Adherence and Accuracy: Smart packaging advances the quality imperative in clinical trials

Clinical trials are only as good as the quality of data they generate, and the quality of data they generate depends on the reliability of the information that is collected from trial participants regarding adherence to dosing instructions. Researchers need reliable and precise data to ensure that any observed effects or outcomes in the trial can be attributed to the drug itself, rather than inconsistencies in dosing intake.

Increasingly, drugs being developed today have a much narrower window between safety and efficacy, which means that these drugs are less forgiving of missed doses, and missed doses may have a significant impact on patients reaching a healthy outcome. In addition, new therapies entering clinical trials often have more complex dosing requirements and may require longer duration studies. These and other factors that can challenge a patient’s ability to adhere to dosing protocols.  Smart packaging and other adherence measurement solution address these challenges head on, by transforming medication management in clinical trials. Smart packages are available for most drug delivery formats (bottles, blisters, injectables, etc.), and the common feature and benefit they all share is they can passively measure the date and time of a drug dosing event. 

With the landscape of smart packaging growing rapidly, the process of selecting and qualifying the right combination of vendors and their solutions can become a lengthy endeavor, often stretching to almost nine months. To address this concern, Thermo Fisher offers a pre-qualified portfolio , simplifying the adoption of these innovative solutions into the clinical supply chain. Now, more than ever, the merging of technology and medication adherence management promises an enhanced, patient-centric trial experience, ensuring that adherence to study protocols is not compromised.

Recently, Thermo Fisher Scientific’s John Musaus, head of medication adherence and biomarker measurement, shed light on the data-quality implications of smart packaging as well as options for seamlessly integrating these solutions into clinical trials.

Q: Why is medication adherence so pivotal in clinical trials?

A: Another way to think about medication adherence is to think in terms of patients taking enough medication doses to be exposed to the study drug as planned by the clinical trial designers when they created the trial protocol. 

Research has shown that of every hundred trial participants, four do not initiate a study drug and 10-12% do not take their medication each study day. In long-term studies, after one year, almost 40% of trial participants have stopped taking their medication. When patients don't follow the prescribed dosing regimen, it reduces their overall exposure to the study drug making it more challenging to statistically separate from placebo and prove the efficacy of the drug.  From a trial management perspective, medication adherence is at the heart of ensuring data quality. Non-adherence can lead to the loss of statistical power. To compensate for this, more patients must be added to the study. The ripple effect of requiring more patients in a study leads to prolonged recruitment, longer time to market access, and higher costs.

Q: How do adherence measurement solutions such as smart packaging ensure data quality in clinical trials?

A: The primary methods to measure medication adherence in clinical trials are pill counts and diaries.  These are popular methods because they are easy to execute and are low cost. However, both measurement techniques have been shown to be fraught with bias, making them unreliable. In addition, they often don’t capture enough detail for drug developers to get the full picture of patient dosing. For instance, the drug count technique only provides an aggregate number of doses taken, but it can’t inform researchers how those doses were taken. This is important because the specifics surrounding how those doses are taken can have a direct impact on a patient reaching a healthy outcome.

New digital adherence measurement techniques such as smart packaging use passive measurement methods which increase the reliability of the collected data dramatically. When patients retrieve and take their medicine, smart packages and smart devices automatically time stamp the date and time of the dosing event. This can be measured by a tablet being pushed through a blister card, an autoinjector being activated, the disposal of a needle in a sharps container, or other actions. Passive measurement techniques also produce more data points, thus a much richer data set, so patterns of dosing behaviors can be easily detected and properly managed through interventions and other communication techniques.

Q: What are some of the most valuable smart packaging capabilities and solutions available for integration into clinical trials?

A: There are a number of innovative technologies and capabilities that can meet the needs of most drug delivery formats. For example, Thermo Fisher maintains a portfolio of adherence measurement solutions for oral solid tablets, vials and pre-filled syringes, and auto-injectors. In addition, there are techniques for inhalers, pumps, and sprayers as well as dermatology and optical solutions.

Q: Who stands to benefit the most from smart packaging solutions? 

A: The most valuable aspect of passive, digital adherence measurement solutions is the adherence data collected. Reliable patient drug dosing histories can be used across drug development organizations.  Examples include measuring and managing better dosing behaviors to increase patient exposure to study drug; using the data to adjudicate PK/PD models at the patient level; and managing drug accountability programs reducing the requirement for on-site visits.

The most important beneficiaries are the patients, both at the population and individual levels. Trial outcomes derived from accurate and reliable adherence data translates into safer, more effective therapies. Additionally, smart packaging can minimize the risk of medication mishandling or misuse through features such as tamper-evidence and real-time tracking. And for patients whose trial medications have specific storage requirements, smart packaging can monitor environmental factors such as temperature and humidity, generating alerts if conditions become unsuitable. Finally, smart packaging also has the potential to improve the overall patient experience by reducing the participation burden, in that patients no longer need to maintain a diary of their medication dosing events.

Q: What is involved in choosing the right adherence measurement solution to meet the specific needs of each clinical trial?

A: Choosing the right adherence measurement solution for clinical trials requires a combination of understanding the trial's protocol needs, partnering with the right vendors, rigorous testing, and continuous monitoring. In many cases the managers of the clinical trial will need to conduct a trade-off analysis to select the most appropriate solution based on the factors that matter most for a specific trial protocol. Tradeoff criteria often center around how fast and how often the study team needs to analyze adherence data, the burden on the patient to use the solution, and budget constraints.  On occasion, regional infrastructure requirements may play a role in solution selection.

Q: The smart packaging solutions offered by Thermo Fisher Scientific are described as pre-qualified. What does this mean and why does that matter?

A: It means that all the adherence measurement solutions Thermo Fisher offers in our portfolio of options go through a rigorous QA qualification to ensure each solution meets the requirements for GMP and GCP certification. In addition, we test each solution for reliability and usability. With the increased development and deployment of digital solutions targeted for use in clinical trials, many sponsor companies are struggling to keep up with vendor qualification– often taking as long as 6-8 months to complete their qualification process. Having a portfolio of pre-qualified solutions allows study teams the chance to adopt and use adherence measurement solutions without affecting their timeline for study initiation.

Q: As a CDMO partner, Thermo Fisher is committed to the concept of holistic quality. How does the company’s adherence measurement portfolio of solutions fit into this ideal?

A: At its core, holistic quality in a CDMO relationship involves looking beyond just the product. It's about considering the entire experience and process, from development and manufacturing to delivery and administration. This means ensuring that all stages of the process are optimized for both efficiency and efficacy, guaranteeing a seamless and high-quality experience for our customers. Smart packaging is a testament to our commitment to holistic quality. It's not just about containing the medication, but about making sure that medication is used as intended. With features that can remind patients to take their medication, track dosage, or even report data in real-time, smart packaging becomes an extension of the clinical trial experience, ensuring the integrity and success of the trial.