WHITE PAPER
Literature Surveillance
Increasing Precision and Reducing Recall with Robust Strategies and Technology Platforms
Author
Andrew PurchaseDirector of Patient Safety OperationsPharmacovigilance & Patient Safety PRA Health Sciences
The author wishes to acknowledge the contributions of Senior Leadership from PRA Pharmacovigilance & Patient Safety (PVS).
White Paper | Literature Surveillance
Executive SummaryLiterature surveillance is an important tool in the suite of monitoring activities to ensure the safety of medicinal products. The
success of published literature surveillance is measured by precision and sensitivity. Pharmaceutical and biotech companies
must screen and analyze published literature from the clinical development stage, through post-marketing, as part of their
pharmacovigilance obligations. It is critical to detect safety signals as soon as possible to affect appropriate measures and
protect patient safety.
PRA Health Sciences has established consistent processes and clear accountabilities for literature surveillance to identify adverse
drug reactions, assess the expeditability of adverse reactions, review aggregate safety reports, and perform signal detection and
assessment. To ensure precision, PRA monitors global scientific and medical publications using large databases such as Medline
and Embase, as well as country-level journals.
An Introduction to Literature Surveillance During clinical development, it is mandated that drug
developers perform literature surveillance in accordance with
and in support of other surveillance activities, such as ongoing
safety evaluation or annual safety reporting (ie, Development
Safety Update Reports, or DSURs). This obligation intensifies
when the developer submits a New Drug Application (NDA)
or Marketing Authorization Application (MAA) and receives
authorization to market its product, as it then becomes a
requirement to perform a systematic literature review no less
than once a week. It is also expected that NDA and Marketing
Authorization Holders (MAHs) have procedures for monitoring
local publications in countries where the product has been
authorized for marketing.
Given the amount of available literature and the number of
potential sources (eg, Embase, Medline, Reactions Weekly,
Biosis), it is optimistic to expect to find every piece of literature
that may be published. Conducting a literature search requires
a realistic, pragmatic, and objective approach along with
targeted search strategies. These planning elements ensure
that the recall representing the number of results considered
relevant is as precise as possible.
Building a Robust Literature Surveillance Strategy It is essential that the development of the search strategy is
driven by the purpose of the search. Is the objective to look for
general safety information or Individual Case Safety Reports
(ICSRs), to identify new information about the medicinal
product, or to monitor a particular safety signal? In the clinical
development setting, exposure to the medicinal product
happens in a controlled environment and can be limited to a
certain patient population. When the medicinal product moves
to market, exposure widens to other patient populations, and
new or emerging safety information may be found. To build a
robust and targeted strategy, it is critical that it can evolve as
more is learned about the medicinal product and the objective
of the search changes.
Safety signals can arise from different sources of data,
including scientific literature. Scientific articles may describe
case reports with the use of a medicinal product or results
from studies conducted with the concerned product.
Monitoring the scientific literature can therefore provide
additional insight into the safety profile of a medicinal product.
When a safety signal is detected, the next step is to confirm
the causal association between the medicinal product and the
safety concern. This is achieved by looking at the strength of
the evidence, the clinical relevance, and previous awareness.
Reviewing scientific literature can help identify any similar
White Paper | Literature Surveillance
Figure 1:
safety concerns reported with the medicinal product in focus
or with products from the same pharmacological class. In
some circumstances, systematic literature reviews and meta-
analyses can be performed to further assess a safety signal
and support a more comprehensive analysis. In this scenario,
the research question should be clearly formulated, and the
selection of relevant publications, assessment of study quality,
summary, and interpretation of the findings should follow a
rigorous methodology.
Figure 1 offers a search strategy example to help visualize
how changes in the search strategy can impact the amount of
recall. Subsequently, Figure 2 provides insight into potential
time savings that can be realized.
Comparing Literature Recall
For this example, a search of PubMed was performed on
07 January 2021. The first search included the medical product
“Ibuprofen” and a publication date range of “01 January 2020
to 31 December 2020”. The second search included the
medical product “Ibuprofen” AND the event “Headache”
and a publication date range of “01 January 2020 to 31
December 2020”.
1200
0
200
400
600
800
1000
1016
19
Ibuprofen Ibuprofen AND Headache
Search Strategy (01Jan2020 to 21Dec2020)
Rec
all
In this example, you will note a 98% reduction in the amount
of recall when comparing the first and second searches.
Reducing the amount of recall may, in turn, increase the
precision, but some additional selection considerations
should be made.
Figure 2
Time Commitment/Recall
If we assume that each recall took an average of 4 minutes to
review, this figure represents the overall time commitment
to review the recall from the first and second searches
discussed in Figure 1.
Considerations to ensure recalls are not missed:
Databases: Consider which scientific databases and journals to search
Product terms: Think about factors such as alternative names, different spellings, and active substances of an indexed term
Search Terms: Consider the following search terms, which are often noted by regulators as being deficient in literature strategies:
• Outcome Terms (eg, Death)
• Pregnancy Terms (including uneventful pregnancies)
• Special Types of Reports (eg, Asymptomatic Overdose, Medication Errors, Misuse, Abuse, Occupational Exposure)
Time to Review
First Search = 68 hours
Second Search=1.3 hours
White Paper | Literature Surveillance
Automation of Literature Surveillance Despite the best efforts and most sophisticated strategies,
the amount of literature recalled can still be overwhelming,
particularly for companies with hundreds of products in
development and on the market. This is one of many similar
instances where technology and automation offer a solution.
Robust platforms can significantly reduce effort and improve
efficiency for literature surveillance activities. Technology
facilitates standardized, automated workflows that maximize
literature operations and provides a single platform/repository
for storing surveillance data. When searching multiple data
sources, such technology also performs de-duplication by
flagging duplicate results and highlights keywords to expedite
literature reviews and shorten the time for locating relevant
information. It is well documented that the deployment of
such literature platforms can reduce review times by 20-40%,
as shown in Figure 3.
The Impact of Automation
If we refer back to Figure 2, where we presented the time
commitment/recall, we can conclude that the literature
platform can reduce the review time by up to 40%.
Time to Review:First Search
Without Literature Platform= 68 hours
With Literature Platform= 32.8 hours
Time to Review:Second Search
Without Literature Platform= 1.3 hours
With Literature Platform= 0.78 hours
Implementation of these platforms streamlines oversight and
coordination of literature surveillance activities and ensures
inspection readiness. Such systems also enable ongoing
monitoring of the performance of the process and literature
strategy by providing access to on-demand reports.
Figure 3
PRA's Standalone Literature Surveillance Platform Features Include:
Detection and Removal of Duplicates (ie, De-Duplication)
Creation of Standardized Review Workflows
Keyword Highlighting
Reference and User Permissions Management
Central Storage of Articles
Creation of On-Demand Reports for Key Performance Indicators
Literature Surveillance of VaccinesOnce a new medicinal product is approved, a certain level of
scrutiny to the product’s safety should always be expected.
A public health emergency such as the COVID-19 pandemic
calls for a global effort to develop safe and effective treatments/
vaccines to combat the disease. While the timeframe for the
development of such treatments/vaccines may be shorter, there
can be no compromise in patient safety. That being said, the
shortened timeframes can increase the level of scrutiny that
these treatments/vaccines may face. Of course, routine
literature surveillance is a mandated requirement for a newly
approved medicinal product; however, we should be prepared
for a significant increase in the amount of recall when performing
literature surveillance during a public health emergency.
If we continue with the example of COVID-19, the development
of a robust literature strategy is more critical than ever. As part
of the literature strategy, it might be important to consider, for
example, the development of the vaccines, the evolution of the
disease, and the available treatment options. In addition, since
the landscape of such public health emergencies is constantly
White Paper | Literature Surveillance
PRA and Literature Surveillance PRA has the resources, processes, and technologies to support
effective literature surveillance. Our team of experienced
information specialists has backgrounds in the medical,
healthcare, scientific, and information technology industries.
PRA employs subject matter experts (SMEs) to manage
literature surveillance, as detailed in Figure 4.
evolving, it is essential to continually monitor the effectiveness
of the literature strategy and revise it with increased frequency.
Otherwise, it might be expected to recall between 500 to 1000
results per day.
When performing literature surveillance under an increased
level of scrutiny and with a likelihood for a high volume of
information, having a literature platform is more important
than ever.
PRA is a leader in all aspects of literature surveillance for
pharmaceutical and biotech companies, both in the clinical
development and post-approval environments.
Library Technicians• Develop, validate, and revise literature strategies
Drug Safety Associates (DSAs)• Execute searches, review abstracts, and procure selected articles
Safety Scientists
• Provide oversight of the process, review abstracts and articles
Safety Physicians
• Assess articles and summarize the review results
Qualified Person for Pharmacovigilance (QPPV)/Local Person of Pharmacovigilance (LPPV)
• May also be involved in the review of the search results (ie, in a post-approval environment)
Pharmacoepidemiologists
• Support with systematic literature reviews and meta-analysis
Figure 4
PRA supports the following type of literature surveillance activities:
Routine Pharmacovigilance
Aggregate Safety Analysis (DSUR, Risk Management, Signal Detection)
Adhoc Literature Reviews (support of Adhoc Signal Detection)
Local Literature Surveillance
Systematic Literature Reviews and Meta-Analysis (Real World Information)
White Paper | Literature Surveillance
References1. https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/guideline-good-pharmacovigi-
lance-practices-gvp-module-vi-collection-management-submission-reports_en.pdf
PRA Health Sciences conducts comprehensive Phase I-IV biopharmaceutical drug development. To learn more about our solutions, please visit us at prahs.com or email us at [email protected].
White Paper | Literature Surveillance
Contact Information
For further information regarding PRA’s approach to literature surveillance or to discuss any aspect of PRA’s services, please contact your PRA account director or the PRA employee below:
Andrew Purchase
Director, Patient Safety Operations
Pharmacovigilance & Patient Safety
Phone: +44 (0) 1792 525 623
World Headquarters
4130 ParkLake Avenue, Suite 400
Raleigh, North Carolina 27612 USA
Phone: +1 (919) 786 8200
Fax: +1 (919) 786 8201
www.prahs.com
MA
R 2021
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