VIEWPOINT

2023

THE FUTURE OF
PHARMACOVIGIL ANCE

The right positioning of pharmacovigilance

is a key enabler in drug development

AUTHORS

While assessing the safety and efficacy of medicines Dr. Sabine Jeck-Thole, MD
is the bedrock in drug research, vaccine development
Ben Enejo
during the COVID-19 pandemic highlighted the
changes in the types of medicines developed today
and the stakeholder management required for
successful adoption. Enabled by new treatment
paradigms, digital transformation, advanced
technology applications, data availability, and
the patient-centric focus, the changing ecosystem
requires new capabilities in assessing the safety of
medicines and managing the new entities at play.
This Viewpoint explores strategies for innovative
companies to excel with the industry shift, focusing
on pharmacovigilance (PV) as a strategic advantage.
 VIEWPOINT ARTHUR D. LITTLE

PHARMACOVIGIL ANCE HAS What is clear in today’s drug development process

NE VER BEEN MORE CRITICAL is that the positive treatment effects — the

IN DRUG DE VELOPMENT “efficacy” — tend to prevail in the discussion,

while drug “safety” may not always be seen as
The drive for safe and effective medicines has a strategic input but more of an obligation.
accelerated since the thalidomide tragedy in the The regulation-mandated obligations to report
early 1960s and has led to the implementation adverse events (AEs) and adverse drug reactions
of a variety of disciplines to ensure the public is (ADRs) mean PV is often regarded as a “data
protected (see Figure 1). From a health authority collecting and submitting” office — a post-
(HA) perspective, many regulations have been box-like team. Aligned with this perceived view,
introduced, with dedicated agencies overseeing PV departments have developed operational
drug approvals, licensing, and use. For drug excellence regarding case processing and
developers, structures, standards, and processes reporting (expedited and aggregated alike).
have been put in place to ensure they comply They frequently employ external service
with the applicable regulations and ethical values. providers as well as smart IT solutions aimed
The use of medicines and vaccines must protect at touchless case handling and cost efficiency.
patients and safeguard public health. This operational focus is frequently reflected
in and maintained by organizational structures,
However, the controversial discussion
capabilities, and resources, as well as the
surrounding the safety of the COVID-19 vaccines
emphasis on efficacy during drug development.
moved PV (the science and activities related to
adverse effects of medicines and vaccines) into
the general consciousness to an extent never PV AUTOMATION ALONE
before seen. This discussion also put PV in the WILL NOT SUS TAIN
middle of a heated, often political, debate and ECOSYS TEM CHANGES
contributed to the negative sentiment toward
The global COVID-19 pandemic identified the need
some COVID-19 vaccines and the refusal by
for a different approach to science and healthcare
a portion of society to take those vaccines.
Figure 1. The pharmacovigilance timeline — one that includes an unmistakable call for the

Figure 1. The pharmacovigilance timeline appropriate use of PV scientific excellence that

considers the expected multifold changes that

Thalidomide crisis are occurring in the types of medicines being

1960s
developed and/or the way they are developed
Adverse event reporting requirements

Drug monitoring programs

and approved. These transformations, be it in
drug modalities (e.g., mRNA-based compounds),

Increased health authority guidelines digitalization, innovative clinical trial design, or

1980s
Emerging PV functions in pharma companies complexities in the regulatory pathways, all point
to the fact that PV’s operational excellence and
focus on automation of case processing will not
be sufficient in the future.
Safety guidelines and legislation
2010s
PV functions shift toward cost center model The call to review PV’s value proposition at
this turning point is of special importance for
Rapid ecosystem change established companies that are undergoing major
2020s
COVID-19 pandemic catalyst to evolution transformations and for the rising stars that jump
from pure research to marketing drugs in almost
no time.
Future PV

Source: Arthur D. Little

ource: Arthur D. Little

THE FUTURE OF PHARMACOVIGILANCE 2

 VIEWPOINT ARTHUR D. LITTLE

DISRUP TORS HERE TO S TAY The COVID-19 pandemic accelerated the use of
transformative medicines and especially mRNA
While COVID-19 vaccine development raised technology. While addressing unmet patient
legitimate questions, we believe that it is needs is exciting and rewarding, the novel
emblematic of the disruptions that are driving treatments, such as chimeric antigen receptor
the  ecosystem change. As with any seismic (CAR)-T cell and curative gene therapies, require
shift in an industry, businesses that are aware, a transformation of PV expertise compared to
ready, and equipped for the changes will be best the established, chemical-synthesized small
positioned to thrive. For PV, organizations will molecule drugs.
have to address the following three areas.
2. Digitalization & access to more & new data
1. New treatment paradigms
Electronic health records, the Internet of
Precision medicine (also referred to as Things, and medical devices linked to the cloud
personalized treatment or targeted therapies) enable the generation of an unprecedented and
contrasts significantly with the traditional one- astronomically high amount of data. Devices,
approach-fits-all model. It aims at improving such as wearables and apps, are increasingly
health outcomes by utilizing genomic, proteomic, used to allow participation in clinical trials,
metabolomic, and other biomarkers. Genotyping monitor patient progress, and collect and handle
is described in some labels as a predictive safety data. Digital technology can provide access to
measure (e.g., carbamazepine and abacavir), but routine and additional risk-mitigation activities
pharmacogenomics is not broadly introduced in in clinical practice (e.g., package inserts).
the PV routine. There are only a limited number However, various areas require clarification,
of randomized clinical trials that demonstrate including the following questions:
the advantages of drug selection and dose
adoption for the individual patient in reaching
- What are the consequences for PV regarding
the information coming from, for example,
the drug’s optimal benefit-risk ratio. For various
an activity tracker?
reasons, the few trials that exist do not prove the
predictability of the biomarker for recommending - Is there an obligation for a pharmaceutical
genotype-guided treatment. company to collect, process, and report
“accidental information”? And, if so, what
would be the added value for a product safety
WHILE ADDRESSING assessment using that data?
UNME T PATIENT NEEDS
- Is there an adverse event reporter in data
IS E XCITING AND collected from social media?
REWARDING, THE NOVEL Digital symptom management using smart tools
TRE ATMENTS REQUIRE may improve patient safety, quality of life, and
A TR ANSFORMATION outcome. Moreover, these systems could have
the functionality to capture and analyze real-
OF PV E XPERTISE
world data. Various workstreams at the European
Medicines Agency (EMA), the US Food and Drug
Over the past three decades, biologics have Administration (FDA), and the US National
revolutionized drug development. These mostly Institutes of Health (NIH) are also working with
high-cost compounds offer new therapeutic experts from epidemiology, statistics, and
options for several chronic and sometimes computer science, among others, on strategies
life-threatening diseases (e.g., in oncology, for the effective management and analyses of
immunology, and various rare diseases). these data streams. At present, there is a lack of

THE FUTURE OF PHARMACOVIGILANCE 3

 VIEWPOINT ARTHUR D. LITTLE

clarity regarding the usage and acceptance of REINVENTING

real-world data and patient-reported outcomes PHARMACOVIGIL ANCE
within regulations.
In response to the changing ecosystem of drug
With the digital and technological advances
development and new treatment paradigms, we
alongside the potential regulatory grey zones,
believe the way forward for drug developers is
PV organizations must now prioritize their strategy
a shift to a forward-looking and empowered PV
for handling and using the inbound digitally enabled
operating model. This requires various building
data, both from trials and post-marketing.
blocks, as outlined below.

3. The shift to “real” patient-centricity

Early PV involvement with new and/or
It may sound provocative, but PV departments digital-enabled projects
have tended to consider HAs as their key partners
The importance of patient safety mandates a
rather than the patients. Understandably, this has
leading role for PV science to enable the smart
been due to the strong focus on compliance and
use of experts and personnel and in preventing
the perception of HAs as the exclusive advocates
data disasters. This definitively includes activities
of patients. However, there is now a shift to
conducted under the umbrella of market research
putting the “real” patient first to achieve the
programs and patient support programs that
best  experience and outcome for them. This
have increasingly gone digital as well as the use
poses challenges for PV organizations, such as:
of other real-world data.
- Thus far there is no established definition
of patient-centricity or a general standard
framework for patient-centric approaches.
P V U N I T S W I L L H AV E
The heterogenicity of terms hinders the
TO INJECT NEW
identification of PV’s role in discussions with
research and development, commercial, legal, C A PA B I L I T I E S T O B E
regulatory affairs, and so on, on the essential ABLE TO GUIDE THE
role PV can play for patient-centered- BUSINESS
outcome delivery.

- Proactive, fact-oriented, and consistent

communication with understandable The shift in gear required for the future of
messages regarding product safety and risks health is one where PV teams are at the
plays a key role in gaining patients’ confidence forefront of conducting new technology and
in drug treatment and maintaining treatment data type assessment instead of the current
compliance. Yet PV is not generally at the reactive model. PV units will have to inject new
forefront of these communications. The capabilities — from machine learning specialists
COVID-19 pandemic revealed many examples to health technology assessment experts — to be
of the impact of miscommunications on able to guide the business on new digital-enabled
vaccine safety. strategies and projects.

Various companies have recently added “patient Furthermore, PV units will need to develop or
safety” to their PV department name to reflect contribute to a framework and training to ensure
the commitment to patient involvement in that the way a company is using advanced tools
medical decision making, their preferences, and and digitalization adds value to PV topics and is
perspectives. This is a first step and a move in the compliant with respective regulations.
right direction.

THE FUTURE OF PHARMACOVIGILANCE 4

 VIEWPOINT ARTHUR D. LITTLE

Accelerating “real” patient-centricity New talent acquisition

As stated earlier, effective communication Novel therapies, advanced therapy medicinal

regarding product safety and risks plays a key products (ATMPs), and new methods in drug
role in enabling patients’ confidence in new development require new talent in PV with
drug therapies and in maintaining treatment the qualifications and expertise needed to
compliance. Effective communication requires define the risk profile of the newer, highly
PV leadership and PV resources, proactive individualized treatments, such as CAR-T cell
planning, and intense collaboration with internal therapy. Knowledge in pharmacogenomics and
and external partners, as well as the willingness clinical immuno-safety, aiming for high-quality
and skills for mutual understanding. standards, ensuring reliable information for
advances in signal detection, and identifying the
Future PV will require dedicated sub-functions
frequency of ADRs in overall low patient numbers
with the sole responsibility of direct engagement
can be challenging. Multi-stakeholder dialogue is
with patients and patient groups through their
a crucial tool in guiding these new therapies, and
preferred communication channels to collate
PV should assume accountability for navigating
questions and concerns and to more effectively
the less worn paths. Companies will have to
translate safety-related information to the
acquire talent with the right expertise or invest
layperson. This will involve new ways of working
in developing these internally.
internally as well as increased engagement with
functions like patient advocacy, medical affairs,
External partnerships
medical communications, and commercial to
ensure a holistic view of the end customer. Challenges and opportunities regarding

Furthermore, the safety profiling of medicinal innovative and/or complex trial designs,

products and the evaluation of the benefit-risk accelerated patient recruitment, regulatory fast-

balance historically have been conducted with track designations, public-private partnerships,

information that does not represent a diverse and so on, can only be addressed by multi-

population. Underrepresented groups lead stakeholder partnering. Relevant partners should

to knowledge gaps regarding safety between come together from the pharmaceutical industry,

trials and real-world scenarios with an impact academia, HAs, and patient organizations.

on confidence in medicinal products and latent These new models work best when roles and

unforeseen consequences for the impacted responsibilities are clearly detailed and mutually

patient group (see Figure 2). PV will have to play a agreed upon, such as in a PV agreement, and
Figure 2. Accrual ofrole
significant minorities to
in closing the gaps clinical
in trial diversity. trials
when PV has the opportunity to contribute to
public consultations.

Figure 2. Accrual of minorities to clinical trials

2% 2% 2% 3% 3% 5% 4%
14% 16% 17% 19% 21% Across all trial
22% 25%
phases (1999–2019)

84% 82% 81% 78% 77% 73% 71%

1999-2001 2002-2004 2005-2007 2008-2010 2011-2013 2014-2016 2017-2019

Majority Minority (subsets like Black/African Americans, Hispanics, Asians) Not reported

Source: Arthur D. Little; National Cancer Institute, 2020

THE FUTURE OF PHARMACOVIGILANCE 5

 VIEWPOINT ARTHUR D. LITTLE

CONCLUSION

ENSURING SUCCESS
WITH PV

PV HAS A CRUCIAL ROLE IN THE

E N V I R O N M E N T O F A C C E L E R AT E D
T R A N S F O R M AT I O N S

Giving patients access to game-changing, high-quality, and

safe treatments within the shortest possible time frame is a
pharmaceutical industry mandate. PV has a crucial role in this
environment of accelerated transformations. PV departments and
associates should be tasked to demonstrate the added value that
they bring to drug development and marketed products, beyond
pure data handling and operational proficiency:

1 Give PV a seat on the leadership team with a clear mandate

to provide input into the strategy of new treatment paradigms,
accelerated trial designs, and new marketing concepts before
commencing clinical trials.

2 Set up a global PV organization with strong local input

and constant interdepartmental exchange, anchored high
in a company’s hierarchy.

3 Establish measures to attract, build, and retain new PV talent.

Also, assign appropriate resources with a clear mandate to build
the required capability for the new ecosystem.

4 Drive a culture where all employees, from top to bottom,

share a compliant PV system and PV compliance is a company-
wide task that does not stop at the PV department door.

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 VIEWPOINT ARTHUR D. LITTLE

5 Involve PV very early in the company’s digital projects, not

to add bureaucracy but to make the best use of the activities
and to guarantee compliance.

6 Give PV science a leading role in initiatives and workstreams,

looking at how to generate additional, meaningful, and compliant
data from existing information.

7 Train PV experts to efficiently communicate the facts

regarding product safety and contribute to answering questions
on the benefit-risk of medicinal products and vaccines.

8 Create networks with other drug developers, academia, and

HAs to benefit from concerted actions and learn from each other.

Increasing reliance on PV expertise for patient and product safety

topics throughout clinical development, at filing, at product launch,
and throughout the lifecycle of a medicine gives PV higher visibility
and an opportunity to add value. PV must leave the post-box silo and
the pure focus on operational excellence and instead demonstrate
accountability and show it is prepared to address the needs of the
different treatment paradigms, the changing healthcare system,
and the evolving science landscape. A strong and well-anchored
PV department gives a company the flexibility to adapt to challenges
and take on future projects.

THE FUTURE OF PHARMACOVIGILANCE 7

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