Department of Health and Human Services

OFFICE OF

INSPECTOR GENERAL

HOSPITAL REPORTING

OF ADVERSE DRUG REACTIONS

V.RVICES. 
Richard P. Kusserow 
INSPECTOR GENERAL 
'0 
mL Y 1991 
lj  \'dla  OFFICE OF INSPECTOR GENERAL

The mission of the Office of Inspector Oeneral (010), as mandated by Public Law 95-452, as 
amended, is to protect the integrty of the Deparment of Health and Human Services ' (HHS) 
programs as well as the health and welfare of beneficiares served by those programs. This 
statutory mission is cared out through a nationwide network of audits, investigations, and 
inspections conducted by three 010 operating components: the Office of Audit Services, the 
Office of Investigations, and the Office of Evaluation and Inspections. The 010 also informs the 
Secretary of HHS of program and management problems and recommends courses to correct 
them. 
OFFICE OF AUDIT SERVICES 
The OIO' s Offce of Audit Services (OAS) provides all auditing services for HHS, either by 
conducting audits with its own audit resources or by overseeing audit work done by others. 
Audits examne the performance of HHS programs and/or its grantees and contractors in 
caring out their respective responsibilities and are intended to provide independent 
assessments of HHS programs and operations in order to reduce waste, abuse, and 
mismanagement and to promote economy and efficiency throughout the Deparment. 
OFFICE OF INVESTIGATIONS 
The OIO' s Offce of Investigations (01) conducts crimial, civil, and admistrative 
investigations of allegations of wrongdoing in HHS programs or to HHS beneficiares and of 
unjust enrchment by providers. The investigative efforts of 01 lead to criminal convictions, 
, or civil money penalties. The 01 also oversees State Medicaid fraud 
administrative sanctions
control units which investigate and prosecute fraud and patient abuse in the Medicaid program. 
OFFICE OF EVALUATION AND INSPECTIONS 
The OIO' s Office of Evaluation and Inspections (OEI) conducts short-term management and 
program evaluations (called inspections) that focus on issues of concern to the Deparment, the 
Congress, and the public. The findings and recommendations contaned in these inspection 
reports generate rapid, accurate, and up-to-date information on the efficiency, vulnerabilty, and 
effectiveness of deparmental programs. 
This report was prepared in the Public Health and Human Services Branch under the direction of 
Emilie Baebel, Branch Chief. Project staff included: 
Mary Beth Clarke, R. Project Leader  W. Mark Krushat 
Ph., 
Penny R. Thompson  Barbara Tedesco 
Kathrn Pocock  Linda Moscoe  Department of Health and Human Services

OFFICE OF

INSPECTOR GENERAL

HOSPITAL REPORTING

OF ADVERSE DRUG REACTIONS

~t~ C;V.RVICES. 
Richard P. Kusserow 
INSPECTOR GENERAL 
'0 
OEI-12-90-01000 
lj ol~\'dm  EXECUTIVE SUMMARY

PURPOSE 
The purpose of this study is to: (1) determine the extent to which hospital pharacists are 
familiar with the Food and Drug Administration s Spontaneous Reportng System (SRS) for 
reporting adverse drg reactions (ADRs); (2) determine the nature and frequency of hospitals 
in-house ADR monitoring; and (3) identify any reasons why hospitals do not report ADRs to the 
FDA. 
BACKGROUND 
While extensive testing is conducted on al prescription drgs prior to marketing approval from 
FDA, not all adverse reactions are detected at this time, as some are extremely rare or occur only 
in special populations. Consequently, it is only after the wider use that occurs after the drg is 
marketed, which may include unapproved uses and different patient populations, that some 
ADRs are detected. FDA collects adverse drg reaction reports from pharaceutical 
manufacturers, medical professionals, postmarketing studies and the medical literature. 
Pharaceutical manufacturers are required to report all ADRs, while reportng from medical 
professionals is voluntar. 
FDA undertakes many activities to encourage reportng by medical professionals, includig pilot 
projects to increase physician reporting of ADRs and a task force to study hospita reporting. 
This report provides additional information about in-house ADR reporting programs in hospitals 
and hospital reporting of ADRs to FDA. 
METHODOLOGY 
Data for this survey were gathered by conducting a mail survey of 1260 hospital pharacy 
departments randomly selected from the American Hospital Association s listing of hospitals in 
the U.S. and stratified by size. Additionally, we conducted a literature review concentrating on 
reports of hospita ADR programs appearng in the medical literature. Finally, we conducted 
interviews with the Joint Commission on Accreditation of Healthcare Organizations and the 
American Society of Hospital Pharacists to obtain their views on hospita reporting of ADRs. 
FINDINGS 
Ninety-two percent of all hospitals know how to report adverse drg reactions (ADRs) to 
the FDA. However, 14 percent of small hospitals are unaware of the proper reporting 
procedure.  Overal, knowledge of how to report adverse reactions to FDA is quite high with less than ten 
percent unaware of FDA' s system and how to use it. However, a significant difference exists in 
the awareness level among hospitals of different sizes, with small hospitals much less likely to 
be aware of FDA' s reporting process. 
II.  Respondent hospitas are engaged in several aspects of ADR reporting; some activities 
are more commonly performed in medium and large hospitals. 
Our survey respondents indicated that their hospitals are conducting several activities as par of 
in-house ADR monitoring and reporting programs. These activities include collection of patient 
information at the time of the adverse event, routine screening of patient medical records, and 
training for hospital staff in how to detect and report ADRs. 
Ill.  There are several factors affecting hospital reporting of ADRs to FDA. 
A total of 51 percent of our respondent hospitals indicate that they reported no adverse drug 
reactions to FDA in 1989. This response was more common among the small hospitals (68 
percent) than the medium and large hospitals (42 and 29 percent, respectively). Regardless of 
the accuracy of these numbers, it would appear that there are factors affecting ADR reporting to 
FDA by hospitals. 
Hospitals indicate that they hesitate to report ADRs to the FDA when they are 
unsure that the drg caused the reaction. 
Fifty-seven percent of hospitals have policies in place 
requirng approval by an 
additional hospital committee or deparment before an ADR is reported to FDA. 
RECOMMENDATIONS 
To improve hospital reporting of adverse drg reactions, FDA should 
clarfy for hospitals 
the role of causality assessment when reportng adverse drg reactions to FDA. 
II.  FDA should evaluate the role of physicians in hospital reporting of adverse drug 
reactions. 
Ill.  FDA should sponsor pilot studies to further study reasons why hospitals hesitate to report 
ADRs to FDA and develop methods to encourage ADR reporting by hospitals. 
AGENCY COMMENTS 
Within the Department of Health and Human Services, the Public Health Service (PHS) 
provided comments to this report. The PHS concurred with our recommendations and were 
generally favorable about the report.  ...... ............ ...... ........ .... .......... .... .... .............. ...... ........ .......
TABLE OF CONTENTS

EXECUTIVE SUMMARY 
INTRODUCTION ......................................................................................................

Purose.............................................................................................................. ..

Background........................................................................................................ .

Methodology...................................................................................................... ..

FINDINGS................................................................................................................ ..

RECO MMEND ATIO NS ...........................................................................................

AGENCY COMMENTS .. 
APPENDIX A: Methodology and Statistical Analysis ........................................ A

APPENDIX B: Detailed Comments on the Draft Report .......................................
 INTRODUCTION

PURPOSE 
The purose of this study is to: (1) determne the extent to which hospital pharacists are 
famliar with the Food and Drug Administration s Spontaneous Reporting System (SRS) for 
reporting adverse drg reactions (ADRs); (2) determne the nature and frequency of hospitals 
in-house ADR monitoring; and (3) identify any reasons why hospitals do not report ADRs to the 
Food and Drug Admnistration. 
BACKGROUND 
The Food and Drug Admnistration (FA) defines an adverse drg reaction as the following: 
An adverse reaction is an undesirable effect, reasonably associated with the use of 
the drug, that may occur as part of the pharmacological action of the drug or may 
be unpredictable in its occurrence.  (21 CFR par 201) 
While extensive testing is conducted on  drgs prior to marketing approval from 
al prescription 
FDA, not all adverse reactions are detected at this time, as some are extremely rare or occur only 
in special populations. Consequently, it is only after the wider use that occurs after the drg is 
marketed, which may include unapproved uses and different patient populations, that some 
ADRs are detected. To acknowledge this situation and capture important additional information 
available after a drg s approval, FDA established the Spontaeous Reporting System. The SRS 
acts primarly as an early waring system indicating a potential relationship between an adverse 
drg. 
reaction and a given  FDA may then determine if additional studies are needed to confirm 
the adverse reaction. Eventually the information received through the SRS may be used to 
revise product labeling and alert medical professionals of new serious reactions. 
FDA receives the majority of ADR reports from pharaceutical manufacturers, medical 
professionals, and to a lesser extent from postmarketing clinical trals and the medical literature. 
Pharaceutical manufacturers are required to submit periodic ADR reports quarerly during the 
first three years of marketing a drg and annually thereafter. Reports of serious adverse 
reactions not listed in the drg s labeling must be submitted within 15 days, as well as increases 
in the frequency of labeled serious adverse reactions. FDA defines a serious ADR as one 
resulting in death, hospitalization, disability, congenital abnormality, or cancer. 
Although voluntar, direct physician reporting of adverse drg reactions has been shown to be an 
important contrbution to FDA's postmarketing safety data. In a study conducted by Rossi and 
Knapp, reporting by physicians and other medical professionals was shown to result in a higher 
proportion of labeling changes based on the number of reports filed in comparson to reports 
1 Direct 
from pharaceutical manufactuers.  reporting also allows FDA to contact the medical 
professional for additional information if necessar.  FDA encourages  medical professionals through a varety of programs, 
diect reporting by 
reminders, and educational materials. To encourage physician involvement, reporting forms are 
mailed to all practicing physicians several times a year. Additionally, FDA has sponsored pilot 
projects through several State health departments in an effort to increase community-based 
physician reporting of ADRs. The Rhode Island project has included a mail surey to identify 
barers to physician reporting and the distrbution of ADR reporting kits combined with 
2 FDA has also 
educational sessions to encourage FDA reporting. underten activities 
encouraging reporting by hospital pharacists, including informational kits for hospitals 
developing an ADR system and arcles in major professional jourals. Also, FDA has formed a 
task force composed of representatives from several major hospitals to formulate guidelines for a 
model hospital ADR program. 
Additionally, new requirements have been established by the Joint Commission on Accreditation 
of Healthcare Organizations (JCAHO). As a condition of accreditation, hospitals must have in 
place or develop an in-house monitoring and reporting program for ADRs. The primar 
priary 
objectives of these in-house hospital programs are  improved quality assurance and risk 
management so that optimal drg therapy is delivered to all patients. Additionally, these 
programs can provide valuable information concerning new adverse drg reactions. Adverse 
reactions of this type are of the greatest interest to FDA, since many of the adverse reactions that 
on are aleady known. 
hospitals wil collect information 
In light of FDA interest and the new JCAHO requirements hospita reporting of ADRs is worthy 
of additional attention. This study provides basic information about hospital ADR monitoring 
and reporting activities. 
METHODOLOGY 
Data were gathered from the following sources for this study. 
First, to determne awareness and usage of FDA' s ADR reporting system and in-house policies 
and procedures among hospitals, we conducted a mail survey of 1260 hospital pharacy 
departments. Hospitals were selected randomly from the American Hospital Association s listing 
of hospitals in the U.S. and stratified by size to ensure appropriate representation of small (less 
than 100 beds), medium (100 to 499 beds), and large (500 or more beds) hospitals. Large 
hospitals were oversampled at the request of FDA, because they have traditionally represented 
the greatest percentage of ADR reports from hospitals overall. We received a total of 826 usable 
surveys, resulting in an overall response rate of 66 percent. The survey results in this report are 
primarly presented by strata and are not projected to the universe of all hospitals in the U. 
since non-respondent hospitals in the stratum of small hospitals differed from our respondents. 
(Additional details regarding respondents, stratification, weighting and response rates are 
provided in Appendix A). 
Second, to obtain additional information concerning hospital ADR programs, we conducted a 
literature review concentrating on reports of hospital ADR systems appearng in the medical  literature. Third we conducted interviews with the Joint Commssion on Accreditation of 
Healthcare Organizations and the American Society of Hospital Pharacists to obtain their 
views on hospital reportng of ADRs.  .................. ~...~... .~.....~.....~. ..~...............~.....~......~...~......~...~......~ ~~..~...~...~~..~..~..~...~.~..~.~ .~..~.....~~.........................-.....-...... .". .'.."..."......... .. .... ...............................  .  ......-.................." .. ..,....~.- .~. ...~......,..~"....~...~.........~.....~...~.....~.. .. ... ." ..............."................
..............~..~.~..~.~..~.~.~~..~~~~~~~~~
FINDINGS 
Ninety-two percent of respondent hospitals know how to report adverse drug reactions 
percent of small hospitals are unaware of the proper 
(ADRs) to the FDA. However,  14 
reporting procedure. 
Overal, knowledge of how to report adverse reactions to FDA is quite high with less than ten 
percent unaware of FDA' s system and how to use it. However, a significant difference exists in 
the awareness level among hospitals of different sizes. Only 85 percent* of small hospitals (95% 
confidence interval (C.I.), 0.799 to 0.894) are aware of FDA reporting procedures compared to 
96 and 98 percent of medium and large hospitals (95% c.1., 0.931 to 0.978; and 0.957 to 0.992), 
respectively. 
The majority of hospitals (62 percent) receive information on FDA's ADR system directly from 
FDA. Other important information sources for hospitals about FDA's ADR system are 
professional journals and professional and continuing education. Professional jourals are most 
important as informational sources to large and medium sized hospitas. Similarly, educational 
programs are significant primarly to large hospitals. Among respondents of all sizes, 
pharaceutical manufacturers' representatives are not a significant source of information on how 
to report ADRs to FDA. 
Sources of Information Regarding FOAls ADR System 
Directly from FDA  Irr  ttit  ttIIrfrIfIrIffIIfffrtfr  ttttttttttttttt 
Professional 
Journal 
Pharmacy school! 
Continuing 
education program 
Pharmaceutical  20 40 
Manufacturers 
Representatie 
::tals 
als  Small Hospitls
Total 
1 00 beds 
* One percent of small hospitals did not respond to ths question. !., 
ll.  Respondent hospitals are engaged in several aspects of ADR reportng; some activities 
are more commonly performed in medium and large hospitals. 
Our survey respondents indicated that their hospitals are conducting several activities as par of 
in-house ADR monitoring and reporting programs. These activities include collection of patient 
information at the time of the adverse event, routine screening of patient medical records, and 
training for hospital staff in how to detect and report ADRs. A 
tota of 91 percent of the 
respondent hospitals have some type of data collection form for reporting ADRs. Among 
respondents, large hospitals (99 percent; 95% C.!., 0.975 to 0.997) are more likely to have forms 
for collecting ADR information, than medium (94 percent; 95% C.I. , 0. 910 to 0. 966) or small 
(85 percent; 95% C.  800 to 0.896). Seventy percent of the respondent hospitas use 
customized forms developed within the hospita for collecting ADR information. 
Slightly less than one-half of the respondents (47 percent) indicated that in their hospital patient 
medical records are routinely screened for signs of ADRs. Screening for adverse drg reactions 
may include periodically reviewing the patient s char, screening medication orders as they are 
received in the pharacy, and screening laboratory data. 
Slightly greater than one-half of all the respondents offer some type of periodic training or 
education for staff on how to detect and report ADRs. A greater percentage of large and medium 
hospitals (60 and 59 percent, respectively; 95% C.I. 0.553 to 0. 660 and 0.535 and 0.648) offer 
periodic training for hospital staff in detecting and reporting ADRs compared to small hospitals 
(40 percent; 95% c.1. , 0.331 to 0.461). Training methods used by hospitals range from 
traditional in-service lectures to innovative videotape presentations developed within the 
hospita1. 
llI.  There are several factors affecting hospital reporting of ADRs to FDA. 
A total of 51 percent of our respondent hospitals indicated that they reported no adverse drg 
reactions to FDA in 1989. This response was more common among the small hospitals (68 
percent; 95% C.I., 0.615 to 0.740) than the medium and large hospitals (42 and 29 percent, 
respectively; 95% c.!., 0.365 to 0.479 and 0.238 to 0.337). Regardless of the accuracy of these 
numbers, it would appear that there are factors limting ADR reporting to FDA by hospitals 
(greater detail of this statistic is provided in the Appendix). 
Hospitals indicate that they hesitate to report ADRs to the FDA when they are 
unsure that the drug caused the reaction. 
Fifty-one percent of hospitals hesitate to report ADRs to the FDA because they are 
uncertan whether the suspected drg actually caused the adverse reaction. This 
hesitation is of particular interest in light of the fact that FDA does not require positive 
proof of causality as a condition to report an ADR. In fact, a single report is generally 
insufficient to determne a definite cause and effect relationship between a drg and 
given adverse event.  Despite this, a majority of hospitas (74 percent) conduct follow-up to assess the 
likelihood of causality for at least all serious reactions. To assess causalty, hospitals may 
use several methods includig discontinuing and rechalenging with the suspected drg, 
application of one of several algorithms * , and evidence of similar reactions in the 
medical literature. Although discontinuing and rechallenging with the suspected drg is 
perhaps most useful, it may not be practical for 
paricularly severe reactions. Fifteen 
percent of hospitals responding to our surey rechallenge with the suspected drg to 
determne causalty. Use of algorithms solely is more common in large hospitals (22 
percent; 95% c.!., 0. 176 to 0.267) as opposed to medium (13 percent; 95% C.I., 0.086 to 
163) and small hospitals (4 percent; 95% C.I., 0.015 to 0.068). 
(* An algorithm is a formula which assigns numeric values to aspects of the adverse event which are used to 
predct the probability of a causal relationship with the suspected drg. 
Appropriately, 66 percent of hospitals hesitate to report to FDA when the adverse reaction is 
expected or not severe. This is consistent with the greater emphasis FDA places on the reporting 
of new serious reactions. If all hospitals were to report all of their observed ADRs, FDA would 
be overwhelmed with numerous reports with little significance. Other reasons hospitals mention 
for hesitating to report to the FDA include lack of time (11 percent), reporting to the 
manufacturer considered sufficient (8 percent), concern over legal 
liabilty (6 percent), lack of 
forms (5 percent), and not knowing how to report (4 percent). 
Reasons for Hesitating to Report ADRs to FDA 
Percentage of Respondents 
Small  Medium  Large 
Reasons for not Reporting  Total  (.:100)  (100 - 499)  (500+) 
Hospitals  Hospitals  Hospitals 
Reaction was expected/not severe 
Unsure that drg caused the reaction  52' 
Do not have the time 
Consider reporting to manufacturer 
sufficient 
Concern over legal liabilty 

Do not have forms (FA form 1639) 
Not  Not  Not  Not 
addititive  additive 
additive *  additive * 

*Respondents gave one or more reasons  Fifty-seven percent of hospitals have policies in place requiring approval by an 
additional hospital committee or department before an ADR is reported to FDA. 
In many hospitals the pharacy department may not have the authority to report ADRs to 
the FDA without approval or concurrence from the physician, commttees, or other 
departments within the hospital. The most frequently mentioned entity involved in ADR 
reporting is the Pharacy and Therapeutics (P & T) commttee. This committee, which 
often has a majority of physician members, is involved in the decision to report an ADR 
to FDA in 42 percent of hospitals. Similarly, concurence or approval by the prescribing 
physician is necessary in 25 percent of hospitals. Other commttees that are involved less 
frequently in the decision to report an ADR to FDA include Quality Assurance (13 
percent) and Risk Management (9 percent). Hospitals operated by the Veterans 
Administration (VA) are required to send reports of ADRs to the VA Central Office, 
instead of directly to FDA. 
Required Approval/Concurrence to Report an ADR to FDA 
Percentage of Respondents 
Small  Medium  Large 
Type of Approval/Concurrence  Total  (.:100)  (100 - 499)  (500+) 
Hospitals  Hospitals  Hospitals 
Pharacy & Therapeutics commttee 
Attending/rescribing Physician 
Quality Assurance commttee 
Risk Management 
No approval/concurrence required 
Not  Not  Not  Not 
addititive  additive 
additive *  additive * 
*Respondents gave one or more reasons 
In hospitals where approval is required by the prescribing physician or physician dominated 
committees, such as the P & T committee, ADR reporting to FDA may be subject to some of the 
barers of physician reporting. For example, while our respondents themselves did not rate 
liability concerns as a reason for not reporting to the FDA, several did note that it is a significant 
concern among physicians. Additionally, a few respondents commented that required approval 
or concurrence from Pharacy and Therapeutics or Quality Assurance Committees to report to 
FDA can be quite difficult to obtain. One respondent indicated that in his hospital the Risk 
Management Committee becomes anxious if ADRs are identified in patient discharge summares.  RECOMMENDATIONS

To improve hospital reportng of adverse drug reactions, FDA should clarify for 
hospitals the role of causality assessment when reportng adverse drug reactions 
FDA. 
The most important action FDA can take to improve ADR reportng from hospitals is to clarfy 
the role of causality assessment. Uncertnty over whether the drg caused the adverse reaction 
is the most significant reason why hospitals say they hesitate to report ADRs to FDA. Also, the 
majority of medium and large hospitals regularly conduct follow up to assess causality for 
serious adverse reactions. Oiven the difficulty of establishing a cause and effect relationship on 
the basis of one observed adverse reaction, there is a great probabilty that hospitas are not fiing 
reports that would be of use to FDA when analyzed collectively. FDA should develop some 
method to diectly communicate with hospitals the need to report adverse reactions even when 
definite causality cannot be determned. 
FDA should evaluate the role of physicians in hospital reportng of adverse drug 
reactions. 
Physicians and physician commttees are involved in ADR reporting in a significant percentage 
of the respondent hospitals. While the full impact of their involvement cannot be quantified, it is 
probable that physicians are in some way influencing ADR reporting. Any efforts undertaken by 
FDA to further encourage hospital reporting of ADRs should take physicians into consideration. 
Efforts targeted solely at hospital pharacists may not result in increased reporting to FDA if 
physicians involvement is not taken into account. 
HI.  FDA should sponsor pilot studies to  why hospitals hesitate to 
further study reasons 
report ADRs to FDA and develop methods to encourage ADR reporting by hospitals. 
FDA should take advantage of the current climate of interest in ADR monitoring and reporting 
that exists as a result of the new requirement from the Joint Commission on Accreditation of 
Healthcare Organizations that all hospitals develop in-house ADR programs. This period of 
heightened awareness offers an excellent opportunity to furher explore the reasons why 
reportg. 
hospitals hesitate to report ADRs to FDA and to find successful ways to encourage 
Hospitals var in their approaches to setting up these programs so that ADR monitoring and 
cared out. Pilot programs would offer FDA the opportunity to 
reporting are successfully 
examine hospital programs in greater detail and to determne what activities might be undertaken 
to increase reporting to FDA.  AGENCY COMMENTS

Within the Department of Health and Human Services, the Public Heath Service (PHS) provided 
comments to this report. The PHS concured with our recommendations and were generally 
favorable about the report. A detailed copy of the comments are provided in Appendix B.  NOTES

Rossi, A.c. and Knapp, D.E. Discovery of new adversy drg reactionis: A review of the 
Food and Drug Administration  JAMA 252:1030-1033, 
s spontaneous reporting system. 
1984. 
Scott, H.D. et al. Rhode Island physicians' recognition and reporting of adverse drg 
reactions: Increased physician s parcipation in post-marketing sureilance wil lead 
Rhode Island Medical Journal
greater understanding of adverse drug reactions. 

70:311-316, 1987. 
Berr, L.L. et  and specificity of three methods of detecting adverse drug 
al. Sensitivity 
reactions.  Am J Hosp Pharm  45:1534-1539, July 1988. 
Morgan, S.A. and Frank, J.T. Development of a videotape on adverse drug reactions. 
47:1340-1342, June 1990. 
Am J Hosp Pharm 
 APPENDIX A

Methodological Approach 
The objective of this study was to determine the level of awareness of FDA' s adverse drg 
reaction reporting system among hospitas and to profile in-house ADR reportng activities in 
hospitals. Surveys were mailed to the Directors of Pharacy Services for each of the hospitals 
in the sample. Directions were given for the surey to be completed by the Director or some 
other appropriate designee (profie of respondents may be found in Table A). No attempt was 
made to eliminate Federal or miltar hospials from the sample, as these hospitals are also 
potential sources of ADR reports for FDA. 
Design Specifcations and Sample Selection 
The sample was randomly selected from the 1987 American Hospital Association s (AH) 
listing of hospitals in the U. S. The sample was stratified by size (defined as the number of 
licensed beds accordig to AH) into thee groups: small (less than 100 beds), medium (100 to 
499 beds), and large (500 beds and over). An equal sample was drawn for each strata, resulting 
in an oversampling for the stratum of large hospitals due to the smaller universe of large 
hospitals. 
A size of approximately 1260 hospitals assumed a 40 percent response rate and a 95 percent 
confidence interval that would be within 5 percent of the tre reporting rate, with the 
hypothesized reporting rate assumed to be 10 percent for the small and medium strata and 20 
percent for the large stratum. In fact, we achieved a higher response rate and a higher rate of 
represents
reporting among the respondents. The precision of our results are therefore well 
within the 
parameters of the design.
Eight weeks after the mailing date, 826 sureys had 
been returned to our office. This 
a total response rate of 66 percent. The following table displays the response rate by individual 
strata. 
Response Rate by Hospital Size 
Hosoital Size (bv number of beds)  Response Rate 
Small(o:lOo)  217  52% 
Medium (100-499)  289  69% 
Large (500+)  320  76% 
Total  826  66%  Non-Respondent Analysis 
An importt consideration in surveys such as this tye is the bias that may be introduced into 
the results if the non-respondents are different than those that responded to the surey. To 
determne the presence of any bias, we contacted by telephone a miimum of ten hospitals per 
strata selected in the original sample that did not complete a survey. These non-respondent 
hospitals were asked the following key questions from the survey: (1) Are you aware of how to 
durg 
report an ADR to the FDA? (2) Did you report any ADRs to FDA  calendar year 1989? 
Finally, nonrespondents were asked why they chose not to paricipate in the surey. 
Among medium and large hospitas answers did not differ from those of the respondent 
hospitals. Nonrespondent small hospitals, however, difered significantly from those 
parcipating in our survey. Approximately one-hal of the nonrespondent hospitas in the small 
category did not have pharacy deparments. In these hospitals, we were unable to locate an 
individual with knowledge of or responsibilty for ADR reporting. As our results may be 
optimistic in the stratum of small hospitals we have chosen not to project our results to the 
universe of all hospitals in the U. 
Projected Number of ADRs 
In the survey hospitals were asked to indicate the approximate number of ADRs they reported to 
FDA durng the calendar year 1989. Respondents provided this information by checking the 
appropriate range of numbers for the reports they sent in. In the table below is a projection 
based on a representative number for each range, of the tota number of ADRs the respondent 
hospitals should have reported to FDA in 1989. These numbers were then weighted to the 
universe of each stratum to provide an estimation of the reporting from all hospitals in the U. 
It is interesting to note from this calculation that while large hospitals are providing the greatest 
number of reports per hospital, it appears that reports from medium hospitas may be constituting 
the largest percentage of the reporting activity.  ...
:;:;:;:::::::::::;:;:;:;:;:::;:;:;:;~:;~:;~:;~:;~:;~:;:;:;:;:;::::::;:;:::::::::::;:;:;:::::::;:::::::::;:::::::::::::::::;:::::::;:;:;:;:;:;:;:;:;:;:;:;:;:;:;:;:::::::::::::::::;:;::::::
Projected Number of ADRs Reported to FDA in 1989

Number of Respondent Mentions  Total Projected Number 
ADRs Re orted to FDA 
Small Medium  Small Medium 
Number of ADR  Large  Large 
499)  499) 
Reports  (0:100) (100- (500+)  (0:100) (100- (500+ ) 
Respondents sent to  Hospitals Hospitals Hospitals  Hospitals Hospitals Hospitals 
FDA in 1989 
147  122 
127  133  152.5  317.  332. 
22.  157.  277. 
11- 20  120  330 
::20  140  660 
Total (excluding 

213  285  317  210  735  1600 
Answer 
rfi/frrrr fffir  ttI 
ffjf(tft\(r ffrrrrftmrmrrrrr 
Calculated by using the midpoint of each interval, except for the :;20 category, where a value of20 was used. 
2 Calculated by weighting the estimated number to the universe of hospitals by strata, as provided below: 
Small  Medium  Larl!e 
Universe  3258  3296,  498 
Samnled  420  420  420 
Weil!ht  7571  8476  1.1857 
A- 3
 TABLE A 
Respondent Demographics 
Survey Particioant Job Title  Percenta2:e (n=826) 
Pharacy Director. Associate. Assistant 
Clinical Pharacist (drg information) 
Clinical Pharacist (general) 
Pharacist Supervisor 
Sta Pharacist

Other 
*inclutks Hospital Administrators and Nurses 
Teachin2 Affiiation  Percenta2:e (n=826) 
Affilatedlesearch 
U niversitv 
Communitvffeaching 
Community /Non-teaching 
Veterans Administration/Mlitar 
No Answer 
Financial Affliation  Percenta2:e (n=826) 
For Profit 
Not for Profit/Chartv 
Countv-operated 
State-operated 
Federally-operated  APPENDIX 

Detailed Comments on the Draft Report  --..-
&.  .. ,,:.,
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DEPARTMENT OF HEATH  HUMA SERVICES  Public Health Service
Memorandum 
JUL I 5 
Date 
From  Assistant Secretary for Health 
Hospital Reporting of Adverse 
Subject  PHS Comments on OIG Draft Report "
Drug Reactions, " OEI-12-90-0 1000 
Inspector General, 

report. 
Attached are the PHS comments on the subj ect draft 
con cur wit h e a c h 0 f the r e co mm end at ion s  an d h a ve  t a ken 0 r pIa n
them. 
to take actions to implement 
o. IV 
Mason, M.  , Dr.

Attachment 
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OEGC/XIG  SEC 
DATESE  COMMENTS OF THE PUBLIC HEATH SERVICE ON THE OFFICE 
GENERA (OIG) DRAT REPORT, " HOSPITAL REPORTING 
OF INSPECTOR 
OF ADVERSE DRUG REACTIONS, " OEI-12-90-01000, MAY 1991 
General Comments

Although 
We found the OIG draft report informative and useful. 
the report shows that knowledge of how to report adverse drug

Admnistration 
experiences  ood and Drug  (FDA) is 
qui te high, F(ADDEA) 'to tshe   Center for Drug Evaluation and Research (CDER) 
will continue to work for greater understanding and use of the

FDA system by all health care providers. Over the past several

years, CDER'  prove all aspects of the system have

s efforts to  numer of reports 
led to a significant increase in the annual 
submitted--increasing from 38, 854 in 1985 to 75, 230 in 1990. 
CDER is committed to continue- its efforts in this area.

portance of hospital ADE

We share the OIG' s 
reporting.  concerns about the 
Hospi tal based health care workers make a significant 
contribution to the FDA' s Spontaneous Reporting System, both

through direct reports to FDA and reports submitted to

FDA. 
CDER will continue its 
manufacturers and then forwarded to 
efforts to assure that physicians and other hospital providers

are knowledgeable about the procedure for ADE reporting and

continue to encourage them to report suspected ADEs without

regard to causality assessment.

This OIG report refers to episodes of adverse reactions as

adverse drug reactions (ADR). Within FDA, these are known as 
adverse drug experiences (ADE). The PHS comments follow FDA' 
nomenclature. 
OIG Recommendation

reactions, FDA

To improve hospital reporting of adverse drug 
should clarify for hospitals the role of causality

FDA. 
assessments when reporting adverse drug reactions to 
PHS Comment

clarify 
numer of steps to 
We concur. CDER has already taken a 
and promote its ADE reporting requirements to manufacturers and

health care providers.

In 1985 (amended in 1987), FDA clarified its ADE reporting

(21 CFR 314. 80 and

requirements as they relate to manufacturers 
305). 
21 CFR 310.  These regulations require manufacturer 
state: 
reporting irrespective of any causality assessment and 
A report or information submitted by an applicant

under this section (and any release by FDA that the

report of infor.ation) does not necessarily reflect a

conclusion by the applicant or FDA that the report
 or information constitutes an admission that the

drug caused or contributed to an adverse effect.

admt, 
An applicant need not  and may deny, that the 
report or information submitted under this section

consti tutes an admission that the drug caused or

80 (1)). 
contributed to an adverse effect" (21 CFR 314. 
FDA has also encouraged health providers to report adverse

suspicion 
experiences to the Agency if there is a "  " that the drug 
is related to the adverse experience. The Agency has discouraged

causality assessment as a prerequisite for ADE reporting in an

effort to be inclusive rather than exclusive.

In writing about reporting adverse experiences to FDA, non-FDA 
sources have also helped educate health providers to report

suspected adverse reactions and have emphasized that a causality

reporting. 
assessment is net needed for 
When hospitals request information on adverse experience

reporting, CDER' s Office of Epidemiology and Biostatistics

routinely sends a packet of information. This packet of 
states: 
information was recently updated and specifically 
Please note that FDA is interested in all such events

associated  with a drug. Thus  not
, causality need 

established before deciding to report an adverse drug

reaction to FDA.

In sumary, CDER will continue to explain FDA' s position on

causali ty which is that the suspicion of a relationship between a

reporting. 
drug and an adverse experience is enough to initiate 
required. 
No causality assessment is 
OIG Recommendation 
tal 
FDA should evaluate the role of physicians in hespi 
reporting of adverse drug reactions.

PHS Comment

area. 
We concur. FDA plans to continue its efforts in this  For 
reporting. 
some time, FDA has been concerned about physician ADE 
For example, in an effort to understand physician behavior in

reporting ADE and to assess ways to Lmprove direct reporting of

ADEs, FDA initiated a contract research program through State

1985. 
health departments in  Maryland and Rhode Island were 
awarded the first two pilot test contracts to survey physicians'

existing attitudes and to design interventions to promote and

increase ADE reporting.
 To investigate the feasibility of increasing ADE reporting

wi thin hospitals, a third pilot contract was awarded to 
1986. In 
Mississippi in  1987, Massachusetts and Colorado were 
awarded contracts to use and build on the interventions

developed by the first three States. The program has been

successful in stimulating the reporting of ADEs by physicians.

Further, FDA staff have given numerous presentations and written

a numer of 
papers on physicians' ADE reporting. 
Though we have long encouraged physician ADE reporting, we

very complex with

also recognize that hospital reporting  is 
many hospitals having several pharmacies and satellites, many

physicians and other health care providers and an intricate

departments. and commttees. 
infrastructure of  Addi tionally, most
hospi talized patients are on more than one drug and any ADE can 
be confounded by these drugs, disease and other factors.

Nonetheless, we maintain that hospital reporting strategies

should not be limi ted to any professional group. 
FDA continues 
to encourage reporting from all health professionals.

OIG Recommendation 
furher 
FDA should sponsor pilot studies to  study reasons 
why hospitals hesitate to report ADRs to FDA and develop

methods to encourage ADR reporting by hospitals.

PHS Comment

We concur in principle with the need for further study and

promotion but believe it should be incorporated within FDA'

effort. 
current efforts rather than a separate 
FDA' s CDER shares the interest in learning more about reporting 
patterns and practices and has a numer of targeted ongoing
ties which it believes will achieve this purpose. 
acti vi 
CDER is 
continuing to learn about ADE reporting practices and patterns

from the Epidemiologic Cooperative Agreements, State Contracts,

ties. 
and other acti vi 
The current ADE reporting contracts with the State Health

Departments in Mississippi, Rhode Island and Colorado indicate

the requirement for continual conduct- of educational and

promotional interventions geared toward increasing the quantity

hospitals. 
and quality of ADE reports coming from  Workshops such 
as the June 1989 Rhode Island Workshop on ADE Monitoring in

Hospi tals have been held by all of the contractors. These 
seminars include information on FDA' s goals and objectives for

ADE monitoring.
 Two new cooperative agreements were awarded in May and June 1991

systems. 
The first 
that relate to ADE monitoring and reporting 
is based on a national network of clinical phar.acists that seeks

to harness the adverse drug event monitoring activities required

Commssion on Accreditation of 
of hospitals by the Joint 
Heal thcare Organizations to create a systematic mechanism for 
ADEs. 
collecting comprehensive data on  The second proposes to 
initiate routine safety surveillance of newly marketed drugs by

establishing a signal detection system in a large health

maintenance organization.

In sumary, we believe that FDA' s efforts fully satisfy the

intent of the OIG recommendation.

Technical Comments

Executi ve Sumarv, Backaround, Fourth Line 
The report uses the word " untested" to inaccurately 
drugs. In order 
describe unapproved uses of marketed 
word 
convey a more accurate meaning, we recommend that the 
untested. 
unapproved" be substituted for the word "
2 .  Introduction, Backaround, Second Paraaraph, Fourth Line 
numer 
Same as  1 above.