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360 Cobert’s Manual of Drug Safety and Pharmacovigilance
cases (7- and 15-day cases) whether by paper or E2B.
Whether copies of submissions should be exchanged
(even though the electronic file or identical MedWatch
or CIOMS I form has already been exchanged by the
drug safety groups) should be stated. This might be
necessary if the other party wishes to know the serial
number (in IND submissions) or date of submission.
Roles and responsibilities for EudraVigilance submis-
sions should also be clarified. If MedWatch or CIOMS
I forms are used for exchange, provision must be made
to database those reports that must be rolled into aggre-
gate tables for submission to regulators (or to respond
to queries, etc.).
Similarly, all other regulatory submissions (investi-
gator brochures, labeling changes, PSURs/PBRERs, NDA
periodic reports, annual reports, IND annual reports,
information amendments, desk copies, post-marketing
commitments, REMS/RMPs, etc.) should be spelled out
and exchange methodology noted. It is critical to spec-
ify whether the other parties have review and approval
privileges or are merely given information copies of
such documents.
Investigator and
Investigational Review
Board/Ethics Committee
Notifications: Blinding and
Unblinding, Data Monitoring
Committees (DMCs/DMSBs/
DMSCs), Data Safety Boards
The mechanism and responsibilities for the prepara-
tion of the investigator notification of expedited reports
(also called the investigator letter), new IB versions, and
changes in the benefit–risk analysis need to be detailed.
In addition, in those countries where the sponsor must
inform the Ethics Committees/Investigational Review
Boards, this should be spelled out. It should be clarified
whether the same exact letter is to be used worldwide,
and if so, whether a mechanism for its preparation
(within the same 15-calendar daytime frame required
for the alert report) must be specified. The language is
usually English, but any requirements for translations
must be noted and responsibility specified.
Most regulatory agencies prefer or require that all
expedited reports be submitted unblinded (the code
broken). If this is done, the companies must agree on
a mechanism for unblinding and the transmission of
the unblinded cases (or just the unblinding code) to the
other party(ies). This can be challenging if companies
want to keep the clinical research team and statisticians
blinded.
If one or more Data Safety Management Boards
(DSBs/DSMBs)/Data Monitoring Committees (DMCs)
are involved either in clinical trials or even (as some
companies now do) after marketing, the responsibilities
of the partners in regard to these committees should be
spelled out, including the powers and functions of the
boards and the interactions with the various partners.
Similarly, if a DSB/DSMB is created (per FDA guid-
ance or other HA recommendation) to oversee the whole
project and all the protocols, the membership, duties,
and functioning must be specified. Safety Assessment
Committees (SACs), if they exist, must also be agreed
upon.
Safety Databases
The parties should agree on who will keep and main-
tain what data in their respective databases. It should
be agreed by all parties that one party (often the largest
company; the originating company, or the party with
the more robust pharmacovigilance function) maintains
the “official” database that will be used as the definitive
one for preparing all regulatory reports.
It is nearly impossible, if not totally impossible, to
maintain up-to-date, fully reconciled databases when
each party has its own database. The maintenance of
reconciled, separate databases by each company (even
if the same brand of commercial database) produces
differences between or among the databases. Problems
arise if there are different drug dictionaries, different
ways of handling data (e.g., laboratory), different cod-
ing conventions, different MedDRA versions, different
narrative writing styles, and so on. Mechanisms exist
where outside parties may have limited access to the
Business Partners and Exchange of Safety Data 361
official database though the database owner often hes-
itates to allow this. Also, duplicative databases add to
the cost structure.
If agreement cannot be reached on allowing one
partner to maintain the official database, all parties
should “agree to disagree” and accept that each will
maintain a database but that one agreed-on database
will be the “official” one for regulatory reporting and
audits/inspections. In the European Union, the EU
Qualified Person for Pharmacovigilance must be phys-
ically present in an EU member state with direct access
to the database, making this database the “official” one
for the European Union at the very least. The database
is supposed to also be situated in the country where
the EU QPPV is located. However, this requirement was
created when databases remained on individual, physi-
cal servers. Now with cloud computing, this point is, to
a degree, moot but it is still in place. In any case, the EU
QPPV needs immediate access to the data even if access
is via an intermediate person (often a technical person).
As an alternative, only one database is maintained
by one company with access to the data for the drug in
question by the other companies. This has been prob-
lematic in the past but newer technologies, with the data-
base located in the “Cloud”, can go a long way to resolve
this if all parties agree. The major difficulties are usually
political and corporate rather than technical or IT.
The parties must agree on whose SOPs, guide-
lines, manuals, and so forth, apply where, when, and
to whom. In some cases, one or more new SOPs will be
created for that partnership only. In other cases, each
party uses its own SOPs and reconciliations or changes
are made as needed.
Definitions
Either in the body of the agreement or as an appendix,
the parties should agree on the definitions of terms used,
including serious, non-serious, medically significant
(important), labeling, expedited, expected, unexpected,
labeled, unlabeled, listed, unlisted, and causality (relat-
edness) in clinical trial cases. This may be a contentious
issue because there are no international standards for
causality, and the parties need to agree on definitions,
particularly for ambiguous terms such as unlikely
related, the four criteria for the minimal dataset, clock
start date, and so on. The language of exchange should
be specified as well, and how documents not in English
will be handled (full translations or not, certified or
not). It is quite challenging to agree on text to describe
medical judgement.
The clock start date is sometimes an area of con-
troversy. The United States and the European Union
largely agree that the clock start day is day zero and it
starts when anyone anywhere in any company, agent,
distributor, and so forth, receives sufficient detail to
make the case a valid ICSR (patient, drug, reporter, AE).
Not all countries agree on this, however, and some start
the clock at a later date (when the case is received by
the company in that country from a foreign source). The
most conservative and usually wisest course is to start
the clock when the first person anywhere has enough
detail for the case to be valid.
Data and Mechanisms
of Data Exchange
The physical exchange method must be specified as
follows:
Paper copies versus E2B;
“Push versus pull”, that is, does party A send
(“push”) data to party B or does party B go onto
a website or portal to obtain (“pull”) it. How are
confirmations handled? It is not enough for party
A to send a case; party B must actually receive it.
This needs to be verified with acknowledgment of
receipt mechanism built in, i.e., automatic;
Mechanism of transmission: e-mail with attached
PDF files, etc., source documents; in some excep-
tional situations faxing is still done;
Documents in which a signature copy (hand-signed
or electronic signature) is needed to be maintained
on file;
Privacy and anonymization issues to ensure data
security and privacy.
Documents to be exchanged must be specified.
This is particularly critical for individual case reports.
362 Cobert’s Manual of Drug Safety and Pharmacovigilance
Will an E2B file be exchanged or will the exchange
media be MedWatch forms, CIOMS I forms, an SAE
data collection form, or source documents? If CIOMS
I or MedWatch forms are exchanged, will they be com-
plete or in draft and on what day after clock start? Will
all review be done by partners electronically in the
database? If source documents are exchanged initially,
will finalized MedWatch or CIOMS I forms or final
electronic case files also be exchanged? Is it acceptable
that each party creates its own narrative and coding,
realizing that there will be differences between the two
(or more) parties? If reconciliation is desired, how
can this be done rapidly so that 7- and 15-day reports
are consistent? How are follow-up data requested and
handled?
1. In practice, it is common for the party that
receives the case to handle the full processing of
the case (including follow-up). A completed E2B
file (or other agreed medium) is sent to the other
partner(s) by a particular calendar day (often 3–4
days after clock start). This will allow the other
parties to upload or enter the data into their data-
base (unchanged) and transmit any expedited
cases to the health authority, per their obliga-
tions under the PVA. This will also allow them
time to check the case against local labeling if the
product is marketed with different labeling in the
recipient company’s territories.
2. Once a sufficient volume of cases is attained (sug-
gesting success in the clinical trial or marketing),
a “well-oiled machine” must exist to process and
transmit SAEs, particularly if the volumes are
high. Reconciliation and “discussions” over par-
ticular cases must be the exception and not the
rule if on-time regulatory reporting is to be main-
tained. Keep in mind that submission of a case as
an expedited report does not admit that the drug
caused the event.
3. Seven-day expedited reports from clinical tri-
als must be handled in a much more rapid time
frame (usually 2–3 calendar days) to ensure reg-
ulatory compliance.
4. Companies should reach agreement that the most
conservative call on seriousness, expectedness,
and causality carries the day for SAEs. That is,
if one company believes a case is unlabeled or
possibly related and the other does not, the case
is considered unlabeled or possibly related. This
may force a company to submit a case as an expe-
dited report that it does not believe to be one
because the other company does. If this is the
case, management should be made aware of this
to avoid possible issues down the road. A mech-
anism for timely dispute resolution (or default)
should be specified.
5. If CROs are involved, the agreement must
account for them in terms of timing and exchange
method. Written agreements with the CROs are,
of course, required. The regulatory agencies must
be notified in writing of the duties devolved onto
the clinical research organization(s).
Note that working with multiple CROs (e.g.,
one or more on each continent or one of the CROs
is the “lead CRO”) can be very tricky as many of
them are competitors. There may be difficulties
in getting such competitors to work together to
exchange cases, share and review SOPs, etc.
6. In the European Union, if there are several com-
panies and thus, several EU QPPVs, the single
“designated” QPPV should be noted and the
dealings between and among the other QPPVs
clarified. Similar relationships in other territories
that require local responsible persons should,
likewise, be clarified.
7. Follow-ups are done by the party receiving the
original SAE (or non-serious AE if follow-ups are
done for these). The other parties may pose ques-
tions for the company doing the follow-up but
usually follow-up is left to their discretion and
medical expertise. It should be specified when it
is done and how frequently.
All follow-up information is handled in the same
manner as initial information. It should be stated
clearly who reviews the worldwide literature for SAEs
and NSAEs and how they are handled when found.
If the drug is marketed in the European Union, lit-
erature for the product should be searched weekly.
This includes accessing EMA’s Medical Literature
Business Partners and Exchange of Safety Data 363
Monitoring database for relevant case reports from
the literature. In addition, MAHs with EU MAs must
search the EudraVigilance database and perform signal
detection.
A method used by many companies is as follows:
All SAEs are exchanged as E2B files (or CIOMS I/
MedWatch forms) by calendar day 10 at the lat-
est after clock start anywhere in the world at the
first company (or agent) and used as-is, without
changes to coding or narrative. Much less com-
monly, the SAE data collection form or source doc-
uments (from clinical trials and spontaneous cases)
are exchanged by calendar day 5. In this case, each
company writes its own narrative and does its own
coding based on this “source document” to create
an ICSR. Each company submits its own version to
the regulatory agencies in its domain. Because these
reports are created by each company on their own,
they differ and will require reconciliation or default
for signaling and aggregate reporting. If some docu-
ments are not in English, this should be noted and
should not be a surprise to the company receiving
untranslated documents.
All clinical trial deaths or life-threatening SAEs are
exchanged within 3 or 4 calendar days. Sometimes
this is limited to the subset of unlabeled (unex-
pected) cases only; this requires that the receiving
company trust the judgment of the sending com-
pany on labeledness. This covers 7-day expedited
cases.
All non-serious spontaneous cases are exchanged
on a monthly basis (or twice monthly if the volume
is very large). Computerized line listings or E2B
files (or MedWatch/CIOMS I forms) may be used.
Non-serious clinical trial cases are not exchanged
and are kept only in the clinical trial database of
the company(ies) doing the trial. Non-serious cases
must be periodically reviewed for seriousness (or
adverse events of special interest) to ensure all seri-
ous cases are identified.
Follow-up is done for all SAEs, with at least two
contacts attempted for spontaneous cases (more if
a critical case such as an alert report) and whatever
is necessary for clinical trial cases (the investigator
should be accessible to give complete follow-up).
Signaling, Safety Reviews,
and Risk Management
The agreement should specify how signaling is done
by one or more parties and, if so, how disputes are
resolved. It is common to form a safety review commit-
tee that meets periodically, usually by telephone, webi-
nar, or video conference, to review the logistics and
operational issues of safety handling as well as any SAEs
and safety signals that arise. All signals must be tracked
to resolution.
Usually, the logistics and operations dominate the
initial meetings until all glitches are resolved. At that
point, with operational issues minimal and with more
SAEs arriving, the signal reviewers predominate. Meet-
ings may be weekly to biweekly initially and then at a
monthly or quarterly frequency if no safety or signal-
ing issues arrive. Ad hoc meetings should be held, as
needed, for urgent issues. It should be clear how risk
management is handled and who prepares and approves
any RMPs or REMS that might be needed.
Note: A Partnership Management process must be
implemented. As specified above, it could be part of the
periodic exchanges about signal and risk management.
Nevertheless, each party must have active and ongoing
oversight of the exchanges and be able to identify any
deviation from the contracted agreement in order to
alert the partner, if needed.
Audits
A quality system procedure should be in place to ensure
that all requirements for safety are in place. Audits of
each partner should occur periodically to ensure this.
The audits may be done by each company (or a third
party) and should look at the contracts to be sure they
are adequate and that their provisions are followed by
the responsible parties.
364 Cobert’s Manual of Drug Safety and Pharmacovigilance
Other Issues
If not noted elsewhere, mechanisms for dispute resolu-
tion should be described in detail.
Other product-specific issues relating to devices,
vaccines, biologics, and nutraceuticals;
Any specific regulatory requests (e.g., special report-
ing of certain SAEs or reporting of adverse events of
special interest) should be mentioned;
An agreed-on time to review the safety exchange
agreement should be specified. It is usually yearly
but may be more or less frequently if circumstances
warrant. Any change in regulatory status (e.g., a
new trial, indication, MA/NDA approval) or new
safety regulations should trigger a review of the
safety agreement;
Agreement on who does medical literature searches,
including responsibility for searching the EudraV-
igilance Medical Literature Monitoring service,
should also be noted;
Risk management agreements and post-marketing
commitments/requirements with health agencies
should also be exchanged and agreed on;
Risk management/minimization issues (including
measuring effectiveness of any non-routine inter-
ventions) and post-marketing commitments and
promises;
Inspections and audits of one another and by third
parties (that is, health agencies). How are they han-
dled? Who is present? How are issues resolved?;
All arrangements must be written down in the Phar-
macovigilance System Master File (PSMF) kept by
companies with MAAs or MAs in the European
Union and in other territories where required;
Duplicate submissions of cases to the same health
authority must be avoided (Who runs duplicate
detection?);
A mechanism to track changes in safety regulations
and requirements should be in place and the agree-
ments updated as needed;
Usual and unusual marketing arrangements and
programs must be covered (e.g., patient support
programs, local clinical or observational trials);
If companies merge, acquire, or sell or transfer the
MA, the safety responsibilities must still be done
and accounted for;
Any outsourcing or sub-contracting (if permitted)
should be agreed by all parties;
Training, particularly where differences in proce-
dures produce different processes, must be done,
coordinated, and documented, as necessary;
A mechanism to handle crisis management, recalls,
withdrawals, and stopping trials must be developed
and agreed on;
Appendices.
The appendices should contain information that
may change frequently, including names, addresses,
contact information, territories in question, product
names, and registration numbers.
Soft Points
Do not underestimate cultural (both national and
corporate) differences, language matters, business
etiquette, communication, leadership, and logistics.
Someone must be in charge and the maximum in
diplomacy and goodwill should be used to smooth
and resolve the issues that will inevitably arise.
Keep in mind time zones when partners are on two
or more continents. If Asia, North America, and
Europe are involved, someone will always be up in
the middle of the night for any teleconference! Also,
consider differences in national holidays; definition
of “weekend” in the US and Saudi Arabia falls on
different days of the week.
Particular difficulties may occur in “big pharma” —
“small pharma” agreements. The “big” players
should be particularly sensitive not to dictate a
“know-it-all” attitude. There must be understand-
ing that some things will be difficult politically and
culturally in the other company because of politics,
culture, stubbornness, and local legal matters. Small
companies may not have the resources of big play-
ers and one person may have many responsibilities.
It is wise to have at least one face-to-face meeting
before the contract is in place and then periodically
after the contract begins.
Not everybody speaks, writes, or understands
English well. This is particularly an issue between a
large company located in a native-English-speaking
country and a small firm in a non-English-speaking
Business Partners and Exchange of Safety Data 365
country. Not everybody realizes they don’t speak or
understand English well. Again, sensitivity to such
differences should be kept in mind.
Management should be (where possible) sensi-
tized to the criticality of safety data exchange. Fail-
ure to get this right can produce enormously bad
consequences for all parties (not to mention the
patients!).
Comments
Health authorities and inspectors are now paying par-
ticular attention to Pharmacovigilance Agreements
(PVAs) as more complexity has been introduced into
the pharmaceutical world, with more outsourcing, frag-
mentation, and specialization of functions.
Inspectors insist that all responsibilities be noted in
contracts and agreements so that all PV obligations are
fulfilled. In the European Union, the EU QPPV or dele-
gate will be the focal point for this. The inspectors will
expect the contracts and documents to be available and
the appropriate parts to be in English so that they (and
the drug safety department) can evaluate them. Since
PVAs can be signed by partners from different countries
(or states in the US), it may be useful to specify accord-
ing to which law they will refer in case of dispute.
Drug Due Diligence
Before buying or licensing in a medicinal product, an
assessment of its dossier should be conducted. A ded-
icated team can be set up to run this Due Diligence
(DD). Usually, the following stakeholders are involved:
Non-clinical, Clinical, Marketing, Legal, Medical, Reg-
ulatory, PV, and manufacturing.
The purpose is to conduct a deep analysis on all
available data and then deliver a synthesis report for the
Senior Management, which will then take the decision
to buy (or not to buy) the product.
For PV data, the challenge is to identify two kinds
of difficulties or weaknesses: PV System Robustness
and Drug benefit–risk profile, as shown in the follow-
ing table.
For each item, a deep analysis is to be conducted.
Therefore, the DD is usually managed on site in the
other company, a list of all needed documents is to
be provided to the counterpart at least several days
before the face to face DD; each requested document
must be provided.
As regards PV System robustness, it is key to iden-
tify strengths and weaknesses for each specified item;
e.g.: if we identify that the PV team did not manage
ICSRs according to the currently accepted standards,
this could explain the perhaps overly positive safety
profile delivered at the end of the clinical develop-
ment. On the other hand, if the PV System is assessed
as robust enough, it would mean that one can trust
the provided safety data. When running the DD for
PV, it is also important to check whether any critical
changes have impacted the partner organization during
the clinical development program; we can imagine for
instance that a PV System is robust for two years, but
had been weak over the previous years during clinical
development.
The second level of assessment is linked to the drug
safety profile and then to the benefit-risk balance. This
is more classical for PV employees but must be delivered
after a careful analysis. In the DD report, PV must actu-
ally provide the company’s senior management with a
PV assessment as well as with proposals if the collected
data are raising doubts or unanswered questions. If it is
Table 1
Example of Categories of Potential
Pharmacovigilance Challenges
The PV System Robustness The Product Safety
Assessment
Quality Assurance system (including
previous CAPAs or Inspection
findings)
Drug Class Safety profile
Case Management processes Identified Risks
Regulatory Compliance Potential Risks
IT System Missing Information
Partnerships/SDEA Risk Management Plan
Signal Detection Process Safety Surveillance during
Clin. Devt
Risk Management System Benefit/Risk Balance
Pharmaco-Epidemiology
PV Organization
PV Members Education & Training
366 Cobert’s Manual of Drug Safety and Pharmacovigilance
key to assess the available data, it is also key to identify
the important missing data, if any.
Even if many stakeholders are involved in the DD
process, the PV conclusions are those which can break
the deal. The DD PV report must be very clear in the
conclusion with a “Yes” or a “No”, sometimes specify-
ing reservations leading to a “conditional Yes”; having
to face to a significant safety issue soon after contract
signature can be very challenging if not anticipated in
the DD conclusions.
Sometimes, alas, safety issues can be buried or
coded to minimize or even hide them. The authors have
seen this unfortunately. In general, trust but verify.
Finally, beware if one or more of the partners
want the DD analysis to be delivered orally and not in
writing. The assessment should always be documented
in writing.
CHAPTER
367
33
Where Data Reside
S
afety data can come from a variety
of sources; limited sources during
clinical development, expansive
sources after market. Much of it is reli-
able and verified (for example from
tightly controlled clinical trials), but
much is not. The challenge is obtaining
the necessary and relevant data, veri-
fying that it is valid and correct, ensur-
ing that no duplicates occur, getting it
into a database accurately, and making
valid clinical judgments at the individ-
ual patient level and at the aggregate
(public health) level. Since data con-
tinue to accumulate over time, as with
everything else in drug safety, this is a
moving target. This chapter will focus
mainly on external sources of safety
related data.
Introduction
Adverse event (AE) data are collected all over the world
by many people and groups. There is little standardiza-
tion in the way they are collected, how they are mea-
sured and graded, how they are stored, and how they
are used. Some of the data are collected as a matter of
public health, and some are collected by pharmaceu-
tical companies, other companies, non-governmental
organizations (NGOs), or patient advocacy groups that
process the data and make them available or sell them
to others. In theory, with the International Council for
Harmonization (ICH), the Council for International
Organizations of Medical Sciences (CIOMS), the Med-
ical Dictionary for Regulatory Activities (MedDRA
®
),
and work products of other Standards Development
Organizations, such as ISO, HL-7, and CDISC, the PV
368 Cobert’s Manual of Drug Safety and Pharmacovigilance
world is moving toward improved standardization and
use of these data.
AE data reside in several places. One main resource
is the US Food and Drug Administration (FDA).
FDA Adverse Event
Reporting System
The FDA has a large amount of data stored in four pub-
licly accessible databases of primarily post-marketing
safety data, as well as other proprietary databases con-
taining clinical trial information. The FDA database for
all approved drug and therapeutic biologic products,
the FDA Adverse Event Reporting System (FAERS), is
discussed here.
FAERS (www.fda.gov), like its predecessor, FDA’s
Adverse Event Reporting System (AERS), is a reposi-
tory for information about AEs, medication errors, and
product problems on marketed drug and therapeutic
biologic products. It is ICH E2B compliant and Med-
DRA
®
is used for coding.
The FAERS database contains the following:
Voluntary reports from healthcare professionals and
consumers submitted directly to FDA through the
MedWatch program;
Reports from manufacturers required by regulation,
stratified as:
Expedited reports, which have at least one SAE
that is not in the Package Insert;
Non-expedited reports, all reports that do not
meet the criteria for expedited reports;
Biological Safety Reports (BSRs), which are a unique
type of 15-day reports submitted to FDA until 2005.
AEs for human cells, tissues, and cellular and tis-
sue-based products (also known as HCT/Ps) and blood
and blood components are also included in FAERS but
are only available through a Freedom of Information
(FOI) request (see below).
FDA uses FAERS data to look for new safety con-
cerns, evaluate regulatory compliance of manufactur-
ers, and respond to outside requests for information.
If a potential safety concern is discovered, further eval-
uation is performed. This might involve conducting
additional studies, e.g., querying Sentinel data. (FDA’s
Sentinel System does not actually have a single database,
but, rather, is able to query a network of anonymized
electronic health records.)
Based on an evaluation of available data and the
concern, FDA may take regulatory action(s), such as
updating a product’s labeling information, restricting
the use of the drug, communicating new safety informa-
tion to healthcare providers and the public, or, in rare
cases, removing a product from the market. Of course,
in some instances no action is needed.
FAERS data are available to the public in these ways:
FAERS Public Dashboard which is an interactive
web-based tool that supports queries;
FAERS Quarterly Data Files which has raw data
extracts that can be downloaded (searches require
familiarity with relational databases); Redacted
ICSRs, which can be obtained through Freedom of
Information (FOI) requests to FDA https://www.
fda.gov/regulatoryinformation/foi/default.htm.
FAERS Public Dashboard
Direct search capability is provided to the public by the
FAERS Public Dashboard). The reports in FAERS should
not be considered complete and should be interpreted
with caution. FDA includes a lengthy disclaimer with
the FAERS Public Dashboard. The following is an extract
of the disclaimer: “Although these reports are a valuable
source of information, this surveillance system has lim-
itations, including the potential submission of incom-
plete, inaccurate, untimely, unverified information. In
addition, the incidence or prevalence of an event cannot
be determined from this reporting system alone due to
potential under-reporting of events and lack of infor-
mation about frequency of use. Because of this, FAERS
data comprise only one part of the FDA’s important post-
market surveillance data and the information on this
website does not confirm a causal relationship between
the drug product and the reported adverse event(s).”
The Public Dashboard is designed to facilitate easy
data queries by the public. Data can be displayed in chart
Where Data Reside 369
format. For example, users can view a summary of AE
reports received from 1968 to the most recent quarter
for which data are available or for a specific timeframe.
Users can also search on a specific product within a spe-
cific timeframe and sort by simple demographics. Data
updates are made periodically.
Data fields available through the FAERS Public
Dashboard are a subset of the data fields available in the
FAERS Quarterly Data files. This is subject to change
over time. Also, FAERS Public Dashboard data may not
be identical to the corresponding data in the FAERS
Quarterly Data files due to different data extraction dates.
The data may be downloaded into Excel spreadsheets.
FAERS Quarterly Data Files
Quarterly (non-cumulative) data files since January
2004 are available for downloading. Data include infor-
mation on patient demographics, the drug(s) reported,
the adverse reaction(s), patient outcome, and the source
of the reports. The actual files can be downloaded
directly. The data can be manipulated (though not eas-
ily), and various companies offer services that include
periodic updates, data searches, or repackaging of the
data in a more user-friendly form. The database cannot
be searched directly.
There is a variable lag of several months between
AEs being reported to the FDA and their making it into
the quarterly data files. Should further information
be desired after reviewing the data from the quarterly
report, the full MedWatch form (anonymized to pro-
tect the reporter and patient) can be obtained using the
unique identification number assigned to each case by
the FDA.
Redacted ICSRs
Individual FAERS reports, with personal identifiers
redacted, may be requested via the Freedom of Infor-
mation (FOI) process.
There are private companies that, for a fee, will
make the requests anonymously and some companies
use these services to obtain information on their com-
petitors’ products while remaining anonymous. An FOI
request can be made online. Although getting and using
the data can be difficult, it can be rewarding because
large amounts of detailed data are available, particularly
for newer products. The full MedWatch forms are avail-
able, redacted, and the narratives can be read to obtain
clinical summaries of the cases.
Clinical Trial Data
There are few clinical trial data in the FAERS database.
(These are reports for products with an approved NDA
that are also being used in an investigational trial under
an IND.) The clinical trial data are proprietary and are
generally not available, although some advocacy groups
would like to see a change in this. The clinical trials
registry housed by the National Cancer Institute (NCI)
will hold more data (including more safety informa-
tion) in the next few years as increased compliance with
legislative requirements evolves. In early 2018, FDA
announced that it is starting a pilot project with the
voluntary assistance of several pharmaceutical compa-
nies to release some heretofore proprietary data. If this
succeeds, expect more data to become available from
clinical trials.
Some clinical trial safety data can be found in Sum-
mary Basis of Approval documents that the FDA releases
when a drug is approved. They are not easily found on
the website and need to be searched for using the search
box. There are certain cooperative efforts to consolidate
clinical trial data, safety and efficacy, for trusted third
party guardianship and anonymization so data can be
re-purposed for research use. For example, Project Data
Sphere (www.projectdatasphere.com), an independent,
not-for-profit initiative operates a platform, essentially
a free digital library-laboratory that provides one place
where the research community can broadly share, inte-
grate and analyze historical, patient-level data from a
broad cooperative of academic and industry phase III
cancer clinical trials.
Post-market Requirements and Commit-
ments may be searched for at https://www.fda.gov/
drugs/guidancecomplianceregulatoryinformation/
post-marketingphaseivcommitments/.
Potential Signals of Serious Risks/New Safety Infor-
mation that FDA has found in FAERS is available at