion”, which means that people only take the investigational product the day before their on-site visit, is a concern. It is invasive, heavy, and its use is largely limited to the active arms of a trial.

The smart way to monitor membership
Digital monitoring using smart packages is frictionless for patients, therefore objective and accurate, and provides a holistic view of drug-taking behavior.

The solution combines smart drug packaging, such as connected inhalers, blisters and container caps, with powerful data analysis.

The microcircuits contained in the packaging automatically record the administration of the doses and transmit the information to the software of the study team. For example, connected pre-filled syringes collect and send essential information, including whether the injection was completed, as well as the time and date of administration.

A cloud-based platform then uses sophisticated algorithms to analyze drug-taking behavior and uses data visualizations to report any erratic dosing pattern.

By identifying participants who may be at risk for poor adherence, study teams can adapt to that person’s personal non-adherence factors.

This advanced approach is achievable, reliable and easy to implement. It is continuous, which means that it provides a holistic and non-invasive picture, placing no additional burden on staff or participants.

Basically it is evidence based. Studies have shown that smart packaging monitoring is 97% accurate, compared to 60% for pill counting, 50% for healthcare professional assessment and only 27% for self-report.6

Smart digital adhesion packaging solutions therefore provide sponsors and CROs with the tools they need to improve drug-taking behaviors, mitigating the risk of study failure and increasing their return on investment. .

1. Eliasson, L., Clifford, S., et al. How the EMERGE guideline on therapeutic adherence can improve the quality of clinical trials. (2020). https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bcp.14240
2. Fogel, D. Factors associated with failed clinical trials and opportunities for improving the odds of success: a review. (2018). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092479/
3. Hwang, T., Carpenter., D. et al. Failure of investigational drugs in late clinical development and publication of trial results. (2016) https://pubmed.ncbi.nlm.nih.gov/27723879/
4. Breckenridge, A., Aronson, J., et al. Poor drug adherence in clinical trials: consequences and solutions. (2017). https://www.nature.com/articles/nrd.2017.1?WT.ec_id=NRD-201703&spMailingID=53536275&spUserID=ODkwMTM2NjI2OQS2&spJobID=1120295377&spReportId=MTEyMDI5NTM3NwS2
5. Larson., K, Areberg J., et al. Clinical Trials1–6. DOI: 10.1177 / 17407745211012683 journals.sagepub.com/home/ctj
6. Greener, M. Drug development: from the bench to the bedside. (2013) https://www.magonlinelibrary.com/doi/abs/10.12968/npre.2010.8.2.46589 accessed May 19, 2021.

Dr. Vrijens holds a PhD from the Department of Applied Mathematics and Computer Science at the University of Ghent, Belgium. He is currently leading a research program studying (a) the most common dosing errors using a simple but robust taxonomy, (b) the particular dosing errors that can compromise the efficacy of a drug, and (c) the optimal measurement-driven drug management program. that can improve medication adherence and maintain long-term persistence. Dr Vrijens is also co-author of seven book chapters, over 100 peer-reviewed scientific papers and named inventor of 6 patents. He is a founding member of the International Society for Medication Adherence (ESPACOMP) and an active member of several EU and US funded collaborative projects on the topic of medication adherence.



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