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13 Collaborative Approaches toEstablishing andImplementing Pharmacovigilance Systems
317
55. Rolfes L, van Hunsel F, van der Linden L, Taxis K,
van Puijenbroek E.The quality of clinical information in adverse drug reaction reports by patients and
healthcare professionals: a retrospective comparative
analysis. Drug Saf. 2017;40(7):607–14.
56. Faulkner SD, Sayuri S, Pakarinen C.Understanding
multi-stakeholder needs, preferences, and expectations to dene effective practices and processes
of patient engagement in medicine development: a mixed- methods study. Health Expect.
2021;24:601–16.
57. Bahri P, Pariente A. Systematising pharmacovigilance engagement of patients, healthcare professionals and regulators: a practical decision guide derived
from the international risk governance framework
for engagement events and discourse. Drug Saf.
2021;44(11):1193–208.
58. Cavaller-Bellaubi M, Faulkner SD, Teixeira B, et al.
Sustaining meaningful patient engagement across the
lifecycle of medicines: a roadmap for action. Ther
Innov Regul Sci. 2021;55:936–53.
59. CIOMS Working Group XI Report. Patient involvement in the development, regulation, and safe use of
medicines; 2022. https://doi.org/10.56759/iiew8982.
60. Edwards B, Gloor CA, Toussaint F, Guan C, Furniss
D.Human factors: the pharmaceutical supply chain as
a complex sociotechnical system. Int J Qual Health
Care. 2021;32(Suppl. 1):56–8.
61. Evans SJW.Pharmacovigilance: a science or elding
emergencies? Curr Perspect Future Direct Med Stat.
2000;19(23):3199–209.
62. Caro-Rojas A.Patient safety context and its advances
in Latin America chapter. In: Papale RM, editor.
Manual of good pharmacovigilance practices, Latin
American edition.; ISBN 978-987-46704-2-7; 2018a.
p.771–8.
63. Edwards B. Best safety practices now and in the
future. In: Pharmacovigilance: critique and ways for-
ward. Switzerland: ADIS; 2017. p.35–48. (Chapter
5).
64. Edwards B, Olsen AK, Whalen MD, Gold
MJ.Guiding principles of safety as a basis for developing a pharmaceutical safety culture. Curr Drug Saf.
2007;2:135–9.
65. Kar N, Barreto S, Chandavarkar R. Clozapine
monitoring in clinical practice: beyond the mandatory requirement. Clin Psychopharmacol Neurosci.
2016;14(4):323–9.
66. Quigley EMM. Cisapride: what can we learn from
the rise and fall of a prokinetic? J Digest Dis.
2011;12:147–56.
Further Reading
Andrews EB, Moore N, editors. Mann’s pharmacovigi-
lance. 3rd ed. Wiley Blackwell; 2014.
Eu2P: European training programme in Pharmacovig-
ilance and Pharmacoepidemiology https://www.eu2p.
org/ (accessed 25 Mar 2023).
Good Pharmacovigilance Practices. https://www.ema.
europa.eu/en/human- regulatory/post- authorisation/
pharmacovigilance/good- pharmacovigilancepractices (accessed 23 Feb 2023).
ICH Efcacy Guidelines. https://www.ich.org/page/
efcacy- guidelines (accessed 25 Mar 2023).
Medicines and Healthcare Product Agency Yellow
Card reporting site https://yellowcard.mhra.gov.uk/)
(accessed 25 Mar 2023).
Prescribing Safety Assessment. https://prescribingsafe-
tyassessment.ac.uk/ (accessed 25 Mar 2023).
Talbot J, Aronson JK, editors. Stephens’ detection and
evaluation of adverse drug reactions: principles and
practice. 6th ed. John Wiley & Sons Ltd.; 2012.
Ethics inPharmacovigilance
AlisonThompson andAnaKomparic
14
Abstract
Healthcare practitioners play a vital role in
facilitating effective and ethical pharmacovigilance, as well as in translating evidence generated through pharmacovigilance activities
into clinical practice to improve the care of
patients and to improve population health.
Physicians, nurses, dentists, pharmacists, and
other health practitioners have ethical obligations stemming from their professional obligations to act in their patients’ best interests,
to protect and promote the public good, and to
maintain their professional competence. In
turn, these obligations give rise to a host of
ethical principles and considerations related to
pharmacovigilance and the safe use of pharmaceuticals. This chapter outlines several of
these key principles and considerations,
including the duciary duty, the duty to protect the public from harm, the duty to maintain
professional competence, privacy, consent,
disclosure, equity, trust, inclusiveness, the
duty to report, scientic integrity, the duty to
A. Thompson (*)
Leslie Dan Faculty of Pharmacy & Dalla Lana
School of Public Health, University of Toronto,
Toronto, ON, Canada
e-mail: a.thompson@utoronto.ca
A. Komparic
Dalla Lana School of Public Health, University of
Toronto, Toronto, ON, Canada
use the highest quality evidence, and conicts
of interest.
Keywords
Professional ethics · Bioethics · Public health
ethics · Clinical ethics · Pharmacovigilance
ethics · Drug safety · Patient engagement ·
Equity · Conict of interest · Integrity ·
Nocebo effect
Learning Objectives
• To identify ethical concepts of relevance to
pharmacovigilance activities.
• To analyze how professional ethics duties
intersect with pharmacovigilance activities.
• To understand how public health ethics is rel-
evant to pharmacovigilance and drug use.
• To understand that scientic integrity is an
ethical issue related to evidence used in drug
safety in clinical practice and drug regulation.
Key Points
• Pharmacovigilance relies on the ethical
actions of researchers, healthcare practitioners, industry, patients, and the public; it is not enough to rely on evidence
alone when making clinical decisions.
• Healthcare practitioners have ethical
duties to patients and to the public that
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
J. Jose et al. (eds.), Principles and Practice of Pharmacovigilance and Drug Safety,
https://doi.org/10.1007/978-3-031-51089-2_14
319
320
guide pharmacovigilance activities, but
healthcare practitioners can encounter
ethical dilemmas when faced with conicting ethical duties, or when legal
duties conict with ethical duties.
• Ethical practice requires ethical deliberations with other professionals,
patients, and society more broadly
and requires sensitivity to cultural
differences.
1 Introduction
Healthcare practitioners play a crucial role in
pharmacovigilance and are responsible for identifying and minimizing the risks to patients posed
by pharmaceuticals. Increasingly, patients are
being asked to help identify potential adverse
events that result from their use of pharmaceuticals. There are several ethical considerations pertaining to pharmacovigilance in the context of
clinical practice, and this chapter will provide an
overview and discussion of the most salient
issues facing healthcare practitioners.
While primarily conceived of as a scientic
endeavor, pharmacovigilance relies on the ethical
actions of researchers, healthcare practitioners,
industry, patients, and the public to generate reliable and comprehensive data to keep people safe.
And while causation assessment is grounded in
science, without taking patients seriously about
their experiences with drugs and biologics, we
cannot hope to understand the risk/benet prole
of a pharmaceutical product. Recent efforts to
A. Thompson and A. Komparic
engage patients more actively and broadly in
potential adverse event reporting and clinical trial
design signies an ethical shift toward valuing
the perspectives of patients as partners in pharmacovigilance, and toward a more collaborative
model of clinical practice when it comes to pharmaceutical care.
In this chapter, we will explore the ethical
landscape in clinical practice with the hope that
healthcare practitioners can further explore these
issues in a constructive and fair dialogue with
colleagues, patients, and the broader community
within which they practice. Cultural differences
in values can also give rise to different framings
of ethical issues, so we do not claim that this
chapter is the nal word on ethical issues in pharmacovigilance, but rather the start of a dialogue
on these issues that must be broadened.
As ethical dilemmas frequently involve tensions between professional obligations or ethical principles, the principles and ethical
considerations provided here are meant to
inform readers about ethical issues that can arise
in practice. However, only through a process of
ethical deliberation can healthcare practitioners
decide on the best course of action. This will
often mean choosing to act on one value or consideration over another. The process of ethical
discernment may involve discussions with colleagues and patients, and subsequent actions
need to be justied based on ethical arguments
that most people would agree are reasonable,
even if they do not agree with the substantive
decision itself.
The ethical considerations related to pharmacovigilance are listed in Fig.14.1 and are discussed
in detail in the remaining part of the chapter.
Ethical Considerations for Pharmacovigilance
Integrity is important for the validity of the evidence used to inform prescribing and for building patient and public trust
SCIENTIFIC INTEGRITY
14 Ethics inPharmacovigilance
321
PROFESSIONAL ETHICS
PRIVACY
CONSENT
DISCLOSURE
EQUITY
TRUST
INCLUSIVENESS
DUTY TO REPORT
Fig. 14.1 Ethical principles and considerations for pharmacovigilance
2 Professional Ethics
Healthcare providers are guided by codes of ethics that put patient welfare and public health at the centre of their practice
Respect for patient confidentiality is rooted in their right to privacy
Patient consent for release of personal health information or for par ticipation in pharmacovigilance studies is warranted
Healthcare practitioners often have formal disclosure responsibilities when medication errors or violations occur
Inequitable representation in clinical trial design and big data sets can impact real world drug safety and effectiveness
Pharmacovigilance can help bolster public trust, but it also relies on the willing participation of a trusting public
It is important to include diverse patient perspectives on drug safety and effectiveness in pharmacovigilance activities
This duty is grounded in the need to protect the public from harm by increasing collection of safety and effectiveness data
ethical obligations often extend beyond the minimum legal standards that they must abide by in
Healthcare practitioners involved in the development, supply, prescribing, administration, and
management of pharmaceuticals are members of
healthcare professions. Professions are often
characterized as being in an implicit contract
with society [1]. In other words, healthcare professionals are expected to commit to uphold the
duciary duty—that is, to act in their patients’ (or
clients’) best interests—and to protect and promote the public good, as well as to maintain professional competence. In return, professions are
granted certain privileges such as professional
autonomy, meaning that the profession is responsible for determining its members’ standards of
practice and that professionals can exercise their
independent, professional judgment in decisionmaking, and self-regulation. This allows professions to oversee the education, licensing, and
disciplining of their members’ conduct [1–4].
The ethical obligations that healthcare professionals must abide by with respect to their
patients and the public at large are articulated in a
profession’s code of ethics and underpin the more
detailed rules and standards outlined in the laws,
regulations, standards, by-laws, and guidelines
that govern clinical practice. A professional’s
the jurisdiction where they practice.
Upholding the duciary duty and promoting
the public good are vital for building and maintaining the trust of patients and the public at large
[4]. Trust is central to an effective therapeutic
alliance and to an open patient–clinician relationship. In the absence of trust, patients may be
reluctant to seek or follow the advice of healthcare practitioners, or to openly raise concerns
with healthcare practitioners, including related to
their use of pharmaceuticals and any resulting
adverse events [5]. As a result, mistrust or a lack
of trust can hamper pharmacovigilance efforts
and harm patients.
In addition to being grounded in professional
ethics, effective pharmacovigilance in clinical
practice requires inter-professionalism, since
pharmaceutical prescribing and management
often involves inter-professional teams.
Accordingly, professionals must make a concerted effort to work with colleagues across the
multiple professions that comprise a patient’s
circle of care to facilitate safe and effective treatment and to address the ethical and professional
issues concerning pharmaceutical use that they
may encounter in practice.
322
A. Thompson and A. Komparic
Many of the ethical considerations and principles related to pharmacovigilance that are outlined in this chapter can be understood as being
grounded in, or supportive of, healthcare practitioners’ fundamental ethical obligations to act in
the patients’ best interests and to protect and promote public good. A wider ethics discussion
about the relationship between those directly
involved in healthcare delivery and those who are
in the commercial pharmaceutical industry is out
of scope but is touched on in several places in this
chapter. However, the inuence of industry on
prescribing habits and the scholarly literature is
not insignicant, and this is important to understand for a fuller picture of society’s pharmacovigilance system [6–8].
3 Privacy
The ethical obligation to keep a patient’s health
information condential is based on the principle
of respect for patient privacy. Most adverse event
reporting systems do not require the reporting
clinician to violate patient privacy, such as the
anonymous reporting in the UK through the government’s Yellow Card scheme. However, when
identifying information is required for reporting,
patients should be asked for their permission.
Having enough information to identify a
patient in a report is essential for follow-up for
outcome and to help prevent duplication, and this
should be explained to the patient. The expectation that patients have around condentially must
be balanced with the need to protect the public, or
other patients, from harm. Most codes of professional ethics include an articulation of responsibility in some form to the broader public, whether
that be in the form of a responsibility to maintain
public trust in their respective profession, or in a
duty to warn, or a duty to care. Many jurisdictions will have laws articulating when a patient’s
privacy may or ought to be breached to protect
others, or to report abuse of pharmaceuticals. Not
many, however, have a clear articulation of when
to prioritize the public’s health over patient condentiality outside of the reporting of infectious
diseases. It could be argued, however, that the
duty to report adverse drug events trumps a
patient’s right to privacy if and only if there is no
way to report the event that can maintain patient
condentiality—for example, in the case where
the population of drug users is so small that it is
likely that the patient could be identied, as can
happen with orphan medicines, or where identifying information about the patient is crucial to
reporting the adverse event.
The digital transformation of pharmacovigilance is aimed at improving adverse event reporting and safety signal identication, but the
protection of private health information will
remain central to the ethical use of digital technologies. Data sources include voluntary adverse
event reporting applications for mobile devices,
mobile health technologies and applications,
internet-based surveys of patient experiences with
drugs, and machine learning algorithms that aid in
the identication of safety signals by mining
sources of patient information such as electronic
health records, health information technologies,
and pharmacovigilance database systems.
Commercial entities, insurance companies, and
even law enforcement and immigration authorities are all potential parties who could have an
interest in these data. Protecting privacy will not
only encourage reporting, but it will also ensure
that these data are not used in ways that might
violate dignity or disadvantage individuals and/or
groups of people who may already be disadvantaged or stigmatized. Private, for-prot, third parties are often hired to manage and collect these
data [9], which raises issues around data privacy,
especially in light of healthcare data breaches. A
recent study revealed that “hacking/IT incidents
are the most prevalent forms of attack behind
healthcare data breaches, followed by unauthorized internal disclosures” and that healthcare data
are deemed highly valuable, with the result that
“the frequency of healthcare data breaches, magnitude of exposed records, and nancial losses
due to breached records are increasing rapidly”
[10]. Balancing the promise of digital technologies to improve pharmacovigilance activities with
vigilance over patient privacy and the appropriate
uses of these data sources to improve drug safety
and effectiveness will require that patients be not
Approaches to Informed Consent in Data-Generating Activities
e
ticular
be
clinical
patient
ntial
is
e major practical
14 Ethics inPharmacovigilance
323
just informed of the risks, but that they are actively
engaged in conversations around privacy and digital health technologies.
4 Consent
Informed consent is a fundamental ethical principle and is grounded in the principle of respect
for persons—that is respect for patients and/or
research participants—and their right to autonomy or self-determination. Consent from patients
for treatment or research participation should be
considered on a spectrum from no consent to
fully informed consent (Fig.14.2), whichraises
some challenging ethical issues related to reporting adverse events spontaneously without jeopardy and to pharmacovigilance research.
In clinical practice, patients must consent to
treatment, and this typically requires the full disclosure of the risks and benets associated with a
course of treatment. Where risks are unknown or
there is uncertainty about benet, this ought to be
disclosed to patients. Concerns that sharing information with patients about the possible side
effects of medication would bias patient reports of
side effects (and thereby taint pharmacovigilance
studies that include patient reported side effects)
do not seem to have been born out in the literature
[11]. There is some concern that full disclosure to
patients might “manifestas nocebo- effect,” where
an adverse event results from the belief that an
intervention will cause harm, but that “concerns
about the undesirable effects should not deter the
active involvement of patients in pharmacovigilance activities” [11]. The tension for healthcare
practitioners is that in respecting patient autonomy and seeking informed consent—which normally entails full disclosure of possible side
effects—the clinician is actually causing harm
[12]. For public health, there are also signicant
costs related to subsequent clinical management
of nocebo effects in addition to the potential
impact of this effect on adverse event reporting
[13]. However, one proposal for mitigating the
possible harms from full disclosure of side effects
is to seek to attain “contextualized informed consent” [12], where nocebogenic information is not
disclosed to the patient. Vague, nonspecic side
effects like fatigue, dizziness, or nausea are more
likely than drug-specic side effects to contribute
to a nocebo effect. Drug-specic side effects
should be disclosed to patients, it is argued,
because “they may result in more debilitating
symptoms/conditions and thus may be more
important for the patient’s full informed consent”
[12] as well as for their decision-making about
whether or not to switch to a drug with a better
side effect prole. In this approach,the consideration whether or not to disclose the information
1.
Fully informed consent: patients are given all information required for them to freely mak
decisions where they understand and appreciate the consequences of taking a par
medication, of participating in a research study, or allowing their health information to
shared
2.
Integrated consent: usually used in the context of pragmatic trials where the
consent process is integrated with the research consent process
3.
PUBLIC TRUST
PATIENT AUTONOMY &
Fig. 14.2 The continuum of approaches to informed consent in data-generating activities
Contextualized consent: clinicians make decisions based on their knowledge of the patient
and the patient’s condition about how much information to provide to maximize
autonomy whilst simultaneously minimizing the risk of harms from disclosing pote
nocebogenic information
4.
Consent waiver: in some circumstances and jurisdictions, the need to obtain consent
waived when consent can negatively impact data validity and quality, creat
problems, and/or distress participants
324
A. Thompson and A. Komparic
on side effects in both nonspecic and drug-specic side effectswill be inuenced by the nature,
severity and seriousnessof possible side effects,
its likely impact on medication adherence and the
patient’s daily life.This model of contextualized
informed consent requires healthcare practitioners to take into consideration who the patient is,
what they are treating, and how their relationship
with the patient plays a role in how patients take
up information about side effects to maximize
patient autonomy without causing harm in the
process.
Recent methodological developments in drug
comparative effectiveness research, such as cluster randomized trials of prescribing policy, pragmatic trials, or when data are anonymized, are
generally considered to be low risk to patients,
but questions about whether individual informed
consent from patients is necessary have been
raised [14, 15]. Because seeking individual consent from each patient/participant contributes to
the costs of such studies, as well as potentially
negatively impacting study enrollment, some
have proposed an opt-out, rather than opt-in
approach to enrollment for studies that are low
risk and where there is genuine clinical equipoise
or where community consent is more appropriate
[14, 16]. However, whether or not this is permissible will depend on the jurisdiction where the
research is being conducted and whether or not
the jurisdiction has something comparable to the
Common Rule in the United States that articulates the situations in which consent can be
exempt from ethical review [17]. A proposal for
“integrated consent” for pragmatic trials that
integrates the clinical consent process with the
research consent process avoids the ethically
problematic proposal to not seek consent at all
for pragmatic trials [18], which would involve
deceiving patients. International research ethics
guidelines vary on this, and the Good Clinical
Practice guidelines that govern clinical trials do
not allow for waivers of informed consent [19].
Ultimately, the clinician has a duciary duty to
the patient to act in a trustworthy manner, and
failure to disclose research participation to
patients may well damage the therapeutic alliance between provider and patient. This is unlike
reporting of adverse events in most jurisdictions,
which is not considered a violation of patient
condentiality, such as in the UK’s Yellow Card
system, and therefore does not require patient
consent to report. In the context of research, there
is, of course, mandatory reporting of adverse
events which also does not require explicit consent from research participants.
Pharmaceutical companies continue to evolve
into information gathering companies through
their ownership of online medical practices that
systematically collect patient data and through
data mining activities [20, 21]. Patients use applications on their smartphones and other devices to
monitor and collect their own health data that is
then mined often without their informed consent
because of the impenetrability of the legalese in
app agreements or because there is no express privacy or tracking agreement [22–24]. Where pharmacovigilance activities use these data, or where
healthcare professionals use mobile applications
to store or collect patient data, care must be taken
to ensure data were collected ethically, and in
keeping with relevant privacy and consent laws.
5 Disclosure
In addition to duties to disclose information to
patients to facilitate their ability to make informed
decisions, healthcare practitioners often have formal disclosure responsibilities when medication
errors or violations occur. Harms from medications are sometimes the result of human error, system error, or even negligence and recklessness
such as deliberate off-label use or administration.
Violations can also occur when behavior leads to
neglect of safety monitoring, which can be motivated by cost-cutting or disregard for monitoring
or reporting requirements. The importance of disclosing medication errors and violations for patient
safety has been widely recognized as an essential
part of preventing future errors, maintaining the
trust of patients and the public, and is also essential for repairing therapeutic relationships and
patient/family healing [25]. It is typically a formal
process of communication between a clinician
and/or organization and the patient or their family
members. Ethically, a clinician has a duty to warn
in particular situations, and disclosure of medical
14 Ethics inPharmacovigilance
325
error is at least partly about warning others about
potential systemic or root causes of medication
errors so that they can be prevented in the future. If
an institution does not have a culture of error
reporting that is nonpunitive, it will discourage the
transparent disclosure of medication errors, which
in turn has a negative impact on patient safety [26,
27]. In the case of deliberate violations or reckless
disregard for protocols, sanctions may well be
appropriate in addition to disclosure.
In addition to having a duty to warn others of
potential drug safety issues related to error and
deliberate violations, healthcare practitioners
have a duciary responsibility to patients that is
rooted in their obligation to act in the best interests of the patient. When medication errors or
violations occur, healthcare practitioners are
accountable to patients for their actions and the
need for healthcare practitioners to be honest
with patients and not withhold the truth about an
error, or even a near-miss incident, requires disclosure. While most errors are related to decisionmaking mistakes, institutional factors can also
contribute to errors [27] and also possibly deliberate violations if cost-cutting and lack of time
are issues. Disclosure to colleagues and others in
institutions where there are institutional or systemic causes of error would also be important for
creating a culture of safe medication use.
Globally, there are disparities between highincome countries and low-income countries with
respect to the prevalence and quality of pharmacovigilance: patients living in low-income countries
experience twice as many disability-adjusted life
years lost due to medication-related harm than
those in high-income countries [28], and this is
partly attributable to lack of global cooperation
around pharmacovigilance [29]. Given that most
medication errors are avoidable, this presents an
opportunity for high-income countries to share
data and resources for error reporting and medication safety incidents with low-income countries,
who may lack the resources and systems to monitor
and redress adverse events and errors. Despite the
comparative lack of infrastructure and/or resources,
innovative uses of disease monitoring systems for
reporting adverse events and South-South collaboration are promising to improve pharmacovigilance
systems and capacity in the Global South [30].
6 Equity
Healthcare practitioners can also help protect
their patients and the public by being vigilant
about how inequities in clinical trial design
might impact real-world safety and effectiveness of drugs and vaccines (Fig. 14.3). This
might require that study populations in clinical
trials be examined to identify the potential need
for targeted monitoring in the post-market context because a lack of diversity in clinical trials
can make existing health inequalities worse or
create new inequalities [31]. There are gaps in
our knowledge that result from the failure to
recruit diverse populations for inclusion in clinical trials, and this can result in clinical blind
spots about how drugs, devices, and behavioral
interventions affect different groups of people—and often they are the people most affected
by a particular disease or condition [32]. A
recent review of studies reporting on randomized clinical trials revealed that little progress
has been made in increasing the reporting and
representation of participants’ racial and socioeconomic status, despite the fact that reporting
of their sex has increased [33]. Healthcare practitioners involved in clinical trials are being
urged to collect and report data “in ways that
allow them to be aggregated in systematic
reviews of the literature” [34].
Equity issues are not limited to representation and reporting issues in clinical trials, however. Given the challenges of running trials that
are diverse and large enough to generate statistically valid observations about sub-populations,
partnering with people from poorly and underserved groups in society so that their unique
perspectives can be brought to bear on study
design is equally important [34]. Partnership in
study design is relatively new to clinical trial
research but is increasingly recognized to be
important from an ethical perspective, especially in the context of global health research
where it is important to account for diverse
experiences and perspectives concerning
research practices as well as accessing and using
pharmaceuticals [35, 36].
As pharmacovigilance goes digital and relies
increasingly on big data and algorithms to iden-
326
Equity Considerations
A. Thompson and A. Komparic
EQUITY
Data absenteeism redressed through concerted efforts to
improve reporting of adverse events and sequencing of
diverse genomes. Data ownership proactively addressed
Inclusive study design that allows participants to
partner in the research design and process
Broad representation of clinical trial participants and
identification of populations who may need targeted
post-market surveillance to redress the lack of diversity
Fig. 14.3 Contributing factors to equitable or inequitable clinical trial design
in clinical trials
tify safety and effectiveness issues, the gaps in
knowledge of how drugs impact underrepresented and/or marginalized populations are replicated as issues of “data absenteeism” in
pharmacovigilance databases (where certain populations may be entirely absent), as well as in
pharmacogenomic databases [37, 38]. In the context of disparities in access to digital reporting
technologies, patient reporting of adverse drug
reactions (ADRs) can be difcult, and this can
create gaps in reporting. As these databases are
mined for information about safety, effectiveness, and idiosyncratic drug reactions related to
genetic makeup, it is important to ensure that
data absenteeism is recognized and actively
addressed to prevent or at least not exacerbate
health inequities. Such inequities can be reected
as missing information in the risk management
plan a pharmaceutical company must produce for
Pharmacovigilance and pharmacogenomic databases
reflect data absenteeism from reporting difficulties in
digital systems where entire groups are not captured
Research focus is narrowed to concerns irrelevant to
communities, is not responsive to participant concerns,
and benefits and burdens of research are not
Clinical blind spots resulting from lack of diversity in
clinical trials, and post-market studies or from lack of
reafrming socially constructed categories of
race which do not match the biological reality
that intrapopulation genetic variation can be
greater than inter-population variation. Decisionmaking in pharmacogenomic practice may overrely on racial categories that are uid and socially
constructed and mistakenly use categories such
as White or Asian as surrogates for actual data
about genetic variation that can be generated
through universal testing [39]. The need for
diversity in pharmacogenomic data is compelling
and needs to be done thoughtfully in order to
avoid worsening existing health disparities by
excluding marginalized populations, while not
overgeneralizing based on misguided notions of
race [40]. Issues of consent for data collection,
data ownership, and usage (particularly in
Indigenous communities) need to be ethically
addressed prior to expanding databases.
new medicines.
Pharmacogenetics also raises concerns about
how populations are screened for genetic predis-
7 Trust
positions to adverse drug effects. The creation of
categories of risk in the population based on
stratication of such things as race or multigenerational ancestry has become accepted in clinical practice, but such an approach risks
Recruitment of diverse populations for research
and inclusion in databases that can be used in
pharmacovigilance activities can be a challenge
because of historical issues of mistrust in science,
INEQUITY
distributed fairly
appropriate reporting of data
14 Ethics inPharmacovigilance
327
scientists, healthcare practitioners, or other
authorities by people who have been subject to
systemic racism, sexism, or other forms of discrimination by society or within the healthcare
system in particular [32]. This mistrust can spill
over into the clinical encounter, as systemic
forms of discrimination are also present in the
clinic. In the context of prescribing, being transparent about what is known about a drug and its
side effects, as well as what is not known can go
some way to helping healthcare practitioners
build trust with their patients. As discussed above
in the section about the importance of disclosure,
the need to be truthful with patients can sometimes conict with the desire to be able to conduct health systems level research. However,
since patient trust is so central to the clinical and
therapeutic relationship and is enshrined in the
clinician’s duciary duty, the impact of clinical
decisions on patient trust should be top of mind.
Not only can trust in the clinician be undermined
when important information about side effects or
patient involvement in data collection is not disclosed or is not accessible to the patient, public
trust in a health profession as a whole can be
undermined. As discussed further below, healthcare practitioners ought to also be aware of how
actual or perceived conicts of interest can
impact patient and public trust in the safety of
pharmaceuticals and the integrity of prescribers
and researchers. In systems with publicly funded
pharmaceutical insurance, access to medicines
can be limited to those that meet pharmacoeconomic criteria (e.g., cost-effectiveness) for reimbursement. In some cases, this can result in
patients receiving less effective medications, or
not being able to access medicines available to
those who can pay out of pocket. These situations
can be perceived by some as limiting choice,
which may also potentially impact public trust.
Public trust in health professionals and in science
itself is crucial for effective health systems and
for research participant recruitment for drug trials and even adverse event reporting [41].
Pharmacovigilance can help bolster public trust,
but it also relies on the willing participation of a
trusting public.
8 Inclusiveness
As a counterpoint to the equity issues created by
a lack of inclusiveness or representation of
diverse patient populations in clinical trials,
patient engagement in pharmacovigilance activities is growing. As “citizen science” has become
increasingly valued in many areas of science,
there has been increasing engagement of patients
and the broader public in pharmacovigilance and
pharmacoepidemiology and there are now guidelines on engaging patients in research across the
drug life cycle [42]. Drug safety monitoring systems are being designed to receive patient- reported
outcomes, and internet-based surveys about
adverse events can be administered to patients
directly with relative ease, and countries engaging patients this way see these data to be of scientic value [43]. Not only does this illustrate an
improvement in how adverse event data can be
collected, but it also indicates a change in how
pharmacovigilance researchers, clinical trialists,
and healthcare practitioners value the patient perspective [44].
As sociologist Nicky Britton has observed,
there are several reasons why this is signicant.
The rst is that respect for persons involves taking patients seriously, otherwise “interactions
with professionals can be profoundly damaging”
[45]. Patients are not empty vessels to be lled
with information from their healthcare practitioners: how patients respond to the advice of their
healthcare practitioners is crucial to the effectiveness of treatment, but they will have their own
“ideas, experiences, concerns and so on…” [45].
And lastly, engaging with publics during the
research process “can help to ensure that academics attend to issues of importance to patients,
which may also affect the delivery of health care”
[45]. Respect for persons, which is the underlying ethical principle in patient autonomy, requires
healthcare practitioners to attend to their patients’
stories, especially when something their physician has prescribed (recently or in the past) might
have harmed them in some way. Expanding
notions of harm to include patient perspectives
on, and the social context around, how drugs
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