16 Quality of Spon Reporting

8/13/2019 16 Quality of Spon Reporting

1/5

ORIGINAL REPORT

Quality check of spontaneous adverse drug reaction reportingforms of different countriesy

M. S. Bandekar, S. R. Anwikar and N. A. Kshirsagar *,z

Department of Infectious Diseases and Department of Interdisciplinary Research and Technology, Maharashtra University of HealthSciences, Maharashtra, India

SUMMARY

Adverse drug reactions (ADRs) are considered as one of the leading causes of death among hospitalized patients. Thus reporting of adverse

drug reactions become an important phenomenon. Spontaneous adverse drug reaction reporting form is an essential component and a majortool of the pharmacovigilance system of any country. This form is a tool to collect information of ADRs which helps in establishing the causalrelationship between the suspected drug and the reaction. As different countries have different forms, our aim was to study, analyze thesuspected adverse drug reaction reporting form of different countries, and assess if these forms can capture all the data regarding the adversedrug reaction. For this analysis we identified 18 points which are essential to make a good adverse drug reaction report, enabling propercausality assessment of adverse reaction to generate a safety signal. Adverse drug reaction reporting forms of 10 different countries werecollected from the internet and compared for 18 points like patient information, information about dechallengerechallenge, adequacy ofspace and columns to capture necessary information required for its causality assessment, etc. Of the ADR forms that we analyzed, Malaysiawas the highest scorer with 16 out of 18 points. This study reveals that there is a need to harmonize the ADR reporting forms of all thecountries because there is a lot of discrepancy in data captured by the existing ADR reporting forms as the design of these forms is different fordifferent countries. These incomplete data obtained result in inappropriate causality assessment. Copyright # 2010 John Wiley & Sons, Ltd.

key words pharmacovigilance; spontaneous ADR reporting forms; adverse drug reactions

Received 22 March 2010; Revised 7 April 2010; Accepted 22 May 2010

INTRODUCTION

Adverse drug reactions are considered as one of theleading causes of death among hospitalized patients.1

They are defined as a noxious, unintended effect of adrug, occurring at normal doses in humans forprophylaxis, diagnosis or therapy of disease, or forthe modification of physiological function.2 Infor-mation about adverse drug reactions (ADRs) can be

obtained through data from preclinical studies and

clinical trials but rare adverse reactions, which occuronly in a small percentage of cases, after a long periodof drug use or drug interactions with other establishedmedications may not be detected during clinical trials.For ADRs not discovered during clinical trials to bedetected, investigated and communicated, there is aneed for an extensive post-marketing pharmacovigi-lance of all medicines.

The responsibility of any drug authority is to ensure

the safety, efficacy, and quality of all marketedproducts. Pharmacovigilance is the science andactivities relating to the detection, assessment, under-standing, and prevention of adverse effects or any othermedicine-related problem.3

Pharmacovigilance can be done by various methodslike cohort studies, prescription event monitoring, etc.but spontaneous ADR reporting is a widely usedmethod of pharmacovigilance. It is used to generatehypotheses and signals about potential hazards of

pharmacoepidemiology and drug safety (2010)Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/pds.2004

* Correspondence to: N. A. Kshirsagar, Department of Infectious Diseasesand Department of Interdisciplinary Research and Technology, MaharashtraUniversity of Health Sciences, Maharashtra, India.

E-mail: [email protected] declare no conflict of interest.zDirector of Department of Infectious Diseases and Department of Inter-disciplinary Research and Technology, Maharashtra University of HealthSciences, Maharashtra, India. Emeritus Professor in Department of ClinicalPharmacology, Seth GS Medical College and King Edward MemorialHospital, Acharya Donde Marg, Parel, Mumbai, India.

Copyright # 2010 John Wiley & Sons, Ltd.


2/5

marketed drugs that require further investigation.Spontaneous reporting of suspected ADRs is particu-larly useful in identifying rare or delayed reactions, assuch a system enables medicines to be monitoredthroughout their lifetime.4 Most of the countries have

National Pharmacovigilance program center/s or unit/swhich carry out the adverse drug reaction monitoring.These centers are mainly concerned with the collectionof spontaneous and suspected ADR reports, carry outcausality assessment, and submit to regulatoryauthority. The reports are then sent to the WHOsADR Monitoring Center at Uppsala, Sweden wherethis information is pooled and unexpected reactions arewatched for when data mining methods are used; alsosuspected ADRs are sent out as signals to the nationalpharmacovigilance centers.

Spontaneous adverse drug reaction reporting formis an essential component and a major tool of the

pharmacovigilance system of any country. This form isa tool to collect information of ADRs which helps inestablishing the causal relationship between thesuspected drug and the reaction. If relevant informationregarding ADR is not adequately captured then it is ofno use for the regulatory authority as no conclusion canbe drawn from those data. Every country has developedits own spontaneous ADR reporting form for datacollection which is used by them to capture infor-mation about an adverse event. The newsletter ofWHO Pharmaceuticals has also cited the need for ageneric form for spontaneous reporting of adverse drug

reactions.

4

As different countries have different forms, our aimwas to study, analyze the suspected adverse drugreaction reporting form of different countries, andassess if the forms can capture all the data regardingthe adverse drug reaction. For this analysis, weidentified 18 points which are essential to make agood adverse drug reaction report enabling propercausality assessment of adverse reaction to generatea safety signal. The characteristics of good casereport include details about patient information,description of adverse event, temporal relationshipdrug administered, use of concomitant drug, rechal-

lenge, dechallenge, etc.

METHOD

Adverse drug reaction reporting forms of 10 differentcountries were collected from the internet andcompared for 18 points like patient information,information about dechallengerechallenge, adequacyof space and columns to capture necessary informationrequired for its causality assessment, etc. (Table 1).

Presence of different elements is expressed as yes(H) or no (T); presence of each element is scored asone mark, absence as zero and scores are totaled.

RESULTS

All the ADR forms which were studied had asked fordetailed patient information like age, sex and weight,list of suspected drugs, outcome of the reaction, andalso start and stop date of reaction and drugs. The fewimportant points that were missing from the ADRforms were information about allergic status, whichwas not asked for in the ADR forms of Pakistan, UK,and Kenya. Information related to pregnancy statuswas only asked for in the ADR forms of Pakistan andKenya. Another most important information requiredfor causality assessment is dechallenge which does notfeature on the ADR forms of Pakistan, UK, Australia,

and South Africa. Pakistan, Kenya, and Australia havenot asked for information on rechallenge either(Tables 1 and 2).

Of the ADR forms that we analyzed, Malaysia wasthe highest scorer with 16 out of 18 points. Pakistanfared below 50% on the 18-point scale, followed byAustralia, South Africa, UK, India, USA, Kenya, andSouth Africa.

DISCUSSION

The different parameters that were used to study theforms were the information regarding demographic

details of patients as crucial information regarding age,sex can be obtained which helps in correlation,details(Author: sense not clear. Please check.) aboutthe description of ADR helps us to get a detailedunderstanding of the ADR, the drug administered,concomitant medications to check for any drugdruginteractions, etc.

Requirement of information on the prior allergic statusand whether the patient is allergic to any drug isimportant. It should be considered because if patient hasa history of allergy to a particular drug and the same drugis administered then it will affect the causalityassessment of ADR resulting from such a case.

Pregnancy status is an important parameter for thecausality assessment of ADR in female patients. Forexample, if a patient had experienced nausea andvomiting, it may not be necessarily because of drug butcould be because of the patients pregnancy status.

The administered dose,route and frequency areimportant parameters which helps us to know whetherthe ADR would have been caused because of incorrectdose and/or frequency for the suspected drug. In thatcase it could be wrongly interpreted as ADR. Also this

Copyright # 2010 John Wiley & Sons, Ltd. Pharmacoepidemiology and Drug Safety, (2010)

DOI: 10.1002/pds

m. s. bandekar ET AL.


3/5

Table1.

Assessmentofspontaneousadversedrugreactionreportingform

ofdifferentcountries

Contents

Country

India5

Pakistan

6

USA7

UK8

Kenya9

Malaysia10

Canada1

1

Australia1

2

South

Africa1

3

Tanzania14

Patientsinformation

H

H

H

H

H

H

H

H

H

H

Pregnancystatus

H

H

Allergicstatus

H

H

H

H

H

H

H

Diagnosis

H

H

H

H

H

H

H

H

Descriptionofreaction

H

H

H

H

H

H

H

H

H

Properspace

Nospace

Properspace

Properspace

Lessspace

Medium

space

Properspace

Properspace

Lessspace

Lessspace

Listofsuspecteddrugs

H

H

H

H

H

H

H

H

H

H

Onlytw

odrugs

excluding

conco

mitant

medication

Verylessspace.

Onlysingle

drugcanbe

entered

Onlytwodrugs

excluding

concomitant

medication

Properspace

available

toentermore

t

hantwodrugs,

excluding

concomitant

medication

Tendrugsname

canbeentered

including

concomitant

drugs

Properspace

availableto

enterm

ore

thantwodrugs,

includi

ng

concomitant

drugs

Onlytwodrugs

excluding

concomitant

medication

Sixdrugs

including

concomitant

medication

Six

drugs

including

concomitant

med

ication

Threeto

fourdrugs

excluding

concomitant

medication

Dose,frequencyofdrugs

H

H

H

H

H

H

H

H

H

Noseparate

spaceis

available

Spaceforconcomitant

drugs

H

H

H

H

H

H

H

H

H

Nospace

available

Noseparate

spaceavailable

butitincluded

insuspecteddrug

Noseparate

spaceavailable

butitincluded

insuspected

drugcolumn

Noseparate

spaceavailable

butitincluded

insuspected

drugcolumn

Noseparate

space

available

butit

included

insu

spected

drug

column

Startdateandstop

dateofsuspecteddrugs

H

H

H

H

H

H

H

H

H

H

Dateofstopping

notmentioned.

Durationof

treatmentis

mentioned

Relevanthistoryofpatients

H

H

H

H

H

H

H

H

H

Actionstaken

H

H

Severity

H

H

H

Causality

H

H

Outcome

H

H

H

H

H

H

H

H

H

H

Dechallenge

H

H

H

H

H

H

Rechallenge

H

H

H

H

H

H

H

TreatmentofADR

H

H

H

H

H

H

Lotno,expirationdate

H

H

H

H

H

H

Noseparate

spaceis

available,

mentioned

inspace

ofsuspected

dr

ugsinformation


DOI: 10.1002/pds

QUALITY CHECK OF ADVERSE DRUG REACTIONs


4/5

provides us with vital information on whethermedication errors, if so have occurred. All the countriesexcept Pakistan had space to enter description ofreaction, list of concomitant drugs, dose, and frequency

of drugs. Relevant history of patient was mentioned inthe forms of all countries except Kenya whereas theactions taken were asked only in two countries, viz. UKand Kenya.

The mandatory information required for causalityassessment includes information on temporalrelationship, dechallenge, and rechallenge of theadministered drug. Of the forms analyzed, infor-mation regarding dechallenge is not asked for inPakistan, UK, and Australia whereas rechallenge isnot mentioned in Pakistan, Kenya, and Australia.Only Kenya and Malaysia asked for causality to be

written on spontaneous ADR report forms and India,Pakistan, Kenya, and USAs forms do not haveseparate column for treatment of ADR as mentionedin other countries. High scoring of Malaysia showsthat spontaneous ADR reporting form of this countryis capable of capturing maximum data about adversedrug reaction and thus this form will help to generateproper safety signals.

This study reveals that there is a need to harmonizethe ADR reporting forms of all the countriesbecause there is a lot of discrepancy in data capturedby the existing ADR reporting forms as the design ofthese forms is different for different countries. These

incomplete data obtained result in inappropriatecausality assessment of ADRs and possible signaldetection, for example, a certainly occurring ADRcould be wrongly interpreted as unlikely or notassessable due to lack of data. The signal detectionprocess at Uppsala Monitoring Center collates theADRs from all countries; while in fact there could bevariation between the data received from differentcountries, at least one reason may be the variation in theADR form itself.

CONCLUSION

The WHO receives information of the adverseevents from all the countries that are members ofthe international drug monitoring program. Thesedata are collated to generate potential signals;

therefore, the data received by the WHO have to beuniform and complete to draw meaningful con-clusions. Each country has its own spontaneousreporting form as per the individual countriesrequirements. However, our study reveals that thespontaneous reporting form from different countriesis inadequate to capture detailed information.Therefore, there should be international guidelinesand checklists for the inclusion of mandatoryinformation needed for causality assessment fordrafting and designing of spontaneous reportingform by countries.

The Council for International Organization ofMedical Sciences (CIOMS) (form which is the onlyinternational paper form used presently for spon-taneous reporting of adverse drug reactions tocollect data uniformly from all countries is incom-plete with respect to the information asked for theoutcome of the adverse drug reaction i.e., the formdoes not have an option for filling if the adversereaction caused congenital anomaly and othermedically important conditions. The most importantthing missing is the reporter information which is oneof the important criteria for accepting that the reportas valid.

Therefore, the introduction of guidelines for devel-oping an effective spontaneous reporting form tocapture complete adverse event-related information byWHO is the need of the hour.

Table 2. Scores of different countries

Sr. No. Country Score out of 18

1 India 132 Pakistan 63 USA 134 UK 125 Kenya 136 Malaysia 167 Canada 148 Australia 129 South Africa 1210 Tanzania 14

KEY POINTS

Spontaneous ADR reporting form is a major toolof the pharmacovigilance system of any country.

The ADR reporting forms is different for differentcountries thus leading to a lot of discrepancy indata captured by it.

The WHO ADR monitoring centre collatesinformation it receives from different counties.

Non-uniformity of the form leads to WHOdatabase itself being incomplete. Thus there isa need to harmonize the ADR reporting forms ofall the countries to capture complete adverseevent-related information.


DOI: 10.1002/pds

m. s. bandekar ET AL.


5/5

REFERENCES

1. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drugreactions in hospitalized patients: a metaanalysis of prospective studies.

JAMA 1998; 279: 12001205.2. EdwardsIR, Aronson JK.Adverse drugreactions: definitions, diagnosis

and management. Lancet2000; 356: 12551259.

3. World Health Organization.WHO Policy Perspectives on MedicinesPharmacovigilance: Ensuring the Safe Use of Medicines. Geneva2004.

4. Sten Olsson. The need for a generic form for spontaneous reporting ofdrug related problems Pharma Newsl 2007; 1: 79.

5. Central Drugs Standard Control Organization. Available from: http://www.cdsco.nic.in Accessed on [20 March] 2009.

6. Drug Control Organization Ministry of Health. Adverse Drug ReactionReporting Form, Pakistan. Available: http://www.dcomoh.gov.pkAccessed on [20 March] 2009.

7. U.S. Food and Drug Administration. Adverse Drug Reaction ReportingForm, United States of America. Available: http://www.fda.gov/med-watch Accessed on [19 March] 2009.

8. The Medicines & Healthcare Products Regulatory Agency (MHRA).

Adverse Drug Reaction Reporting Form, United Kingdom. Available:http://www.mhra.gov.uk Accessed on [22 March] 2009.

9. Pharmacy and Poisons Board Kenya Adverse Drug ReactionReporting Form, Kenya. Available: http://www.pharmacyboardkenya.org Accessed on [20 March] 2009.

10. National Pharmaceutical Control Bureau. Adverse Drug Reaction

Reporting Form, Malaysia. Available: http://www.bpfk.gov.myAccessed on [20 March] 2009.11. Health Canada. Adverse Drug Reaction Reporting Form, Canada.

Available: http://www.hc-sc.gc.ca Accessed on [25 March] 2009.12. Therapeutics Goods Administration, Adverse Drug Reaction Reporting

Form, Australia. Available: http://www.tga.gov.au Accessed on [22March] 2009.

13. Health Kwazulu-Natal. Adverse Drug Reaction Reporting Form, SouthAfrica. Available: http://www.kznhealth.gov.za Accessed on [20March] 2009.

14. Tanzania Food and Drugs Authority Adverse Drug Reaction ReportingForm, United Republic of Tanzania. Available: http://www.tfda.or.tz/adr/html Accessed on [25 March] 2009.


DOI: 10.1002/pds

QUALITY CHECK OF ADVERSE DRUG REACTIONs

Documents

16 Quality of Spon Reporting