Department of Health and Human Services


OFFICE OF


INSPECTOR GENERAL


HOSPITAL REPORTING


OF ADVERSE DRUG REACTIONS


V.RVICES. 

Richard P. Kusserow 

INSPECTOR GENERAL '0 

lj \'dla 

mL Y 1991 
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, 

administrative sanctions, or civil money penalties. The 01 also oversees State Medicaid fraud 

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. Ph., Project Leader W. Mark Krushat 

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 

lj ol~\'dm OEI- 12-90-01000 
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 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. 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 

reaction and a given drg. 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 

from pharaceutical manufactuers. 

1 Direct reporting also allows FDA to contact the medical 

professional for additional information if necessar. 
FDA encourages diect reporting by medical professionals through a varety of programs, 

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 

educational sessions to encourage FDA reporting.2 FDA has also 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 

objectives of these in-house hospital programs are priary 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 

hospitals wil collect information on are aleady known. 

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 

(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. 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 

Manufacturers 

Representatie 20 40 

::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 further study reasons why hospitals hesitate to 

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 

hospitals hesitate to report ADRs to FDA and to find successful ways to encourage reportg. 

Hospitals var in their approaches to setting up these programs so that ADR monitoring and 

reporting are successfully cared out. Pilot programs would offer FDA the opportunity to 

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 s spontaneous reporting system. JAMA 252:1030- 1033, 

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 al. Sensitivity and specificity of three methods of detecting adverse drug 

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. 

Am J Hosp Pharm 
 47:1340- 1342, June 1990. 
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 

reporting among the respondents. The precision of our results are therefore well within the 

parameters of the design. represents 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 

report an ADR to the FDA? (2) Did you report any ADRs to FDA durg 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 

Number of ADR Small Medium Large Small Medium Large 

Reports (0:100) (100-499) (500+) (0:100) (100-499) (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) 

U niversitv Affilatedlesearch 

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 
&. . .. .. ,,:., 

..() . 

DEPARTMENT OF HEATH HUMA SERVICES Public Health Service

Memorandum 

JUL I 5 

Date 

From Assistant Secretary for Health 

Subject PHS Comments on OIG Draft Report " Hospital Reporting of Adverse 

Drug Reactions, " OEI-12-90-0 1000 

Inspector General, 


Attached are the PHS comments on the subj ect draft report. 

an d h a ve t a ken 0 r pIa n

con cur wit h e a c h 0 f the r e co mm end at ion s 

to take actions to implement them. 

o. IV 

Mason, M. , Dr.


Attachment 

:: ;\1 rT

:I! 

..i 

PDIG 

DIGDIGDIGAIG-MP 

OGC/IG EX SEC 

DATESE 

10 
COMMENTS OF THE PUBLIC HEATH SERVICE ON THE OFFICE 

OF INSPECTOR GENERA (OIG) DRAT REPORT, " HOSPITAL REPORTING 

OF ADVERSE DRUG REACTIONS, " OEI-12-90-01000, MAY 1991 

General Comments


We found the OIG draft report informative and useful. Although 

the report shows that knowledge of how to report adverse drug
 experiences (ADE) to the ood and Drug Admnistration (FDA) is 

qui te high, FDA' s 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' s efforts to prove all aspects of the system have


led to a significant increase in the annual numer of reports 

submitted--increasing from 38, 854 in 1985 to 75, 230 in 1990. 

CDER is committed to continue- its efforts in this area.


We share the OIG' s concerns about the portance of hospital ADE


reporting. 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


manufacturers and then forwarded to FDA. CDER will continue its 

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


To improve hospital reporting of adverse drug reactions, FDA


should clarify for hospitals the role of causality


assessments when reporting adverse drug reactions to FDA. 

PHS Comment


We concur. CDER has already taken a numer of steps to clarify 

and promote its ADE reporting requirements to manufacturers and


health care providers.


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


requirements as they relate to manufacturers (21 CFR 314. 80 and


21 CFR 310. 305). These regulations require manufacturer 

reporting irrespective of any causality assessment and state: 

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.


An applicant need not admt, and may deny, that the 

report or information submitted under this section


consti tutes an admission that the drug caused or


contributed to an adverse effect" (21 CFR 314. 80 (1)). 

FDA has also encouraged health providers to report adverse


experiences to the Agency if there is a " suspicion " 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


assessment is net needed for reporting. 

When hospitals request information on adverse experience


reporting, CDER' s Office of Epidemiology and Biostatistics
 routinely sends a packet of information. This packet of 

information was recently updated and specifically states: 

Please note that FDA is interested in all such events


associated with a drug. Thus , causality need 
 not

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


drug and an adverse experience is enough to initiate reporting. No causality assessment is required. 

OIG Recommendation 

FDA should evaluate the role of physicians in hespi tal 

reporting of adverse drug reactions.


PHS Comment


We concur. FDA plans to continue its efforts in this area. For 

some time, FDA has been concerned about physician ADE reporting. 

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


health departments in 1985. 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 

Mississippi in 1986. 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


also recognize that hospital reporting is very complex with


many hospitals having several pharmacies and satellites, many


physicians and other health care providers and an intricate


infrastructure of departments. and commttees. 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 

FDA should sponsor pilot studies to furher 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'


current efforts rather than a separate effort. 

FDA' s CDER shares the interest in learning more about reporting 

patterns and practices and has a numer of targeted ongoing acti vi ties which it believes will achieve this purpose. CDER is 

continuing to learn about ADE reporting practices and patterns


from the Epidemiologic Cooperative Agreements, State Contracts,


and other acti vi ties. 

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


and quality of ADE reports coming from hospitals. 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


that relate to ADE monitoring and reporting systems. The first 

is based on a national network of clinical phar.acists that seeks


to harness the adverse drug event monitoring activities required


of hospitals by the Joint Commssion on Accreditation of 

Heal thcare Organizations to create a systematic mechanism for 

collecting comprehensive data on ADEs. 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 

describe unapproved uses of marketed drugs. In order 

convey a more accurate meaning, we recommend that the word 

unapproved" be substituted for the word "untested. 

2 . Introduction, Backaround, Second Paraaraph, Fourth Line 

Same as numer 1 above.