PO Q1 2021 - 30

CLINICAL TRIALS

Digital Adherence: A Modern
Solution to an Age-Old Problem
Bernard Vrijens, PhD
Scientific Lead
AARDEX Group
Non-adherence to medication in general medical practice is a
long-standing problem, and its impact on health outcomes has
been well documented.

many cases lifechanging for the people who take them, biological
drugs, which are made from living organisms, are also extremely
expensive to develop.

What is less readily explored, however, is its effect on clinical trials.
Across all studies, therapy areas and stages of development, around
50% of participants admit they do not adhere to the dosing regime
set out in the protocol and around 30% of subjects in Phase III studies
are non-adherent by day 100.

Tackling the costly consequences of non-adherence, it could be
argued, has never been so important.

Study Power Drain
We all know the importance of study power during clinical trial
design. The higher the study power, the higher the probability of
detecting a drug's true effect. A higher statistical power increases the
chances of success, enables more informed go/no go decisions, and
shortens the time to market.

The impact of this lack of adherence can be huge. From underestimated
drug efficacy and delays in the approval of investigational products,
to increases in development costs and lost revenues, non-adherence
is an issue that costs sponsors money and reduces patient access.
Fortunately, the technology and the expertise needed to take
control of medication compliance not only exists but is relatively
easy to implement.

It's a complex equation that depends on three factors: the effect size
of the drug itself, the variability in drug response, and the sample size.
In short, the sample size must be large enough to show the maximum
effect size with the lowest variability.

Getting to the Root of the Problem
Barriers to adherence are both multiple and complex. People may
have swallowing difficulties, and find it psychically challenging to
take as many tablets as a protocol calls for. Others may be concerned
about side effects, or simply forget to take their medicine at the
right time.

But when subjects do not take their medication as directed, it
decreases effect size and increases variability. This, in turn, drains
study power. The exponential relationship between non-adherence
and sample size means that any decrease in adherence must be met
with an expensive, labor-intensive increase in study participants if
power is to be maintained.

It's a problem that extends across delivery routes and therapy areas,
but some spaces are more affected than others.

Non-adherence, then, has a direct effect on the cost and duration of
clinical trials, and can slash return on investment (ROI).

In trials of self-injectable molecules delivered by pre-filled syringes
(PFS), for example, patients face unique challenges. They may find it
hard to handle the device, or they may experience needle phobia.

Overcoming this challenge calls for a modern solution that is adapted
to the specifics of the field.

Digital Transformation

While autoinjectors have been introduced to overcome many
common usability issues in day-to-day care, this has not yet been
extended to clinical development - despite the huge increase in PFSdelivered drugs currently in development.

Digital adherence monitoring gives trial leaders an invaluable insight
into adherence levels. It allows them to identify and correct problems
before they can drain study power and interfere with study results.

The PFS market, fuelled by the growing popularity of biological
agents for the treatment of long-term diseases, is expected to be
worth $9.7B by 2025. But while they are highly efficacious, and, in
Pharmaceutical Outsourcing |

Non-digital methods, such as pill counting or patient self-report
diaries, are biased and not sensitive enough to detect non-adherence.
Data-driven digital solutions are different.
30

| January/February/March 2021



PO Q1 2021

Table of Contents for the Digital Edition of PO Q1 2021

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