Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5389_Библиотеки_им_академика_М_И_Перельмана
.pdf
18
J. Jose et al.
Following the detection of a drug signal,
post- marketing studies can be undertaken for
signal testing. They can take the form of observational studies, such as cohort studies or case–
control studies depending on the nature of the
event being examined. Such studies may be able
to prove associations, although causality may
still be difcult to ascertain. Increasingly, there
is use of big data for data mining in novel realworld datasets from health-care systems [71].
Chapter 6 elaborates on pharmacoepidemiology
and the use of real-world data. Further on, Chap.
16 outlines the various study designs of post-
authorization safety studies (PASSs) used to
identify ADRs and summarizes the various
strategies to predict and thereby prevent ADRs
such as pharmacogenetics, use of omics, and in
silico approaches, including articial intelligence. Increasingly, the electronic health-care
database studies that are used for hypothesis
testing are also being explored for near realtime monitoring and rapid response analyses
[72, 73]. Such databases can be used for hypothesis generation, i.e. signal detection, although
for the latter there is little compelling evidence
to date that signals can be consistently identied
earlier through spontaneous reporting [74].
inspected by regulatory authorities to assess
how well companies are meeting pharmacovigilance requirements.
Pharmacovigilance has become increasingly
intricate and multifaceted, looking at all the
safety elements of a drug from the inherent properties of a molecule to the licensed and unlicensed uses of the drug in clinical practice. This
requires multiple types of expertise, including
experts in risk management and risk minimization, epidemiologists, statisticians, and clinical
experts with disease and therapeutic knowledge.
Scanning for safety outcomes from unlicensed
usage and medical errors as well as manufacturing issues are also part of modern pharmacovigilance, as is implementing and measuring the
effectiveness of risk mitigation strategies. The
principles and practice of pharmacovigilance in
the industry are discussed in the rst part of this
book from Chaps. 6 to 14. For more details on
pharmacovigilance in the industry, see Gatto
etal. [75], Talbot and Nilsson [76], and Hartford
etal. [77].
12 Communications
inPharmacovigilance
11 Pharmacovigilance
intheIndustry
The pharmaceutical industry has ensured that it
has processes in place to monitor the benet–
harm ratio of its products under development
and also after it has been marketed. As safety
issues arise, action is taken as needed. In addition to conducting pharmacovigilance activities across the life cycle of a drug, companies
must also ensure that they have set up
approaches, including safety governance. To
achieve these objectives, quality processes
need to be clear and t for purpose. These processes should be open to and be frequently
Detecting new ADRs and the subsequent regulatory decisions, short of withdrawing a drug
from the market, may have limited impact without good communication. There are two main
areas where particular complexity exists. First,
the communication of benets and harms to
stakeholders, including patients and the public
and, second, inuencing the prescribing and
monitoring of medicines by health-care
professionals.
Communicating theriskof harms to patients
and the public is hard, even when the facts are
clear. However, pharmacovigilance is a complex
science, using multiple sources of data. There is
a large amount of uncertainty inherent in the
eld. This makes communication critical and
1 Introduction toDrug Safety andPharmacovigilance
19
challenging when communicating risks of
harms and benets clearly to health-care professionals and patients. Much effort in recent years
has considered approaches for effective communication to stakeholders and enabling informed
decision- making [78]. Openness and clarity on
uncertainties is important in communication.
Yet, the open availability of pharmacovigilance
data carries dangers, since it can be taken out of
context and misused either unknowingly by
those who misunderstand the nature of the data
sources or by bad actors. This has been demonstrated by often deliberate attempts by bad
actors to use data from the US VAERS system to
create narratives around the coronavirus disease
of 2019 (COVID-19) vaccines, and such data
have been misused in the past around previous
vaccine scares. Chapter 11 provides a broad
overview of this component from various perspectives. It is important for practitioners, regulators, and other stakeholders to be aware of
information sources for drug safety and communicating risks in clinical practice, which is discussed in Chap. 17.
The use of a clear risk management plan based
on best practice and inuencing prescribers to
change practice can be difcult [79], and there
are many examples of the failure of warnings to
change prescribing practice [80]. However, there
are examples of how sustained efforts can lead to
signicant improvements in prescribing.
Following the voluntary withdrawal of rofecoxib
in 2004, the UK’s MHRA issued guidance in
2005 on the increased thrombotic risk associated
with other NSAIDs and the relative safety of
some NSAIDs (naproxen, ibuprofen) compared
to others (diclofenac). The UK’s National
Prescribing Centre carried out a series of interventions, including therapeutic bulletins,
e- learning materials, and therapeutic workshops,
which was associated with a signicant fall in
diclofenac prescribing and a proportionate
increase in the use of naproxen and ibuprofen
[81]. Changing ingrained practices and clinical
decision-making requires long-term multidisciplinary efforts.
13 A Multidisciplinary
Approach
toPharmacovigilance
A multidisciplinary approach is essential to
address drug safety challenges. Pharmacovigilance
is a challenge that is increasingly taken up by
multilateral organizations and institutions,
including hospitals, academia, community pharmacies, pharmaceutical companies, medicine
regulatory authorities, and other independent
institutions [27]. Along with health-care professionals, patients increasingly play a noteworthy
role in pharmacovigilance. At the same time,
patient organizations progressively position
themselves as stakeholders in pharmacovigilance, carrying out many activities that stimulate
awareness and participation of the public in drug
safety [82]. Pharmacovigilance systems face a
common set of ongoing challenges in drug safety
surveillance in ve principal interrelated areas:
engaging the public, collaboration and partnerships, incorporating informatics, adopting a
global approach, and assessing the impact of
efforts. Accordingly, to tackle the multifaceted
challenges of pharmacovigilance, a sciencebased, public health-focused, collaborative, and
global approach is needed. Active engagement
of patients and practitioners in pharmacovigilance, collaboration of pharmacovigilance centres with other public health agencies, appropriate
utilization of informatic systems, and assessment of the impact of various strategies on
improving health outcomes are all crucial [83].
The importance of multidisciplinary approach in
pharmacovigilance and contribution of various
stakeholders is discussed in Chap. 13. The
involvement of patients, specically in the entire
process of pharmacovigilance and drug safety, is
discussed in Chap. 12.
20
J. Jose et al.
13.1 Pharmacovigilance Education
The burden of known AEs from medicines and
the importance of detecting new signals of
potential harms mean that education on the
importance of pharmacovigilance is essential
for health-care practitioners to play their part.
The underreporting of suspected ADRs to regulators has led to various attempts to improve the
reporting of adverse reactions. Limited pharmacovigilance knowledge demonstrated by healthcare professionals is one among the main
reasons for the underreporting of ADRs [84]. In
practice settings with multiple medications,
complex regimens, and better health-literate
patients, there is an additional demand for
health-care professionals to have up-to-date
knowledge on drug safety [85].
Concern about the state of pharmacovigilance
knowledge within professions [86] has led to the
development of model curricula to inform educators [87] as well as to the incorporation of
pharmacovigilance into the educational standards of professional regulatory bodies. More
recently, it appears that there has been a greater
uptake of pharmacovigilance in undergraduate
programs worldwide [88]. There have also been
interesting experiments such as including undergraduates directly in pharmacovigilance by evaluating spontaneous ADR reports and writing
feedback letters with regulatory oversight and
imparting medication safety education through
games [89, 90].
At the postgraduate level, various attempts to
insert the key concepts of pharmacovigilance into
education have been made, including by continuing professional development, by providing
online education about pharmacovigilance (as
done by many drug regulatory agencies), and by
engaging with professional regulatory bodies to
ensure that the commitment to improve medicine
safety is highlighted. Additionally, the WHO
UMC provides news updates on the current issues
in pharmacovigilance via publications, podcasts,
and training. The International Society of
Pharmacovigilance (ISoP) holds various meet-
ings centred on training and education, including
a major conference with pre-conference educational sessions.
For those whose primary role is pharmacovigilance, either working in regulation or in the
pharmaceutical industry, there are specialist
qualications in pharmacovigilance. There is a
growing need for pharmacovigilance capacity
building among various stakeholders, including
health-care professionals, industry, local health
workers, regulators, policy makers, health carerelated nongovernmental organizations, researchers in health-care disciplines, and teachers at
universities and hospitals. The WHOInternational Society of Pharmacovigilance
(ISoP) Core Elements of a Comprehensive
Modular Curriculum is a broad pharmacovigilance curriculum, which lists the essential elements of pharmacovigilance education and
training [85].
In general, education of health-care professionals should also focus on awareness, on considering
ADRs as part of the differential diagnosis, and
knowledge on having a sound understanding of the
most frequently used drugs and their ADRs, on the
predisposing factors for ADRs, on the causes of
medication errors, and on the reporting of ADRs
and medication errors. Clinical appraisal skills and
pharmacovigilance competencies in clinical practice should be inculcated as part of training, which
must include prevention, identication, analysis,
management, and patient communication related
to drug safety issues. Both current and future
health-care professionals should be aware of the
need for and the outcome of pharmacovigilance
and reporting of ADRs and the process of ADR
reporting [87, 91–93].
Patients should also be encouraged to take an
active step in promoting drug safety by educating
them on the safe use of medications, monitoring,
and reporting drug safety issues. Many countries
allow and encourage patients to report ADRs,
and such reports can be complementary to those
reported by health-care professionals. To achieve
patient reporting, it is of importance to create
awareness among the public on the need to report
1 Introduction toDrug Safety andPharmacovigilance
21
ADRs and how to report them. The reporting system should be patient- and carer-friendly [94].
14 Drug Safety in Clinical
Practice
In clinical practice, the concern shifts to the individual care of patients and the associated clinical
decision-making, rather than the population-level
concerns about drug safety. Although there is
variation in the prevalence of preventable ADRs,
it is clear that there are ways in which the exposure to potential harms from medicines can be
reduced. These can be summarized as follows:
1. Careful initiation of medicines
2. Timely and regular review of medicine use
3. The use of additional technologies such as
pharmacogeneticsand decision support tools
in 1 and 2
At least 1in 20 admissions to a hospital are
associated with the harmful effects of medicines
[95]. The increasing issue of harmful polypharmacy, linked to increasing comorbidities, is a call
to action. There is now a global movement,
termed ‘deprescribing’, to remove inappropriate
medicines. Deprescribing has been dened as
‘the process of withdrawal of an inappropriate
medication, supervised by a health-care professional with the goal of managing polypharmacy
and improving outcomes’ [96].
The causes of polypharmacy are many and
pharmaceutical marketing, multiple disease state,
evidence-based medicine guidelines, government
targets, and sociocultural expectations of treatment are just some of them. However, there is
some optimism that despite the demographic
changes that will lead to an increasing potential
of inappropriate prescribing, changes in healthcare systems, such as the extension of clinical
pharmacists into primary care, increasing prescribing rights, and the development of pharmacogenetics, may attenuate the risks. There are
also several screening tools (such as theScreening
Tool of Older People’s Prescriptions [STOPP]/
Screening Tool to Alert to Right Treatment
[START] criteria), which may help. Chapter18
describes several screening tools and provides an
extended discussion of polypharmacy and deprescribing. With the increasing prevalence of polypharmacy, the signicance of considering drug
interactions in clinical practice has increased.
Chapter 4 discusses the mechanisms by which
drug interactions occur and outlines how drug
interactions can be managed and prevented in
practice.
Elements of pharmacovigilance training are
directly useful at the individual patient level, as
much as they are in the regulatory environment,
or for encouraging the reporting of ADRs. For
example, an understanding of the principles of
causality assessment is useful for clinical
decision- making when an ADR is suspected in a
patient (Chap. 8), as are the issues around patient
susceptibilities and prescribing in selected
groups: children, elderly, pregnant and breastfeeding mothers, and patients with renal and
hepatic dysfunction (see Chaps. 19 to 22).
An increasing number of drugs now have
pharmacogenetic guidance. A recent cluster randomized, cross-over implementation of a 12-gene
panel, covering 6944 patients in 7 European
countries, has found that the incidence of clinically relevant ADRs was signicantly reduced
(21.0% with screening versus 27.7% without)
[97]. The implementation of screening more
widely could thus have benecial effects in clinical practice. Pharmacogenetics is further discussed in Chap.23.
Reducing medication errors has been a point
of focus in recent years, with the WHO’s third
Global Patient Safety Challenge attempting to
reduce the global burden of iatrogenic medication-related harm by 50% [98]. In the case of prescribing errors, the UK’s EQUIP study found a
rate of 8.9 errors per 100 medication orders
(11,077 errors were detected in 124,260 medication orders). Other studies have shown that as
many as a quarter of all prescribing errors could
have been prevented using electronic prescribing
systems [99]. Such reductions can be achieved
through the removal of legibility issues and com-
22
J. Jose et al.
puter-aided prescribing decisions. There is strong
evidence that the use of electronic prescribing
reduces the number of prescribing errors [100],
although they have also led to novel forms of
errors and, in some cases, more severe errors
[101]. Poorly designed electronic prescribing
systems can also be associated with new forms of
errors, such as drop-down menus leading to picking errors, causing incorrect dosing. Overall, the
effect of electronic prescribing will lead to
improved patient safety, but it is important that
users are actively engaged and trained. A detailed
discussion of medication errors, including the
components of medication errors, its detection,
and mitigation strategies, can be found in
Chap.15.
15 Pharmacoinformatics
andArticial Intelligence
inPharmacovigilance
15.1 Pharmacoinformatics
andPharmacovigilance
The inuences of information technology in
drug-related areas have resulted in the application of a specic branch of medical informatics
known as pharmacoinformatics [102]. The specialty of ‘pharmacoinformatics’ combines bioand chemoinformatic approaches as well as
articial intelligence (AI) to support drug design
and development at various stages, starting from
preclinical research support to clinical trial
design and execution support, as well as pharmacovigilance, pharmacoeconomics, and personalized medicine [103]. Pharmacoinformatics has
an important role to play in the success of pharmacovigilance at the hospital, industry, and regulatory levels. It will facilitate reporting of ADRs,
and, in addition, it will revolutionize signal detection using data mining techniques. At the clinical
level, as more health-care settings implement
computerized physician order entry along with
advanced decision support systems, this can
greatly inuence the prevention of medication
errors [102].
15.2 Articial Intelligence
andPharmacovigilance
There are signicant opportunities and challenges in utilizing advanced information technology within pharmacovigilance systems and
across the pharmaceutical industry [104]. There
is great interest in the application of AI to pharmacovigilance [105]. AI is a broad eld, including replicating human cognition by machines and
computers [106]. Machine learning (ML) is a
subset of AI that automatically enables a machine
or system to learn and improve from experience
[107]. Pharmacovigilance’s broad scope, with the
need for processing extensive data to achieve
regulatory, scientic, and clinical objectives, plus
a growing treasure of data and technology, makes
it a high-grade ore for mining by AI [106].
Pharmacovigilance requires ongoing surveillance of the known side effects of medicines as
well as sifting through large volumes of data to
identify and act on emerging, previously unknown
side effects [108]. AI could tackle large, complex, high-dimensional data containing complex
nonlinear relationships [106].
Various aspects of pharmacovigilance will
benet from automation, subject to good pharmacovigilance standards of practice. These
include individual case safety report (ICSR) processing, signal management, pharmacovigilance
quality management systems, and risk management systems [104]. ICSRs will very likely
remain an important part of pharmacovigilance
for the foreseeable future. The continually growing number of ICSRs from an increasing number
and variety of data sources that are processed,
submitted, and assessed for safety signals leads
to increased costs and workloads for a limited
supply of human safety experts [105]. The overall goal of automation is to provide high-quality
safety data in the correct format, in context,
1 Introduction toDrug Safety andPharmacovigilance
23
more quickly, and with less manual effort, and
AI potentially plays an important role in improving the efciency and scientic value of ICSRs
[104, 105].
In a recent paper that has analysed the studies
related to use of AI in the pharmacovigilance
industry, the major trends and opportunities
included data ingestion, disease-specic studies,
literature reviews (i.e. for signal detection), leveraging real-world data, signal detection in spontaneous safety reports, and the use of social media
data [109]. The current areas of AI activities in
assessment, proof of concept, or development for
production include digital media screening,
extracting data from source documents, checking
for duplicate reports, case validation, triage, and
initial assessment of cases and data entry, medical assessment, including causality, narrative
writing, and coding AE concepts [110, 111].
Furthermore, AI has been used to search for leads
in vast amounts of social media data for real-time
signal detection but with several associated limitations [106]. To date, such approaches have had
a limited practical impact.
According to a recent systematic review
assessing the role of AI in pharmacovigilance
and drug safety, it has been reported that the
most identied uses include identication and
prediction of ADRs, followed by the processing
of safety reports or clinical narratives and extraction or prediction of the effects of drug–drug
interactions [112]. Application of AI technology
in clinical practice could assist in safer use of
medications in practice by its potential to
improve disease diagnosis, treatment selection,
clinical laboratory testing, and minimize human
errors [113]. AI could be used to identify populations at high risk of experiencing ADRs, to predict ADRs, to identify potential drug interactions,
to optimize medication dosages, to guide personalized medicine, and to improve patient education using innovative and effective ways [112,
113]. AI could also be utilized in drug informa-
tion and consultation, thereby promoting drug
safety by designing a new support system to
assist practical decision-making tools for healthcare providers [113].
Table 1.6 Potential applications of articial intelligence
in promoting drug safety and facilitating pharmacovigilance activities
Industry and regulatory agencies
Monitoring large volumes of complex, highdimensional data to identify and act on emerging,
previously unknown side effects
Individual case safety report (ICSR) processing,
including data ingestion, case validation, triage, and
initial assessment of cases, medical assessment,
including causality, narrative writing, and coding AE
concepts
Signal detection and management from spontaneous
reports, literature reviews, digital media screening
Pharmacovigilance quality management systems
Risk management systems
Leveraging real-world data
Identifying clusters and patterns in data that might
not be possible with rules-based systems.
Clinical/health-care settings
Improving disease diagnosis and clinical laboratory
testing
Assisting in treatment selection and medication use
using practical decision-making tools for health-care
providers
Optimizing medication dosages and guiding
personalized medicine
Improving patient education
Identifying populations at high risk of experiencing
ADRs and potential drug interactions
Minimizing human errors related to medications
[104–106, 108–112].
The potential applications of AI in promoting
drug safety and facilitating pharmacovigilance
activities from the perspective of the industry,
regulatory agencies, and health-care settings are
summarized in Table1.6.
15.2.1 Challenges inUsing Articial
Intelligence
inPharmacovigilance
There are multiple challenges or limitations associated with the use of AI in real practice. AI
should be implemented in pharmacovigilance
only when it can help provide solutions that
reduce the workload, complexity, or budget associated with pharmacovigilance or, otherwise, it
could potentially make the pharmacovigilance
system inconsistent and decrease public trust and
patient safety [108]. It is not always possible for
machines to match the accuracy/compliance of
24
J. Jose et al.
pharmacovigilance professionals, especially in a
highly regulated area, thus underscoring the need
to precisely dene operational objectives of using
AI in pharmacovigilance [106]. The performance
of the current AI algorithms for ICSR processing
and evaluation requires a ‘human in the loop’ to
ensure good quality [104]. As there are concerns
about the clarity and ease of interpretation of outputs, we must ensure that humans are in the loop
so that they are able to make appropriate decisions based on the AI output, given that AI outputs are not perfect. The need for human expertise
must be addressed for the ethical and effective
implementation of AI in health care [113].
Considering that the data obtained through pharmacovigilance activities are likely to be heterogeneous, data are captured and shared imperfectly,
analytics through AI could be challenging, especially to determine the validity of the data [108].
Challenges related to data privacy, misuse of
data, bias, and dangers of sharing data might
deter from free sharing of data for analysis by AI
tools, which can decrease the performance of
such analysis and hinder the real implications
[108, 113]. The quality of AI and ML studies will
improve over time, providing more robust studies
with better generalizability. The challenge of
converting ML research studies into production
AI for effective trusted routine use has not yet
been resolved, except for highly limited specic
pieces of the pharmacovigilance life cycle (such
as surveillance of the published literature for
identication of reportable safety events).
Although we expect progress in this area, it is
unclear how rapidly advances will occur.
15.2.2 Future ofUsing Articial
Intelligence
inPharmacovigilance
Technology does hold increasing potential for
automating pharmacovigilance functions.
Although progress has been uneven, there have
been successes so that barriers to development
and implementation can be reduced or resolved,
making the routine use of AI to perform pharmacovigilance functions more likely [109]. Several
measures must be taken to ensure responsible and
effective implementation of AI in health care,
including developing and implementing comprehensive cybersecurity strategies to protect patient
data and critical health-care operations [113].
Collaboration between industry personnel,
health-care organizations, AI researchers, and
regulatory bodies is crucial to establish guidelines and standards for the development and
trusted deployment of AI algorithms as part of
routine pharmacovigilance [108, 113].
16 Ethics inPharmacovigilance
Ensuring that patient data are securely managed
and that understanding of the benets and harms
of medicines is communicated to them appropriately and in a timely manner for informed
decision- making is central to pharmacovigilance.
As discussed, pharmacovigilance deals with considerable uncertainty.
Ethics in pharmacovigilance can be complex.
The risks of harms should be identied and fully
understood as quickly as possible and constantly
evaluated against expected and actual benets.
The decision to remove a medicine from the market is not a neutral act since it removes the benets of a drug from patients.
It has been argued that the precautionary principle should be applied within the context of drug
safety, particularly when it comes to vulnerable
patient groups such as the elderly and the children [114]. It has also been suggested that if there
is any risk of a safety issue, then therapeutic
intervention should be avoided and, in some
cases, even to the extreme of product withdrawal
from the market worldwide.
However, since potential safety signals arise
quite often, and many may ultimately be
refuted, the precautionary principle may be an
ill t when the benets are high. Misapplication
of the precautionary principle could lead to
erratic decision- making, leading to a net
increase in harm caused by market withdrawal
of a drug providing a net benet. An example
might be the European pause in the use of the
AstraZeneca COVID-19 vaccine in older
patients following the discovery of a rare clotting disorder, when there were limited alter-
1 Introduction toDrug Safety andPharmacovigilance
25
nate vaccines, and a high prevalence of
COVID-19 infections. Clearly, caution should
be exercised when applying the precautionary
principle in pharmacovigilance.
However, what is clear is that there should be
open and continued discussion on the expected
benets and likely harms at both the general and
individual patient levels. The possibility of drug
causation of an AE should not be dismissed when
dealing with limited evidence [115]. A full discussion of ethics in pharmacovigilance can be found
in Chap. 14.
17 Future Challenges
Identifying and analysing suspected ADRs are
likely to remain the bedrock of pharmacovigilance for the foreseeable future—recent reviews
have continued to show the dominance of spontaneous reporting as a source of signals. As we
move to more of a ‘big data’ world [116], connecting, enriching, and contextualizing AEs with
other data streams, leveraging emerging technologies like large language models [117], and
other new AI developments will all remain critical. However, understanding the concerns of
patients and health-care professionals [118]
about the adverse effects of medicinal products,
and communicating useful information to ensure
appropriate benet–harm proles of medicines,
and prevent and mitigate harms in individual
patients must remain at the heart of all that we
do.
Many of the pharmacovigilance practices
have evolved over time with drivers such as legislative requirements. Differences, internationally,
have led to complex processes and activities with
sometimes limited evidence, if any, for a signicant positive impact on patient safety, e.g. submission and exchange of ICSRs to multiple
recipients. There is much activity in pharmacovigilance, which is critical, however, and we
must as a eld strive to ever better focus on those
activities that will most positively impact patient
safety. Better patient engagement and personalized safety are key future directions.
18 Summary and Conclusions
As medicines are one of the key interventions in
health care, ensuring that a positive balance of
benets and harms exists for medicines at the
population level is essential. The science of pharmacovigilance is constantly evolving with the
incorporation of new methodologies, data sources,
and technologies such as pharmacogenomics and
AI. However, the clinical suspicions of healthcare professionals will remain important for the
detection of ADRs, and, increasingly, there will
be more involvement of patients in individual
decision-making as well as in regulatory settings.
At the individual level, the burden of ADRs can be
reduced by ensuring the rational evidence-based
use of drugs and by performing regular reviews of
prescribed medicines. A key component of pharmacovigilance is communication, which can be
complex, particularly in evolving situations—
both at the individual level and when addressing
the wider public.
Disclosure Statement Andrew Bate is an employee of
GSK and holds stock and stock options.
References
1. Rawlins MD. Pharmacovigilance: paradise lost,
regained or postponed? The William Withering
Lecture 1994. J R Coll Physicians Lond.
1995;29(1):41–9.
2. Mann R, Andrew E. The Basis of pharmacovigilance: introduction. In: Mann R, Andrews E, editors.
Pharmacovigilance. 2nd ed. Chichester: John Wiley
and Sons Ltd; 2007. p.3–11.
3. World Health Organization. Regulation and prequalication. 2023. Available at: https://www.who.int/
teams/regulationprequalification/regulation-andsafety/pharmacovigilance. Accessed 9 Nov 2023.
4. Council for International Organisations of Medical
Sciences. WHO Working Group on Vaccine
Pharmacovigilance. Denition and application of
terms for vaccine pharmacovigilance. 2012. https://
cioms.ch/wp- content/uploads/2017/01/report_working_group_on_vaccine_LR.pdf. Accessed 1 Dec
2023.
5. Fornasier G, Francescon S, Leone R, Baldo P. An
historical overview over Pharmacovigilance. Int J
Clin Pharm. 2018;40:744–7.
26
J. Jose et al.
6. Routledge P. 150 years of pharmacovigilance.
Lancet (London, England). 1998;351(9110):1200–
1. https://doi.org/10.1016/S0140- 6736(98)03148.
7. Stephens MD.The dawn of drug safety. Hampshire:
George Mann; 2010.
8. Van Grootheest K. The dawn of pharmacovigilance: an historical perspective. Int J Pharm Med.
2003;17(5–6):195–200.
9. Geiling EMK, Cannon PR. Pathogenic effects of
elixir of sulfanilamide (diethylene glycol) poisoning. JAMA. 1938;111:919.
10. World Health Organization. WHO urges action to
protect children from contaminated medicines. 23
Jan 2023b. Available at: https://www.who.int/news/
item/23- 01- 2023- who- urges- action- to- protectchildren- from- contaminated- medicines. Accessed
13 Nov 2023.
11. Shaque S. Thalidomide—an overview and the
species-specic teratogenicity. Res J Congenit Dis.
2019;2:1.
12. McBride WG. Thalidomide and congenital abnormalities. Lancet. 1961;2(1358):90927–8.
13. Mohamed IN. Pharmacovigilance and reporting adverse drug reactions. Med Health.
2014;9(2):92–102.
14. Edwards IR. An agenda for UK clinical pharmacology: pharmacovigilance. Br J Clin Pharmacol.
2012;73(6):979–82.
15. Mann RD. An instructive example of a longlatency adverse drug reaction—sclerosing peritonitis due to practolol. Pharmacoepidemiol Drug Saf.
2007;16(11):1211–6.
16. Goldkind L, Laine L. A systematic review of
NSAIDs withdrawn from the market due to
hepatotoxicity: lessons learned from the bromfenac experience. Pharmacoepidemiol Drug Saf.
2006;15(4):213–20.
17. Solomon DH, Avorn J.Coxibs, science, and the public trust. Arch Intern Med. 2005;165(2):158–60.
18. Platt R, Brown JS, Robb M, McClellan M, Ball R,
Nguyen MD, Sherman RE.The FDA sentinel initiative—an evolving national resource. N Engl J Med.
2018;379(22):2091–3.
19. Syrowatka A, Song W, Amato MG, Foer D, Edrees
H, Kuznetsova M, Dulgarian S, Seger DL, Simona
A, Bain PA, Jackson GP. Key use cases for articial intelligence to reduce the frequency of adverse
drug events: a scoping review. Lancet Digital Health.
2022;4(2):e137–48.
20. Freidman MA, etal. The safety of newly marketed
approved medicines: do recent market removals mean
there is a problem? JAMA. 1999;281(18):1728–34.
21. Santoro A, Genov G, Spooner A, Raine J, Arlett
P. Promoting and protecting public health: how the
European Union pharmacovigilance system works.
Drug Saf. 2017;40:855–69.
22. Park JE, Yi J, Kwon O.Twenty years of traditional
and complementary medicine regulation and its
impact in Malaysia: achievements and policy lessons. BMC Health Serv Res. 2022;22(1):1–3.
23. Tsintis P, La Mache E.CIOMS and ICH initiatives in
pharmacovigilance and risk management: overview
and implications. Drug Saf. 2004;27:509–17.
24. Aronson JK, Ferner RE.Clarication of terminology
in drug safety. Drug Saf. 2005;28(10):851–70. https://
doi.org/10.2165/00002018- 200528100- 00003.
25. World Health Organization. International drug monitoring: the role of national centres. Technical report
series no. 498. Geneva: WHO; 1972.
26. Council for International Organizations of Medical
Sciences (CIOMS). CIOMS cumulative pharmacovigilance glossary, Geneva, Switzerland. 2021.
https://cioms.ch/wp- content/uploads/2021/03/
CIOMS- Cumulative- PV- Glossary- v1.0.pdf.
Accessed 12 Aug 2022.
27. International Council for Harmonisation of Technical
Requirements for Pharmaceuticals for Human Use.
ICH Topic E 2 A clinical safety data management:
denitions and standards for expedited reporting.
1995. Available at: https://www.ema.europa.eu/
en/documents/scientific- guideline/internationalconference- harmonisation- technical- requirementsregistration- pharmaceuticals- human- use_en- 15.pdf.
Accessed 3 Aug 2022.
28. European Medicine Agency. Eudravigilance—
European database of suspected adverse drug reaction reports. 2001. https://www.adrreports.eu/en/
glossary.html#. Accessed 28 Nov 2023.
29. US Food and Drug Administration. CFR—Code
of Federal Regulations Title 21. 2023. https://
www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
cfrsearch.cfm?fr=201.57. Accessed 28 Nov 2023.
30. Health Canada—Canada Vigilance Program. The
guidance document for industry—reporting adverse
reactions to marketed health products. 2009. https://
publications.gc.ca/collections/collection_2009/schc/H164- 33- 2009E.pdf. Accessed 28 Nov 2023.
31. American Society of Hospital Pharmacy. ASHP
guidelines on adverse drug reaction monitoring
and reporting. Am J Health Syst Pharm (AJHP).
1995;52(4):417–9. https://doi.org/10.1093/
ajhp/52.4.417.
32. Schatz SN, Weber RJ. Adverse drug reactions.
PSAP. 2015. Available at: https://www.accp.com/
docs/bookstore/psap/2015B2.SampleChapter.pdf.
Accessed 3 Aug 2022.
33. Krska K, Cox AR. Adverse drug reactions. In:
Whittlesea K, Hodson K, editors. Clinical pharmacy
and therapeutics. 6th ed. Oxford: Elsevier; 2019.
34. European Medical Writers Association.
Pharmacovigilance glossary. 2017. https://
www.emwa.org/media/2640/pv- sig- glossaryaugust- 2017.pdf. Accessed 22 Aug 2022.
35. European Medicine Agency. Clinical safety data
management: denitions and standards for expedited reporting. 1995. https://www.ema.europa.eu/
en/documents/scientific- guideline/internationalconference- harmonisation- technical- requirementsregistration- pharmaceuticals- human- use_en- 15.
pdf.
1 Introduction toDrug Safety andPharmacovigilance
27
36. World Health Organization. Safety monitoring of
medicinal products—reporting system for the general public. 2012. 9789241503198-eng.pdf (who.
int). Accessed 12 Nov 2023.
37. World Health Organization. Serious AEFI. 2018.
https://www.who.int/groups/global- advisorycommittee- on- vaccine- safety/topics/aefi/seriousae#cms. Accessed 1 Dec 2023.
38. National Coordinating Council for Medication
Error Reporting and Prevention. Medication errors.
2023. Available at: https://www.nccmerp.org/about- -
medication- errors. Accessed 13 Nov 2023.
39. Rawlins MD.Adverse reactions to drugs. Br Med J.
1981;282:974–6.
40. Edwards IR, Aronson JK. Adverse drug reactions:
denitions, diagnosis, and management. Lancet
(London, England). 2000;356(9237):1255–9.
https://doi.org/10.1016/S0140- 6736(00)02799- 9.
41. Aronson JK, Ferner RE. The law of mass action
and the pharmacological concentration-effect curve:
resolving the paradox of apparently non-doserelated adverse drug reactions. Br J Clin Pharmacol.
2016;81(1):56.
42. Aronson JK, Ferner RE. Joining the DoTS: new
approach to classifying adverse drug reactions. BMJ
(Clinical research ed). 2003;327(7425):1222–5.
https://doi.org/10.1136/bmj.327.7425.1222.
43. Dipiro CV.Obesity. In: Schwinghammer TL, Dipiro
JT, Ellingrod VL, Dipiro CV, editors. Dipiro’s pharmacotherapy handbook. 12th ed. McGraw Hill;
2023. p.657–6.
44. Lee SJ, Kavanaugh A.Adverse reactions to biologic
agents: focus on autoimmune disease therapies. J
Allergy Clin Immunol. 2005;116(4):900–5. https://
doi.org/10.1016/j.jaci.2005.03.028.
45. Pichler WJ. Adverse side-effects to biological
agents. Allergy. 2006;61(8):912–20. https://doi.
org/10.1111/j.1398- 9995.2006.01058.
46. Ditto AM.Drug allergy part A: introduction, epidemiology, classication of adverse reactions, immunological basis, risk factors, evaluation of patients
with suspected drug allergy, patient management
considerations. In: Grammer LC, Greenberger
PA, editors. Patterson’s allergic diseases. 6th ed.
Philadelphia: Lippincott, Williams & Wilkins; 2002.
p.295–334.
47. Greenberger PA. Drug allergy. J Allergy Clin
Immunol. 2006;117(2 Suppl Mini-Primer):S464–70.
https://doi.org/10.1016/j.jaci.2005.11.002.
48. European Commission Enterprise and Industry
Directorate-General. A guideline on summary of
product characteristics. Revision 2. 2009. https://
health.ec.europa.eu/system/files/2016- 1/smpc_
guideline_rev2_en_0.pdf. Accessed 12 Nov 2023.
49. International Council for Harmonisation of Technical
Requirements for Pharmaceuticals for Human Use.
Medical dictionary. 2023. https://www.meddra.org/
about- meddra/history. Accessed Aug 2022.
50. Uppsala Monitoring Centre. WHO-ART legacy service. 2023. https://who- umc.org/vigibase/vigibase-
services/who- art/. Accessed 19 Nov 2023.
51. World Health Organisation. International Statistical
Classication of Diseases and Related Health
Problems (ICD). https://www.who.int/standards/
classications/classication-of-diseases. Accessed
on 24 th February 2024.
52. SNOMED International. SNOMED CT. 2022.
Available at: https://www.snomed.org/. Accessed 5
Aug 2022.
53. Council for International Organizations of
Medical Sciences (CIOMS). Reporting adverse
drug reactions. Denition of terms and criteria
for their use. 1999. https://cioms.ch/wp- content/
uploads/2017/01/reporting_adverse_drug.pdf.
Accessed 5 Aug 2022.
54. Lagerlund O, Strese S, Fladvad M, Lindquist
M.WHODrug: a global, validated and updated dictionary for medicinal information. Ther Innov Regul
Sci. 2020;54(5):1116–22. https://doi.org/10.1007/
s43441- 020- 00130- 6.
55. Uppsala Monitoring Centre. WHO-drug global.
2022. Available at: https://who- umc.org/whodrug/
whodrug- global/. Accessed 5 Aug 2022.
56. European Medicine Agency. Electronic submission
of medicinal product information by marketingauthorisation holders Article 57 (2) of Regulation
(EC) No 726/2004. Available at https://www.ema.
europa.eu/en/documents/other/electronic-submission-medicinal-product-information-marketingauthorisation-holders_en.pdf. Accessed on 14 th
May 2024.
57. Pirmohamed M, Breckenridge AM, Kitteringham
NR, Park BK. Adverse drug reactions. BMJ (Clin
Res Ed). 1998;316(7140):1295–8. https://doi.
org/10.1136/bmj.316.7140.1295.
58. European Medicine Agency. Guideline on key
aspects for the use of pharmacogenomics in
the pharmacovigilance of medicinal products.
2015. https://www.ema.europa.eu/en/documents/
scientific- guideline/guideline- key- aspects- usepharmacogenomics- pharmacovigilance- medicinalproducts_en.pdf. Accessed 22 Aug 2022.
59. Schwab M, Schaeffeler E.Pharmacogenomics: a key
component of personalized therapy. Genome Med.
2012;4(11):93. https://doi.org/10.1186/gm394.
60. Dere WH, Suto TS. The role of pharmacogenetics and pharmacogenomics in improving translational medicine. Clin Cases Miner Bone Metab.
2009;6(1):13–6.
61. Rawlins M.De Testimonio: on the evidence for decisions about the use of therapeutic interventions. Clin
Med (Lond). 2008;8(6):579–88.
62. Borgerson K. Valuing evidence: bias and the evidence hierarchy of evidence-based medicine.
Perspect Biol Med. 2009;52(2):218–33. https://doi.
org/10.1353/pbm.0.0086.
Соседние файлы в папке Библиотека им академика М.И. Перельмана