Part I:  Policy and economic issues Part II:  Pharmaceutical management Part III:  Management support systems

Selection
Procurement
Distribution
Use
27  Managing for rational medicine use
28  Investigating medicine use
29  Promoting rational prescribing
30  Ensuring good dispensing practices
31  Community-based participation and initiatives
32  Drug seller initiatives
33  Encouraging appropriate medicine use by consumers
34  Medicine and therapeutics information
35 Pharmacovigilance

chap ter 35
Pharmacovigilance

Summary  35.2 illustrations
35.1 What is pharmacovigilance and why is it Figure 35-1 Analysis of medication errors in a U.S. hospital,
important?  35.2 2005  35.4
Adverse drug reactions  •  Medication errors  •  Figure 35-2 Relationship of medication safety terms   35.6
Adverse drug events Figure 35-3 Pharmacovigilance and the pharmaceutical
management framework  35.7
35.2 Designing a pharmacovigilance system   35.6 Figure 35-4 The pharmacovigilance framework   35.8
Pharmacovigilance activities at the facility level  •  Figure 35-5 Nonvoluntary data collection tool for
Pharmacovigilance activities at the national level  •  pharmacovigilance   35.12
Pharmacovigilance activities as part of public health Figure 35-6 Sample ADE/product quality problem form from
programs  •  Pharmacovigilance activities at the Zambia  35.13
international level
Table 35-1 Definitions of terms related to
35.3 Data collection  35.10 pharmacovigilance  35.3
Passive data collection  •  Mandatory data collection  •  Table 35-2 Determining ADR probability using
Active data collection  •  Data collection tools indicators  35.3
35.4 Data analysis and reporting   35.11 Table 35-3 Dangerous abbreviations   35.5
Table 35-4 Roles and responsibilities of partners in
35.5 Taking actions for improvement   35.15
pharmacovigilance  35.9
References and further readings   35.16 Table 35-5 Severity index for medication errors   35.14
Assessment guide  35.18
b oxes
Box 35-1 Medication error caused by sound-alike
products  35.4
Box 35-2 Determining whether a medication error
occurred  35.14
Box 35-3 Safe medication practices   35.16

c ountry studies
CS 35-1 Implementing an ADR reporting system in
India  35.15
CS 35-2 Standard operating procedures for aggregating
ADR data and taking appropriate action in an ART
program in Kenya   35.17

copyright © management sciences for health 2012

35.2 U SE

s u mm a r y
Poor product quality, adverse drug reactions (ADRs), activities are carried out at the facility, national, and
and medication errors greatly influence health care sys- international levels and require collaboration among a
tems by negatively affecting patient care and increasing wide range of partners with differing responsibilities.
costs. Most of the statistics documenting the issues and National governments are responsible for ensuring that
highlighting the importance of pharmacovigilance come medicines sold in their countries are of good quality, safe,
from developed countries, therefore low- and middle- and effective. An important component of a country’s
income countries likely have greater problems because ability to monitor pharmaceutical safety is a national
of the poorer state of their health system infrastructure, pharmacovigilance system that is supported by the drug
the unreliable supply and quality of medicines, the lack regulatory authority. However, some countries have not
of adequately trained essential health care staff, and their included pharmacovigilance as part of their legal frame-
limited access to communication and information tech- work. Public health programs, such as those for treating
nology. HIV/AIDS and malaria, may have separate pharmaco-
vigilance systems, while hospitals usually have the capac-
Three areas of pharmacovigilance include—
ity to design and implement facility-based medication
• Product quality safety activities.
• Adverse drug reactions
The major components of a pharmacovigilance system
• Medication errors
are data collection, which can be passive, active, or man-
Product quality problem reporting systems are covered datory, and data analysis and reporting. When ADEs
in Chapter 19 on quality assurance. This chapter focuses occur, they must be analyzed and reported and their
on the importance of ADRs and medication errors and significance must be communicated effectively to an
actions to take to minimize their impact. An ADR is audience that has the knowledge to interpret the infor-
a harmful response caused by the medicine after the mation, including the national pharmacovigilance center,
patient has received it in the recommended manner; if one exists, and the World Health Organization (WHO)
whereas, adverse drug events (ADEs) result from either Programme for International Drug Monitoring. Based
the medicine itself or the medicine’s inappropriate use or on the results of the analysis, actions should be carried
medication error. out to reduce adverse drug events and thereby improve
patient care. To encourage continued participation in
Health professionals may still think of pharmaco-
the process, interventions should be shared with the data
vigilance strictly in terms of identifying and reporting
reporters. Follow-up data collection and analysis can
previously unknown and serious ADRs related to new
then measure the effectiveness of the interventions.
products; however, pharmacovigilance activities are
related to every sector of the pharmaceutical manage- The use of medicines involves a trade-off between bene­
ment framework: selection, procurement, distribution, fits and the potential for harm. Pharmacovigilance can
use, management support, and the overarching policy help minimize harm by ensuring that medicines of good
and legal framework. Likewise, pharmacovigilance quality are used rationally.

35.1 What is pharmacovigilance and why is almost impossible because most cases go undetected.
is it important? Much of the documented evidence available on medicine
quality and ADEs comes from industrialized countries.
WHO defines pharmacovigilance as “the science and activi- For example, in a bellwether report, the U.S. Institute of
ties relating to the detection, assessment, understanding and Medicine (IOM 2000) estimated that 7,000 or more people
prevention of adverse effects or any other medicine-related die each year from medication errors and ADRs and that
problem” (WHO 2004, 1). Terms related to the science of the total costs may be between 17 billion U.S. dollars (USD)
pharmacovigilance are defined differently in different set- and USD 29 billion per year in hospitals nationwide. A
tings and by different organizations. The terms used in this follow-up report estimated that more than 1.5 million
chapter are defined in Table 35-1. Americans are injured every year by medication errors in
More and more evidence is showing the huge effect of hospitals, nursing homes, and doctor’s offices (IOM 2006).
poor product quality, ADRs, and medication errors on ADEs also are costly in terms of loss of trust in the health
health care, but estimating the actual scale of this effect care system by patients.
 35  /  Pharmacovigilance 35.3

Table 35-1 Definitions of terms related to pharmacovigilance

Terms Definition Example

Harm occurred
Adverse drug event Harm caused by the use of a drug Heart arrhythmia from discontinuing atenolol
(whether or not it was considered an error)
Adverse drug reaction Harm caused by the use of a drug at normal doses Skin rash from nevirapine
Harm may have occurred
Medication error Preventable event that may cause inappropriate use Failure to renew prednisone order on transfer to
of a drug or patient harm medical ward
Harm did not occur
Potential adverse drug event Circumstances that could result in harm by the use Receipt of another patient’s ampicillin, with no
of a drug but did not harm the patient resulting effect
Source: Adapted from Nebeker, Barach, and Samore 2004.

Compared with that in high-income countries, the situ- sometimes expired or are close to expiration or have been
ation in low-and middle-income countries is likely more stored under conditions that adversely affect their quality.
urgent because of the poorer state of health system infra- See Chapter 15 for more information about ensuring the
structure, the unreliable supply and quality of medicines, quality of medicine donations.
and the lack of adequately trained essential health care staff. This chapter focuses on the importance of ADRs and
Three areas of pharmacovigilance include— medication errors and actions to take to minimize them.

• Product quality Adverse drug reactions

• Adverse drug reactions
• Medication errors An ADR is a harmful response in the patient caused by
the drug itself given in the recommended manner (dose,
Quality issues relate to pharmaceutical products that frequency, route, administration technique). Examples
are defective, deteriorated, or adulterated because of poor include allergic reactions, effects from withdrawal, or
manu­facturing practices, inadequate distribution and stor- reactions caused by interactions with other medications.
age, poor labeling, or tampering. Counterfeit products WHO defines a serious ADR as any reaction that is fatal,
would fall under this category, for example, as would medi- life-threatening, or permanently or significantly disabling;
cines that have lost their potency after being stored at high requires or prolongs hospitalization; or relates to misuse or
temperatures. These quality assurance issues, including dependence (WHO/UMC 2000).
product problem reporting systems, are covered in detail When a new medicine is being developed, it goes through
in Chapter 19. In addition, pharmaceutical donations have several phases of testing, first with animals, then with human

Table 35-2 Determining ADR probability using indicators

Probability scale: indicators Yes No Don’t know

1. Are there previous conclusive reports on this ADR? +1 0 0
2. Did the ADR appear after the suspected drug was administered? +2 −1 0
3. Did the ADR improve when the drug was discontinued or a specific antidote was administered? +1 0 0
4. Did the ADR reappear when the drug was readministered? +2 −1 0
5. Could alternative causes (other than the drug) have caused the ADR on their own? −1 +2 0
6. Was the drug detected in the blood (or other fluids) in a concentration known to be toxic? +1 0 0
7. W
 as the ADR more severe when the dose was increased or less severe when the dose was
decreased? +1 0 0
8. Did the patient have a similar ADR to the same or similar drugs in any previous exposure? +1 0 0
9. Did any objective evidence confirm the ADR? +1 0 0
Total score = ____________   Possible = 0–4  Probable = 5–8  Definite = >9
Source: Naranjo et al. 1981.
35.4 U SE

Figure 35-1 Analysis of medication errors in a U.S. hospital, 2005

30
Storage Prescribing Dispensing Administration Monitoring

25

January 2005
20 March 2005
Number of errors

June 2005

15

10

0
ro cine -

ge

ns

ly

ly

ly

ug

ed

vi ng

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i d

ro

ro

tim
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ct

ct

ct

sp rin
Im ed un

tio
ra

itt

ls

se
dr
er

er

nt ori
ib

rit

rre

rre

rre

ta
to

re to
om
m /so

ia

ng
cr

ng
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ry
w

tie it
co

co

co
rs

i
ev

tio
es

nd

ap f pa mon

of on
nt

ro
ike ke

ro

ug
in

in

in
pe

br
pr

rip

re

W
ha

m
W
al -ali

d
ab

Dr
te

e
sc

te
de

le

le
or

t
ok

t
ria

pu
an
of

Fil

be

ria

ria
Po

un
Lo

op

Tr

o
e

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op

op
po
Us

Co
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pr

pr
m
ap

ap
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In

In

In
Source: Chris Olson, unpublished data.

volunteers, for safety and efficacy. However, when a product

is approved, it may have been tested in only thousands of Box 35-1
patients—many fewer than are likely to use the product once Medication error caused by sound-alike
it is approved for sale on the market. Therefore, the informa- products
tion on effects generated in premarketing studies is incom-
Nurses and pharmacists at a hospital reported two
plete relative to the full complement of likely users, making
cases where RECOMBIVAX HB (hepatitis B vac-
postmarketing surveillance an important tool for complet-
cine, recombinant) was given to newborns instead
ing the safety and efficacy profile of a drug product (Ahmad
of Comvax (hemophilus B conjugate vaccine with
2003).
hepatitis B vaccine). When a telephone order was mis-
Because it includes so many more people than are included
understood, the wrong product was administered to
in the premarketing surveillance process, postmarketing
the patients. Nurses in the unit felt this same error had
surveillance should be able to detect rare but serious adverse
probably occurred other times without anyone notic-
reactions; chronic toxicity; effects in sensitive groups, such
ing. A safe medication practice to prevent sound-alike
as children, pregnant women, and the elderly; and inter­
product name errors is to transcribe and read back
actions with other pharmaceuticals, herbal medicines, or
verbal orders. Face-to-face verbal orders should be
food. Often, however, linking an ADR with a specific medi-
accepted only in emergencies or when the prescriber is
cine is difficult; for example, an ADR can occur long after a
physically unable to write the order.
medication is administered, which makes confirming the
cause a challenge. See Table 35-2 for ways to analyze prob- Source: ISMP 2003.
able causality.

Medication errors
of thirty-six health care facilities in the United States showed
The National Coordinating Council for Medication Error that nearly one in five doses of medication was given in
Reporting and Prevention defines medication error as “any error, and 7 percent had the potential to cause patient harm
preventable event that may cause or lead to inappropriate (Barker et al. 2002).
medication use or patient harm while the medication is in Medication errors are caused by faulty systems, processes,
the control of the health care professional, patient, or con- and conditions that lead people to make mistakes or fail
sumer” (http://www.nccmerp.org/aboutMedErrors.html). to prevent mistakes (Figure 35-1). For example, stocking
Errors can be harmless or detrimental to the patient. A study wards in hospitals with certain concentrated solutions, even
 35  /  Pharmacovigilance 35.5

Table 35-3 Dangerous abbreviations

Abbreviation Intended meaning Common error Preferred term

U Units Mistaken as a 0 (zero) or a 4 (four), resulting Write unit.
in overdose. Also mistaken for cc (cubic
centimeters) when poorly written.
µg Micrograms Mistaken for mg (milligrams), resulting in a Write mcg.
one-thousand-fold overdose.
Q.D. Latin abbreviation for every The period after the Q has sometimes been Write daily.
day mistaken for an I, and the drug has been
given QID (four times daily) rather than daily.
Q.O.D. Latin abbreviation for every Misinterpreted as QD (daily) or QID (four Write every other day.
other day times daily). If the O is poorly written, it looks
like a period or an I.
SC or SQ Subcutaneous Mistaken as SL (sublingual) when poorly Write subcutaneous or subcut.
written.
TIW Three times a week Misinterpreted as three times a day or twice Write specific days for administration,
a week. for example, MON., WED., and FRI.
D/C Discharge; also discontinue Patient’s medications have been prematurely Write discharge or discontinue.
discontinued when D/C (intended to
mean discharge) was misinterpreted as
discontinue, because it was followed by a list
of drugs.
HS Half strength Misinterpreted as the Latin abbreviation HS Write half strength.
(hour of sleep).
cc Cubic centimeters Mistaken as U (units) when poorly written. Write ml or mL or mls for milliliters.
AU, AS, AD Latin abbreviation for both Misinterpreted as the Latin abbreviation OU Write ear.
ears; left ear; right ear (both eyes); OS (left eye); OD (right eye).
Lack of a leading Decimal point is missed, resulting in a Always lead with a zero before a decimal
zero (.X mg) dosage error of tenfold or greater. point (0.X mg).
or Never follow a whole number with a
Use of a trailing decimal point and zero (X mg).
zero (X.0 mg)
@ at Mistaken as zero. Write at.
MS, MSO4 Morphine sulfate, Confused for each other. Write morphine sulfate or
MgSO4 magnesium sulfate magnesium sulfate.
IU International Unit Mistaken as IV (intravenous) or 10 (ten). Write international unit.
Source: http://www.nccmerp.org/dangerousAbbrev.html.

though they are toxic unless diluted, has resulted in deadly ADE, but an ADE might include the result of an overdose
errors. Other problems can result from illegible handwriting, because of a dispensing error or some other error occurring
use of dangerous abbreviations (Table 35-3), overlooked during the medication-use process. (See Figure 35-2.)
interactions with other medicines, and verbal miscommu- Medication-usage patterns strongly influence the inci-
nications and sound-alike or look-alike products. Box 35-1 dence of ADEs. For example, injectable medications are
describes a case where the wrong medicine was adminis- more commonly used in developing countries, and they are
tered to babies because of a misunderstood verbal order. more likely to be associated with ADEs (WHO/UMC 2002).
Medication errors, by definition, should be preventable In addition, self-medication, lack of regulatory control over
through education and effective systems controls involving the sale of medicines, and irrational prescribing all contrib-
pharmacists, prescribers, nurses, administrators, regulators, ute to the incidence of ADEs.
and patients. ADEs are preventable when they are the result of a medi-
cation error (discussed below) or nonpreventable, as would
Adverse drug events be the result of an unknown allergy. A potential ADE could
include an error that may or may not reach the patient but
An ADE is a harmful response that is caused by a drug or the does not cause harm, such as a dispensing error that was dis-
inappropriate use of a drug. Therefore, an ADR is always an covered and avoided at the last minute. The documentation
35.6 U SE

Figure 35-2 Relationship of medication safety terms

45 children crippled
by poorly administered Adverse clinical events
injections in Uganda

Adverse
drug
Medication reactions
errors

120 people die from ART patients develop

taking adulterated Counterfeit zidovudine-associated
cough syrup in Panama or substandard anemia in Namibia
products

Sources: SPS 2009, figure 1, adapted from Barker et al. 2002; Ferner and Aronson 2006; Nebeker, Barach, and Samore 2004.

of ADEs and ADRs is important—especially in new prod- priority safety concerns, such as the use of registries, sen-
ucts—where such postmarketing information can result tinel sites, and follow-up of defined patient cohorts. Other
in changes to the recommended usage, product packaging system expansion efforts can include establishing a link
or labeling, or even a recall. Identifying and documenting between pharmaceutical quality assurance and ADR moni-
potential ADEs is useful because this can identify problem toring and developing mechanisms to communicate medi-
areas that might be corrected, such as a communication cine safety information to health care professionals and the
problem within the health facility or two medicines with public.
similar names being stored next to and therefore confused A country’s pharmacovigilance system should incor-
with each other. porate activities and resources at the facility, national, and
international levels and foster collaboration among a wide
range of partners and organizations that contribute to
35.2 Designing a pharmacovigilance system ensuring medicine safety. Figure 35-4 illustrates the com-
ponents of a comprehensive, ongoing pharmacovigilance
Health professionals may still think of pharmacovigilance system with functions for monitoring, detecting, reporting,
strictly in terms of identifying and reporting previously evaluating, and documenting medicine safety data as well as
unknown and serious ADEs related to new products; how- intervening and gathering information from and providing
ever, pharmacovigilance activities are related to every sector educational feedback to the reporters—prescribers, health
of the pharmaceutical management cycle. Figure 35-3 shows care workers, other health care professionals, and consum-
examples of the relationship between pharmacovigilance ers. When the information has been collected, evaluators,
and pharmaceutical management. such as epidemiologists or pharmacologists, should analyze
Although many national pharmacovigilance programs it to determine the adverse event’s severity, probable causal-
are largely based on ADE reporting, a comprehensive sys- ity, and preventability.
tem should encompass monitoring of medication errors Significant data must be communicated effectively to a
and therapeutic ineffectiveness (related to poor treatment structure or entity that has the authority to take appropriate
adherence, antimicrobial resistance, product quality prob- action, whether at the facility, national, or even international
lems, inappropriate use, or interactions); product qual- level. The entity may be a hospital’s drug and therapeutics
ity problems; and communication of such information to committee, the national pharmacovigilance center, if one
health care professionals and consumers for risk-benefit exists, or the WHO Programme for International Drug
decision making (SPS 2009). For example, as a pharmaco- Monitoring. The final function in the framework is appro-
vigilance system matures, it may expand from a program priate action. If data are collected, analyzed, and reported,
based strictly on passive ADE surveillance that relies on but no one takes any action based on the data, the system
voluntary reports from health care providers or consum- is irrelevant. The risk reduction action may be regulatory
ers to incorporate active surveillance methods to address (withdrawing marketing authorization, recalling a medica-
 35  /  Pharmacovigilance 35.7

Figure 35-3 Pharmacovigilance and the pharmaceutical management framework

Selection

Use Management support Procurement

Distribution

Policy, law, and regulation

Pharmacovigilance Detection within the pharmaceutical

activity management framework Prevention
Product quality • Most product quality issues are detected in • Prequalify suppliers during procurement.
the distribution portion of the pharmaceutical • Establish a pharmaceutical quality assurance program.
management cycle. • Establish a policy and legal framework that addresses
• Physical inspection is done at the time of receiving pharmaceutical quality.
the product from the supplier and at other points of • Enforce laws and regulations related to product
distribution to the patient. quality.
• Complaints about efficacy occur during use.
ADRs • Management support functions, such as surveillance • Consider ADR information during the selection
and monitoring systems, during use are the primary process to make formulary decisions and establish
methods for detecting ADRs. standard treatment guidelines.
• Report ADRs to the appropriate parties at the facility,
national, and international levels.
• Train health professionals about ADRs.
• Communicate with patients about ADRs.
Medication errors • Errors can be detected in all phases of the Prevention strategies should focus on all processes—
pharmaceutical management cycle: ordering, storing, • Promote a culture of safety through a nonpunitive
labeling, compounding, dispensing, transcribing, environment for reporting events.
prescribing, administering, and monitoring. • Improve availability of drug information.
• Train and educate staff.
• Consider past and potential errors when selecting
products or a formulary.
• Issue prescribing guidelines.
• Establish dispensing and administration procedures
and safeguards.
• Establish monitoring guidelines.
• Improve written and oral communication.
• Involve patient and family in care plan.
Source: CPM/MSH 2011.

tion); managerial (revising a hospital formulary, instituting The outcome of a pharmacovigilance system should be
distribution controls); or educational (teaching prescribers decreased medicine-related problems with the ultimate
about medicine-medicine interactions or proper product effect being a reduction in morbidity and mortality.
handling). To encourage continued participation in the pro- As mentioned, pharmacovigilance activities are carried
cess, interventions should be shared with the data report- out at the facility, national, and international levels and
ers as part of a feedback loop. Follow-up data collection and require collaboration among a wide range of partners with
analysis will then measure the effectiveness of the interven- differing responsibilities (Table 35-4). To plan for this infor-
tions. mation system, basic questions must be answered about
35.8 U SE

Figure 35-4 The pharmacovigilance framework

People Functions Structures
Reporters Reporting (detection and generation) Manufacturers
Doctors Report suspected side effects, adverse events, quality concerns, Hospitals/Institutions
Pharmacists and errors
Nurses
Other health care workers
Consumers

Evaluators Data collation (evaluation) Pharmacovigilance center

Medical specialists Collate data, conduct initial analysis Drug and therapeutics
Clinical pharmacologists Causality analysis and risk determination committees (DTCs)
Pharmacists Establish causality or determine if further epidemiologic studies Safety advisory
are required to establish association committees
Epidemiologists

Decision making and appropriate action Regulatory authority

Package insert amendments, warnings, scheduling changes, Industry
risk management, market withdrawal, product recall Health services
Professional groups
Advisory committees

Prevented medicine-related problems  |  Reduced morbidity and mortality

Source: CPM/MSH 2011.

whether the data flow will be separate for each area of phar- with hospital care are high and strategies for improvement
macovigilance or combined, who will be responsible for are better documented. But many ADEs occur in other
the data collection and reporting at each level of the health health care settings, such as physicians’ offices, nursing
system, and whether vertical public health programs will be homes, pharmacies, and patients’ homes. However, under-
separated or integrated. For example, will the responsibility reporting of ADEs is a critical problem in all health care
for pharmacovigilance fall under the drug and therapeutics settings.
committee (or pharmacy and therapeutics committee) at the Even if a country lacks the infrastructure for coordinat-
facility level? How will pharmacovigilance drive decisions ing national pharmacovigilance activities, hospitals usually
for formulary selection and treatment guidelines, changes have the capacity to design and implement a facility-based
in policies and procedures at different levels, and product pharmacovigilance system. Effective systems for pharmaco-
approval and pharmaceutical regulation? These questions vigilance and promoting safe medication practices generally
may be easier to answer if the country has a national phar- fall under the purview of the drug and therapeutics com-
macovigilance system in place—or individual facilities mittee.
developing their own systems may need to create the best Hospital-based reports of ADRs make important con-
information management system based on their own orga- tributions to clinical experience and improving the under-
nization. standing of pharmacotherapy. In addition, the assessment
of ADEs gives facilities the information necessary to reduce
Pharmacovigilance activities at the facility level medication errors and improve health care for patients.

Medication safety monitoring is an important part of high- Pharmacovigilance activities at the national level
quality health care in health facilities, especially hospitals.
A U.S.-based study showed that ADEs in hospitalized National governments are responsible for ensuring that
patients resulted in significant health and economic con- medicines sold in their countries are of good quality, safe,
sequences (Classen et al. 1997). Monitoring and reporting and effective. An important component of a country’s abil-
of medication errors and ADRs are important aspects of ity to monitor pharmaceutical safety is a national pharma-
a hospital’s safety system; consequently, most evidence of covigilance system that is supported by the drug regulatory
ADEs comes from hospitals, because the risks associated authority (see Chapters 6 and 19).
 35  /  Pharmacovigilance 35.9

Table 35-4 Roles and responsibilities of partners in pharmacovigilance

Partner Responsibilities
Government • Establish national pharmacovigilance system
• Develop regulations for medicine monitoring
• Provide up-to-date information on adverse reactions to professionals and consumers
• Monitor effect of pharmacovigilance through indicators and outcomes
Industry • Provide quality medicines of assured safety and efficacy
• Assess and share ADRs that are reported
Hospitals • Promote the incorporation of pharmacovigilance into procedures and clinical practice
Academia • Teach, train, conduct research, and develop policy about pharmacovigilance
• Include pharmacovigilance in curriculum
Medical and pharmaceutical professional • Provide training and awareness to health professionals regarding pharmacovigilance
associations
Poisons and medicines information centers • Provide information on medication safety and pharmacovigilance
• Collaborate with national pharmacovigilance centers, if applicable
Health professionals (including physicians, • Detect, investigate, manage, and report ADRs, medication errors, and product quality concerns
nurses, pharmacists, dentists) • Counsel patients about ADRs
Patients and consumers • Understand to the extent possible their own health problems and participate in the treatment
plan by following medication instructions
• Report adverse reactions to health professionals as well as concomitant use of other
medications, including traditional medicine
Media • Create awareness in the community about the safe use of medicines

National pharmacovigilance centers are responsible for— Pharmacovigilance activities as part of public health
programs
• Promoting the reporting of ADEs
• Collecting case reports of ADEs Depending on how their public health systems are organized,
• Clinically evaluating case reports countries may have public health initiatives that are disease-
• Collating, analyzing, and evaluating patterns of specific and operate separately from the primary health
ADEs system (for example, HIV/AIDS, tuberculosis, malaria, vac-
• Promoting policies and interventions that help prevent cinations), also known as vertical health programs. Such ver-
medication errors tical programs depend on good pharmacovigilance practices
• Determining what case reports constitute true adverse (WHO/UMC 2006). Monitoring ADRs is especially impor-
reactions to medications tant when treatment is being scaled up, such as antiretroviral
• Recommending or taking regulatory action in therapy (ART) for HIV/AIDS, or if a change is being made
response to findings supported by good evidence in the standard treatment guidelines, such as switching to
• Initiating studies to investigate significant suspect artemisinin-based combination therapies for malaria.
reactions The major aims of pharmacovigilance in public health ini-
• Alerting prescribers, manufacturers, and the public to tiatives are the same as those of the national pharmacovigi-
new risks of adverse events lance system. The structure and organization of the existing
• Sharing their reports with the WHO Programme for national systems will help determine how the public health
International Drug Monitoring (WHO/UMC 2006) program pharmacovigilance efforts should be designed. In
some cases, the country may not have a national pharma-
A national pharmacovigilance system can be housed covigilance system. In that case, the public health program’s
in a national pharmacovigilance center or in a tertiary or system takes on additional importance and may provide a
research-oriented hospital. In the traditional model, a phar- model for the eventual establishment of a national system. In
macovigilance system was strongly centralized and con- Kenya, as ART programs scaled up and developed facility-
sisted of one national center collecting reports from health based ADR monitoring systems, the Ministry of Health rec-
professionals around the country. Many countries are mov- ognized the importance of national-level coordination and
ing toward a more decentralized system with a national cen- added pharmacovigilance to its responsibilities—a good
ter functioning as a focal point for regional or facility-based example of a bottom-up approach to incorporating pharma-
centers (WHO/UMC 2000). covigilance into the health care system.
35.10 U SE

WHO has a good resource on using pharmacovigilance establish a team approach to improving patient care and
as a tool in public health treatment programs (WHO/UMC reducing risks.
2006). Barriers to voluntary reporting of medication events are—

Pharmacovigilance activities at the international level • Fear of punishment by supervisors or fellow workers
(in the case of an error)
The patterns of how people access and use pharmaceuti- • Fear of liability for the provider or facility
cals are changing because of globalization, free trade, and • Failure to recognize that an incident has occurred
increased use of the Internet (WHO 2004). These changing • Unclear or cumbersome methods for reporting
patterns require that pharmacovigilance activities around • Poor track record of improvements by the institution
the world become more closely linked and therefore bet- • Lack of time
ter able to respond to how medicines are being used in
society. The objective of a successful monitoring system is to learn
At the international level, WHO initiated its Programme from and correct sources of error rather than to punish
for International Drug Monitoring in 1968 to pool exist- offenders. In addition to driving out fear, facilities should try
ing data on ADRs from ten countries. With its Uppsala to improve error tracking through education programs that
Monitoring Centre, the WHO program now works with promote voluntary reporting and by communication to staff
national pharmacovigilance programs in almost 100 coun- about the improvements resulting from medication events
tries (UMC 2010). The Uppsala Centre maintains the data- reported.
base of ADR reports—one of the largest in the world with
more than 5 million case reports. The Uppsala Centre estab- Mandatory data collection
lished standardized reporting by all national centers and
facilitates communication between countries on medicine Many country regulations require manufacturers and dis-
safety issues. tributors of pharmaceuticals to report information on ADRs
The Institute for Safe Medication Practices (http://www. that they gather during postmarketing surveillance to health
ismp.org) has established a forum for individual health authorities. In addition, facilities seeking accreditation may
care providers and consumers in any country to confiden- be required to have an ADE collection system in place as
tially share information on ADEs. Although the system part of the process to receive official recognition. Some
was established for U.S.-based reporting, the institute wel- countries require health care professionals to report ADEs,
comes reports from anywhere in the world. Health care but the effectiveness of such legislation is unknown (WHO/
professionals and consumers can submit reports and asso- UMC 2000).
ciated materials in confidence. After removing the iden-
tifiers, the information is shared with the U.S. Food and Active data collection
Drug Administration, the manufacturer, and others to
inform them about pharmaceutical labeling, packaging, Active data collection of medication events is carried out as
and nomenclature issues that may promote errors by their a focused and structured activity and includes trigger tools,
design. patient chart audits, and direct observation methods. Using
Major components of a pharmacovigilance system are a consistent methodology for active data collection provides
data collection, which can be voluntary or nonvoluntary, more reliable calculated medication event occurrence rates
and data analysis and reporting. and evidence of trends.
Trigger tools provide clues that an ADR occurred. Triggers
are identified from either computerized reports or manual
35.3 Data collection review methods to identify alerting orders, laboratory val-
ues, or clinical conditions. Further research into these trig-
Passive data collection gers may help identify ADRs that have occurred or that are
currently evolving—
Passive reporting of ADRs and medication errors (also
known as voluntary case reporting) requires health care Laboratory triggers are identified from defined parameters
providers to be active participants in a culture of safety. indicating an ADR might be associated (serum glucose
Programs relying solely on voluntary, spontaneous report- under 50, white blood cell count below 3,000, platelets
ing methods reveal only the tip of the iceberg, and calculated below 50,000, toxic drug levels, and the like).
medication event rates are more an indication of report- Medication order triggers are prescription orders for anti-
ing rates than actual occurrence rates. However, voluntary dotes or reversal agents such as dextrose 50 percent
reporting should always be encouraged, because it helps 50-mL injection, glucose tablets, diphenhydramine,
 35  /  Pharmacovigilance 35.11

steroids, naloxone, epinephrine, or sudden change or cies between the written order and the actual practice
stoppage of a patient’s medication (“discontinue digoxin, observed in terms of medication, dose, frequency,
quinidine, potassium chloride”). route, and so on.
Clinical triggers are patient conditions often associated with 3. The data are used to calculate error rates for a specific
ADRs, such as rash, falls, lethargy, or apnea. focus area, such as the ward or the facility. Rates or
trends may help identify problematic procedures or
Trigger detection methods yield more data than vol- areas for additional training.
untary reports (Jha et al. 1998), and more sophisticated
methods combine composite triggers (such as laboratory A study comparing three methods for detecting errors—
tests and medication orders) for better yields (Schiff et al. direct observation, chart review, or voluntary adverse event
2003). reporting—showed that direct observation was far more
Whereas trigger tools can help identify the patients and efficient and accurate in detecting medication errors (Flynn
medications most likely implicated in an event, chart review et al. 2002). Direct observation can also be used as a train-
is used to identify potential ADRs, medicine interactions, ing and orientation tool for new employees by ensuring that
and medication errors. These reviews can be conducted pro- new employees have a minimal level of competency and
spectively, concurrently, or retrospectively. Retrospective understand the facility’s medication administration process.
reviews are often more convenient for data collection,
although the time lapse since the event makes in-depth Data collection tools
investigation difficult. Medical records classified by codes,
such as ICD-10 (International Classification of Diseases, ADR and medication error data are usually collected by fill-
Tenth Revision) codes that indicate an ADR, provide a ing out a standardized form, thereby providing convenience
method to identify suspicious charts. and consistency. Data collection tools should be adapted
A prospective study might focus on recording any possible from standards of practice and procedures, and the data
adverse event in every patient receiving a new medicine. For fields on the form determined by how the data are eventually
instance, the Ghana National Centre for Pharmacovigilance summarized and used. Ideally, if a country has a national
developed a simple form for facilities to document and pharmacovigilance program, the reporting form is stan-
report ADRs in pregnant women associated with a change dardized for use in all settings throughout the country.
in recommended treatment from chloroquine to sulfa- For ADR data, identifying specifics about the patient is
doxine-pyrimethamine to prevent malaria (Dodoo 2005). important. These include concomitant therapies and condi-
Combined with their demographic information, the infor- tions, the patient’s reaction to the medicine, and the medi-
mation collected on this cohort of patients can provide an cine suspected of causing the reaction together with the
effective way of identifying previously unrecognized ADRs manufacturer and batch number, if available. WHO gives
(WHO/UMC 2000). Prospective and concurrent reviews guidance on what to include on a data collection form
can also detect potential adverse events before they happen (WHO 2002) (see also Box 6-2 on adverse drug reaction
or as they are evolving, so that patient harm can be avoided monitoring in Chapter 6).
or minimized. For medication error data, collecting information that can
Direct observation provides an abundance of useful data be analyzed for improvements to the medication-use system
on medication errors and helps to identify weaknesses in is important. Systems may have separate forms for tracking
the medication-use process. Observers can be placed at any product quality problems, ADRs, and medication errors, or
point in the medication-use process, but medication admin- systems may use one form and process. Figure 35-6 shows
istration is often one of the most problematic areas and easi- a sample ADE reporting form that also combines reporting
est to observe. If the data collection method is consistent, for product quality problems in Zambia.
the resulting error rates are reliable and allow improvements
to be measured. An example follows of the steps that could
comprise data collection using direct observation of the 35.4 Data analysis and reporting
medication administration process—
After the ADR data have been collected, they should be ana-
1. The observer follows randomly selected nurses as lyzed to determine severity, probable causality, and prevent-
they administer medications to patients on a hospital ability. Specific algorithms and classification systems have
ward. The observer collects data for a specified number been developed for these analyses—
of medications using preprinted forms. Figure 35-5
shows an example of an observation audit tool. Severity (impact on the patient’s health): Table 35-5 shows
2. The observer verifies each medication on the original a classification for determining the severity of ADRs. It
physician order in the patient chart, noting discrepan- addresses both ADEs associated with medication error
35.12 U SE

Figure 35-5 Nonvoluntary data collection tool for pharmacovigilance

Medication Administration Audit Tool

Date: Unit: Name of Evaluator:

Patient #1 Patient #2
Checklist for medication administration Met Not met Met Not met Comments
1. Washes hands before start of medication administration
process, before and after each patient contact, and
before preparing injectable medications.

2. Performs and charts necessary pre-administration

assessments for specific medicines (pulse, blood
pressure, nausea, etc.).

3. Notes allergies and compares to medicines to be

administered.

4. Correctly identifies patient. Compares name and/or ID#

on MAR with patient ID band. Cannot use room number
for identification.

5. Correct medication (removes medications and verifies

correct medication with the MAR).

6. Correct dosage (including accurate measurement of

liquids).

7. Correct route of administration.

8. Correct time of administration (administers within 1

hour before or after time ordered; considers relationship
to meals and/or food; waits appropriate time between
ophthalmic medicines, inhaled doses, etc.).
9. Explains purpose of each medication; answers questions
about the medication.

10. Stays with patient until each medication has been safely
swallowed.

11. Properly administers medications (preps IV port,

appropriate IV compatibility, administers over correct
time interval).

12. After medication administration, initials time of

administration for each medication and signs
appropriate document.

13. Correct disposal of pharmaceutical waste; disposes

of narcotics and dangerous drugs with applicable
documentation.

14. Maintains the security of the medications at all times

(locked medicine cabinet or locked medication room
door).

Source: Feinberg 2001.

MAR = medication administration record.
 35  /  Pharmacovigilance 35.13

Figure 35-6 Sample ADE/product quality problem form from Zambia

Zambia Pharmacovigilance Centre (ZPVC) in Lusaka

ADR Case Report Form
For adverse drug event and product quality problem reporting
In collaboration with the WHO International Drug Monitoring Programme
All information provided here will be treated as strictly confidential.
Client Information
Name (or initials): Age: Weight (kg):
Sex: M F LMNP   
/   
/    (if female) DOB:    /    /  Height (cm):

Adverse Event/Product Quality Problem

Adverse event (Form Part 1) And/or product quality problem (Form Part 2) Date of onset of reaction:     /    /   
Time of onset of reaction:     h     min
Description of reaction or problem (Include relevant tests/lab data, including dates):

1. MEDICINES/VACCINES/DEVICES (Include all medicines taken concomitantly.)

Trade Name and Batch No. Daily Date Date
(Asterisk Suspected Product) Dosage Route Started Stopped Reasons for Use

ADVERSE REACTION OUTCOME (Check all that apply.)

 Death  Life-threatening event Event reappeared on rechallenge: Recovered: Y N
 Disability  Hospitalization   Y  N  Rechallenge not done Sequelae:   Y  N
  Congenital anomaly  Other: Treatment (of reaction): Describe sequelae:
 Required intervention
to prevent permanent
impairment/damage
COMMENTS: (e.g., relevant history, allergies, previous exposure, baseline test results, laboratory data)

2. PRODUCT QUALITY PROBLEM

Trade Name Batch No. Dosage Form and Strength Expiry Date Size/Type of Container

Product available for evaluation?  Y  N

REPORTING DOCTOR/PHARMACIST:
Name Address

Telephone no.
Qualifications

Signature Date
This report does not constitute an admission that medical personnel or the product caused or contributed to the event.

Source: Zambia Pharmacovigilance Centre, Lusaka, Zambia.

DOB = date of birth; LMNP = last menstrual period.
35.14 U SE

Table 35-5 Severity index for medication errors

Category Description
Category A Circumstances or events that have the capacity to cause error (note that these are potential, not actual, errors).
Category B An error occurred but the error did not reach the patient (an “error of omission” does reach the patient).
Category C An error occurred that reached the patient but did not cause patient harm.
Category D An error occurred that reached the patient and required monitoring to confirm that it resulted in no harm to the patient
or required intervention to preclude harm.
Category E An event occurred that may have contributed to or resulted in temporary harm to the patient and required intervention.
Category F An event occurred that may have contributed to or resulted in temporary harm to the patient and required initial or
prolonged hospitalization.
Category G An event occurred that may have contributed to or resulted in permanent patient harm.
Category H An event occurred that required intervention necessary to sustain life.
Category I An event occurred that may have contributed to or resulted in the patient’s death.
Source: NCC MERP n.d.

and those not associated with error, so it can be applied

to all medication events. Box 35-2
Probable causality (likelihood that the medicine’s use or Determining whether a medication error
lack of use contributed to the ADR): Table 35-2 illustrates occurred
how to calculate the Naranjo Probability Score, a com- • Was the drug involved appropriate for the patient’s
mon method for determining whether a particular medi- clinical condition? (NO = Preventable)
cine was actually related to the ADR. • Was the dose, route, or frequency of administration
Preventability (Was an error associated with the event?): appropriate for the patient’s age, weight, or disease
Box 35-2 is an algorithm used to help determine if the state? (NO = Preventable)
ADE was caused by a medication prescribing error, and • Was required therapeutic pharmaceutical monitor-
therefore, preventable. ing or other necessary laboratory tests performed?
(NO = Preventable)
For ADEs that are considered preventable, identifying • Was there a history of allergy or previous events to
where the primary error occurred and what aspects contrib- the drug? (YES = Preventable)
uted to the system breakdown is useful; therefore, analysis • Was an interaction (medicine–medicine; medicine–
and reporting should facilitate this activity by identifying food; medicine–herbal) involved in the ADR? (YES
and targeting problem-prone areas, such as specific steps = Preventable)
in the process (prescribing practices), medication types • Was a toxic serum drug concentration (or laboratory
(injectables), disease states or patient types, employees monitoring test) documented? (YES = Preventable)
(new employees, interns), patient care areas (surgery), and • Was poor compliance involved in the ADR? (YES =
time of the day (night shift). For example, if data indicate Preventable)
that ADEs are caused by nurses giving the wrong dose of • Was the error considered preventable because of
injectable medications, then focused activities for improve- deviations in procedures or standards of practice?
ment should be developed. These activities might include (Yes = Preventable)
educational activities and procedural changes, such as
Source: Adapted from Schumock and Thornton 1992.
independent double-checks of all injectable medications.
After implementing the interventions, the error rate can be
checked for improvement.
Medication event data are organized on manual or elec-
tronic spreadsheets, which help summarize and sort data turer; the latter is especially important if the ADR has not
for reporting at the facility or regional level. National and been reported previously in the literature or is not included
international programs often use Internet-based ADR or on the product’s label. Reporting the results of ADR and
medication error databases to collect and share data. (See medical error analysis to the organizational body within
References and Further Readings.) a hospital or facility that has responsibility for medicine
ADRs should be reported to the national ADR program, safety, such as the drug and therapeutics committee, is also
if one exists, as well as to the pharmaceutical manufac- important.
 35  /  Pharmacovigilance 35.15

Country Study 35-1 shows how a research hospital in Most important at the clinical level, however, is taking
India established an ADR reporting system. action to improve medication safety and decrease medica-
tion events by developing a culture of safety in the health care
organization (see Box 35-3). For example, the organization’s
35.5 Taking actions for improvement leadership should maintain a clear commitment to safety
by emphasizing that safety takes priority over production
When ADEs occur, they must be analyzed and reported, and or efficiency; employee job descriptions and performance
their significance should be communicated effectively to an evaluations should include a component for participation in
audience that has the knowledge to interpret the informa- safety initiatives that are supported by recourses, rewards,
tion. National or even international actions that can result and incentives; and the response to a problem should focus
from the appropriate reporting of ADEs include— on improving system performance.
Country Study 35-2 illustrates the standard operating
• Pharmaceutical manufacturers sending out “Dear procedures and possible actions for addressing recur-
Doctor” letters to alert health care providers of newly ring ADRs in an ART program in Kenya. In a report on
discovered adverse reactions preventing medication errors, the Institute of Medicine
• Pharmaceutical manufacturers revising medicine (IOM 2006) urged that doctors, nurses, pharmacists,
package inserts that reflect the new information and other health care providers communicate more with
• Pharmaceutical manufacturers or national regulatory patients about the risks, contraindications, and possible
authorities instigating a medicine recall adverse reactions from medications and what to do if
they experience an ADE. In addition, patients should be
At the clinical level, actions concerning serious or encouraged to take a more active role in their own medi-
recurring ADEs include— cal care and should be given plenty of time to consult
with health care providers about their medications (see
• Changing the medication formulary if necessary also WHO’s patient safety initiative, http://www.who.int/
• Implementing new prescribing procedures patientsafety/en).
• Implementing new dispensing procedures In summary, the use of medicines involves a trade-off
• Modifying patient-monitoring procedures between benefits and potential for harm. Pharmacovigilance
• Educating professional staff (face-to-face; in-service can help minimize the harm by ensuring that medicines of
education; bulletins; reports of collected ADRs) good quality are used rationally and that the expectations
• Educating patients and concerns of the patient are taken into account when

Country Study 35-1

Implementing an ADR reporting system in India
ADR monitoring and reporting systems are uncommon Pharmacists may also report ADRs on their own. When
at the local level in developing countries. Although India the documentation is complete, the pharmacist analyzes
has a national ADR monitoring center in New Delhi, the causality, preventability, and severity of the ADRs
Kasturba Hospital, a 1,400-bed, tertiary care teaching using various scales, then issues the results quarterly.
hospital in Manipal had never had an ADR program Physicians who report ADRs may be given informa-
before 2001. It established an ADR monitoring center tion on how to manage the reaction, and if it involves an
not only to improve medication safety practices in the allergy, the pharmacist counsels the patient and provides
district, but also to provide a link between the region and an alert card for the patient to give his or her health care
the national center. The Kasturba Hospital program was provider. In the first year of the program, 142 ADRs were
launched and is maintained by the pharmacy depart- reported, including several rarely seen reactions, among
ment using established ADR-reporting centers in India them cisplatin-induced hiccups. As a result of the new
as models. program, the Kasturba Hospital staff saw an increase in
the awareness of the importance of ADR monitoring and
The Kasturba Hospital system relies on physicians and
reporting and improved interactions between the physi-
pharmacists working together. When a physician detects
cians and the pharmacists.
an ADR, he or she fills out the reporting form and sends
it to the pharmacy department, where a pharmacist fol- Source: Mohan, Rao, and Rao 2003.
lows up on the ward with an investigation of the incident.
35.16 U SE

Box 35-3
Safe medication practices
• Encourage staff to report ADRs, errors, and unsafe alternatives, use generic versus brand name or vice
conditions. versa to differentiate from sound-alike product).
• Change the safety culture from punitive to participa- • Label all medications in a standardized manner
tory. according to hospital policy.
• Standardize abbreviations, and develop a list of • Dispense medications labeled for a specific patient
dangerous abbreviations, acronyms, and symbols to and in the most ready-to-administer dosage form.
avoid. • Follow the five “rights” of drug administration: right
• Write or print clearly. patient, right drug, right time, right dose, and right
• Review medication orders for appropriateness before route.
dispensing and administration. • Verify patient identification against labels and orders
• Clarify medication orders that are not clear or do not prior to medication administration.
make sense for the patient’s clinical condition. • Develop a list of problem-prone or high-risk medica-
• Provide health care providers with access to drug tions and implement strategies to minimize the risk.
information. • Standardize or limit the number of drug concentra-
• Read back and receive confirmation on all verbal and tions available in the organization.
telephone orders. • Remove high-risk medications from patient care areas
• Identify look-alike and sound-alike products and take (for example, concentrated electrolytes).
action to avoid mix-ups (for example, physically sepa- • Involve patients in their care: tell them the name of
rate storage, clearly differentiate appearance, purchase the medicine and its purpose before administration.

health care providers are making decisions about therapy. Barker, K. N, E. A. Flynn, G. A. Pepper, D. W. Bates, and R. L. Mikeal.
WHO (2004) lists the best ways to achieve these goals— 2002. Medication Errors Observed in 36 Health Care Facilities.
Archives of Internal Medicine 162:1897–903.
Bates, D. W., D. J. Cullen, N. Laird, L. A. Petersen, S. D. Small, D.
• Serving public health and fostering a sense of trust Servi, G. Laffel, et al. 1995. Incidence of Adverse Drug Events and
among patients in the medicines they use that also Potential Adverse Drug Events: Implications for Prevention. JAMA
extends to confidence in the health service in general 274(1):29–34.
• Ensuring that risks in medicine use are anticipated and Classen, D. C., S. L. Pestotnik, R. S. Evans, J. F. Lloyd, and J. P. Burke.
managed 1997. Adverse Drug Events in Hospitalized Patients: Excess Length
of Stay, Extra Costs, and Attributable Mortality. JAMA 277(4):301–6.
• Providing regulators with the necessary information CPM/MSH (Center for Pharmaceutical Management/Management
to amend the recommendations on the use of medi- Sciences for Health). 2011. Center for Pharmaceutical Management:
cines Technical Frameworks, Approaches, and Results. Arlington, Va.:
• Improving communication between the health profes- CPM.
sionals and the public Dodoo, A. 2005. Safety Challenges of Preventing Malaria During
Pregnancy. WHO Drug Information 19(4):286–7.
• Educating health professionals to understand the effec-
Feinberg, J. L. 2001. Med Pass Survey: A Continuous Quality
tiveness and risk of medicines that they prescribe. n Improvement Approach. 2nd ed. Alexandria, Va.: American Society
of Consultant Pharmacists.
Ferner, R. E., and J. K. Aronson. 2006. Clarification of Terminology
References and further readings in Medication Errors—Definitions and Classification. Drug Safety
29(11):1011–22.
Flynn, E. A., K. N. Barker, G. A. Pepper, D. W. Bates, and R. L. Mikeal.
H = Key readings.
2002. Comparison of Methods for Detecting Medication Errors in
Ahmad, S. R. 2003. Adverse Drug Event Monitoring at the Food 36 Hospitals and Skilled-Nursing Facilities. American Journal of
and Drug Administration. Journal of General Internal Medicine Health-System Pharmacy 59(5):436–46.
18(1):57–60. ICTDR (International Centers for Tropical Disease Research
AHRQ (Agency for Healthcare Research and Quality). 2001. Making Network). 2003. ICTDR Investigator Manual: Monitoring and
Health Care Safer: A Critical Analysis of Patient Safety Practices. Reporting Adverse Events. Bethesda, Md.: U.S. National Institutes of
Rockville, Md.: AHRQ. <http://archive.ahrq.gov/clinic/ptsafety/> Health. <http://www.icssc.org/Documents/Resources/ICTDR_AE_
ASHP (American Society of Health-System Pharmacists). 1993. ASHP Manual_February_6_2003_final.pdf>
Guidelines on Preventing Medication Errors in Hospitals. American IOM (Institute of Medicine of the National Academies). 2000. To Err Is
Journal of Hospital Pharmacists 50:305–14. Human: Building a Safer Health System, L. T. Kohn, J. M. Corrigan,
 35  /  Pharmacovigilance 35.17

Country Study 35-2

Standard operating procedures for aggregating ADR data and taking appropriate action
in an ART program in Kenya
The Coast Provincial General Hospital in Mombasa, Suggested trends and actions for the data fields appear-
Kenya, was one of the first public facilities in the country ing on the ADR Summary Report and the ART ADR
to offer ART to AIDS patients. Hospital administrators Form appear in the following table. This table is not
and program managers realized the importance of moni- all inclusive; it merely provides a starting point for the
toring and reviewing ADRs related to the use of these ART Eligibility Committee, Scientific Committee, and
new, powerful antiretroviral medicines to ensure optimal Steering Committee to use when evaluating the ART
treatment outcomes and patient safety. The ART pro- ADR Reports.
gram staff designed and implemented standard operating
ADR actions on an aggregate level
procedures for ADR monitoring for all staff involved
Trends Possible actions
with the ART program.
An increase in • Notify the Scientific Committee.
All ART patients’ ADRs are reported on an ADR form. suspected or probable • Medicine may be used cautiously in
The forms are reviewed, compiled, examined for trends, ADRs associated with particular groups with extra patient
a specific age group, monitoring (lab or clinic visits)
and reported, and appropriate actions are taken in gender, pregnancy required.
response to the ADR report. Actions can be taken at the status, drug class, or • Medicine may not be given to
individual patient level or, in the case of a noted trend, at particular medicine particular groups.
the system level. A summary of the procedures for aggre- • Medicine may be removed from
gating the individual ADR data follows. treatment plan.
• ADR may be reported to the
Pharmacist in charge of the ART program— Pharmacy and Poisons Board by
the Steering Committee on the
1. Reviews the ART ADR Forms and ART ADR Reports recommendation of the Scientific
and prepares the ADR Summary Report at the end of Committee. Pharmacy and Poisons
Board may inform the manufacturer.
each month
• ART Eligibility Committee or
2. Looks for unusual trends Scientific Committee will investigate
3. Reviews the Actions Taken section of the reports possible causes of this increase
submitted to ensure that appropriate actions and take appropriate corrective or
preventive actions.
have been taken as decided by the ART Eligibility
Committee based on the outline in the following Serious ADRs associated • Notify the Scientific Committee.
with ADR probability • Medicine may be used cautiously
table category definite or with extra patient monitoring (lab or
4. Presents the ADR Summary Report to the ART probable clinic visits) required.
Eligibility Committee at the first meeting of each • not listed in the • Medicine may be removed from
month product labeling treatment plan.
or • ADR may be reported to the
5. Reports on unusual trends
• occurring in Pharmacy and Poisons Board by
6. Reports on inappropriate actions taken medicines less than the Steering Committee on the
five years since first recommendation of the Scientific
The ART Eligibility Committee— approved by the Committee. Pharmacy and Poisons
Pharmacy and Poisons Board may inform the manufacturer.
1. Reviews the ADR Summary Report and, if necessary, Board
the raw data
Appropriate actions not • Organize a training session.
2. Decides to take appropriate actions in response to being taken in response • Discuss with individual prescribers.
ADR Summary Reports or unusual trends or inap- to suspected ADRs as
propriate actions taken (possible actions are out- decided by the ART
Eligibility Committee
lined in the following table)
3. Forwards the ADR Summary Reports and presents Source: Standard Operating Procedures for ART Pharmacy, Coast Provincial
General Hospital, Mombasa, Kenya.
the findings to the Scientific Committee
The Scientific Committee reviews the ADR Summary
Report and decides on appropriate action to be taken.
35.18 U SE

a s s e s s ment g u ide

National activities Public health program activities

• Does the country address pharmacovigilance as part • Do the country’s public health programs (for
of its pharmaceutical legislation? example, HIV/AIDS, tuberculosis, malaria) have
• Do any national policies and practices exist that are their own ADR reporting systems? If so, what is the
related to pharmacovigilance? reporting structure?
• Who is responsible for overseeing national pharma- • Do the public health programs integrate their phar-
covigilance activities? macovigilance activities with national-level activi-
• Does a national pharmacovigilance center exist? If ties?
so, where is it housed?
Facility activities
• Does the national pharmacovigilance program
have a relationship with WHO’s Programme for • Does the facility track information on ADRs in
International Drug Monitoring? patients? Request an example of a recent report. Is
• Does a national ADR monitoring and reporting reporting passive (voluntary) or active (nonvolun-
system exist? If so, how many reports were submit- tary)?
ted during the previous year? What is done with the • Does the facility track medication errors?
reports? • What committee oversees the pharmacovigilance
• Is a system in place to report product quality prob- activities, and when did it last review a pharmaco-
lems? In the previous year, how many reports were vigilance report?
submitted on medicine product problems? • Does the facility have a culture of safety, that is, do
• Are reports of medical errors collected and analyzed employees feel comfortable reporting information
at the national level? on medication errors and ADRs? How many volun-
• Are the three areas—ADRs, product quality prob- tary reports did the facility have in the last year?
lems, and medication errors—combined in one • To whom are ADRs and medication errors reported?
reporting stream or separate streams? What is the mechanism?
• How is important information about ADRs commu- • Does the organization have an internal mechanism
nicated to health professionals? To the industry? To to analyze and address problems with medication
the media? To consumers? safety? Give examples of recent actions.
• Is pharmacovigilance included in university curri-
cula for health care professionals?

and M. S. Donaldson, eds. Washington, D.C.: National Academy E. Janecek, C. Domecq, and D. J. Greenblatt. 1981. A Method for
Press. <http://www.nap.edu/books/0309068371/html/> Evaluating the Probability of Adverse Drug Reactions. Clinical
IOM Committee on Identifying and Preventing Medication Errors. Pharmacology Therapeutics 30(2):239–45.
2006. Preventing Medication Errors, P. Aspden, J. A. Wolcott, J. L. NCC MERP (National Coordinating Council for Medication Error
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