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Primary care and Pharmacy: 4. large contributions to national adverse reaction reporting by pharmacists in Australia

Con Berbatis
A Pharmacy Researcher Perspective

Issue 72: June 2008
Page: 1 of 1 Author's Profile | Send to a Friend | Printer Version

Editor: In Australia, less than 2% of the more than 600,000 cases of severe adverse drug events (ADEs ) encountered yearly by GPs are reported to the Adverse Drug Reactions Advisory Committee (ADRAC). Community pharmacists’ contribution to ADRAC more than doubled to 23.1% of all reports from primary care sources after 2004 compared to the period 1999-2003. The number of reports submitted to ADRAC from hospitals represented nearly 5% of over 80,000 cases of severe ADEs managed each year in Australia’s hospitals. Hospital pharmacists have submitted most of the reports to ADRAC from Australia’s hospitals.
Con Berbatis discusses pharmacists’ impressive contributions to adverse reaction reporting and the potential to contribute further in practice and research in Australia.

1.0 Background and aim
The May i2P report in this series showed the national trend and pattern of sources of adverse drug reactions (ADRs) received and analysed from 1991 to 2008 (Figure 1) by the Adverse Drug Reactions Monitoring Unit (ADRMU) and reported by Australia’s Adverse Drug Reactions Advisory Committee (ADRAC). 1

The ADRMU and ADRAC are agencies under the control of the Therapeutic Goods Administration (TGA) within the Australian Government’s Department of Health and Ageing. 2 The terminology and procedures for the national monitoring of ADRs adopted in this report are based on guidelines published by the TGA in November 2007.2

General practitioners (GPs) in Australia reported that they encountered more than 600,000 cases of severe Adverse Drug Events (ADEs) in 2003 . 1 Severe ADEs refer to those which result in ceased medicines, limited daily activity, or result in hospitalisation. Community pharmacists reported that they declined to dispense prescribed medicines to over an estimated 300,000 people annually in 2002 for a suspected ADE. 1 This number in pharmacies probably represents a sub-set of those reported by GPs.

Based on the numbers of reports submitted to ADRAC from primary care sources as the numerator and over 600,000 cases of ADEs reported by GPs in 2003 as the denominator , less than 2% of severe ADEs encountered by GPs in primary care were reported by ADRAC. 1 In comparison, the numbers of hospital reports submitted to ADRAC by hospitals were estimated to represent nearly 5% of the more than 80,000 reported cases of severe ADEs managed in hospitals in 2003-04.1

The aims of this study were to :
* rank the national contributions by community and hospital pharmacists to ADRAC ; and
* compare ADRAC and the FDA’s safety monitoring or ‘pharmaco-vigilance’ performance in the numbers of ADE reports received after 2002.

Figure 1. Sources of adverse drug reactions reports in Australia to ADRAC 1990 to March 2008. The numbers are by 12 months ending 30 June .
[Source : ADRMU, Woden (ACT, Australia), April 2008]

2.0 The contribution to ADRAC by pharmacists from 1999 to 2008.
For the purposes of comparison in this report, the ‘ percentage community pharmacy contribution of the national total’ refers to the number of reports submitted by community pharmacists expressed as a percentage of total reports submitted by all sources to ADRAC. For example, the average annual percentage contribution by community pharmacists to the national total reported by ADRAC increased from an average 4.1% annually between 1999 to 2003 to 6.4% annually between 2004 to 2008 (Figure 2). The data for these values were reported in the May 2008 issue of i2P. 1

A more specific indicator of pharmacists’ contribution is the ‘percentage pharmacy contribution of primary care’ which refers to the number of reports submitted by pharmacists expressed as a percentage of total reports submitted by all primary care sources to ADRAC . The mean level of contribution compared with other health workers in primary care increased on average from 10.9% yearly in the five years between 1999 and 2003, to an average 23.3% yearly between 2004 and 2008 (Figure 2). 1 This represented an increase of 2.1-fold in the contribution by pharmacy from primary to ADRAC over the past 10 years.

Figure 2. Pharmacists’ contributions to adverse drug reactions reported to ADRAC 1999 to March 2008 : percentage of reports by sources in primary care and nationally.
(Source : ADRMU, April 2008).

In Australia, the spontaneous reporting of ADEs to ADRAC by health professionals or the pharmaceutical industry is analogous to the voluntary or mandatory reporting to other national pharmaco-vigilance agencies like the Food and Drug Administration (FDA) in the USA.3 Spontaneous reporting is appealing because it may lead to the identification and evaluation of rare drug-associated events in a range of circumstances including when therapeutic substances are used in combination with multiple other products. It may allow some comparisons of adverse events across drug classes.

It is not feasible however to determine the rate of a particular adverse event occurring in populations because of the lack of data on the numerator (number of cases) and the denominator (total number of people exposed). 3 That is, the incomplete reporting and reporting bias require caution in analyses of spontaneous reporting.

3.0 . Population health databases and quantifying adverse drug reactions
The belated recognition in 2004 of the adverse cardiovascular effects associated with rofexocib (Vioxx) challenged national bodies such as the FDA and ADRAC to improve their monitoring capabilities.4 Subsequent proposals have been made by expert groups in the USA and Australia to improve the performance of national monitoring of safety in each country mainly through the utilisation of existing population databases and technologies nationally and in jurisdictions.5,6

There is a growing number of medical record databases in the USA, Canada, Scotland , Holland and in Australia which have been utilised for retrospective analyses of drug-associated conditions.7 The FDA has contracted with four database groups to improve its ongoing monitoring of adverse effects of marketed drugs . 7 ADRAC has sponsored a variety of case control and other pharmaco-epidemiological research since the 1980s to quantify the association and the outcomes of adverse reactions in populations initiated by spontaneous reporting.8

The latest advances in utilising population databases in Australia were presented in the National Prescribing Services’ National Medicines Symposium 2008 held in Canberra from 14 to 16 May 2008. 9 The University of South Australia’s Dr Libby Roughead, in the School of Pharmacy , revealed a range of novel population-based research of drug-associated morbidity resulting from studies of a national electronic database of veterans health records managed by the Department of Veterans Affairs.

The University of Western Australia’s Dr David Preen, in the School of Population Health , presented research on the epidemiology of adverse drug effects in hospitals utilising linked databases in the state. 9 The retrieval of data from other linked databases extended research into community populations resulting in the characterisation of the use of psycho-stimulant agents for the management of ADHD. Western Australia has the equal highest per capita consumption of these agents in the world and by far the highest of any jurisdiction in Australia. Pharmacist researchers were involved in these studies.

A national, more systematic and ongoing approach involving pharmacists who worked with aged and paediatric patients has been proposed in the wake of the delayed recognition of the serious adverse effects resulting in the withdrawal of Vioxx in 2004. 10

4.0 Comparison of ADRAC and FDA monitoring in 2004.
In order to compare the safety monitoring performance of the Food and Drug Administration in the USA with ADRAC in Australia , the ADRAC data on numbers of adverse reactions reported in 2004 by drug company and non-company sources for 2004 were compared with corresponding data reported by the Food and Drug Administration in the USA.5

The FDA receives reports nationally through the MedWatch program which is the US equivalent of the ADRAC system in Australia.3 In the case of company reports to the FDA , the number of 89,960 “serious” adverse events was adopted (Table 1).5 The numbers of reports were standardised to rates by dividing the recorded numbers of reports by the populations in each country in 2004 (Table 1).

Compared with the rate of 72.1 reports per million people in the USA from non-company sources to the FDA’s MedWatch program , ADRAC had a 7.2-fold higher rate of 517 reports per million people (Table 1). The higher rate of reports to ADRAC by non-company sources compared with the FDA supports an earlier report of the effectiveness of ADRAC’s monitoring system compared with those operating in other developed countries. 8

The rate of 301.7 drug company reports of serious adverse events per million people in the USA to the FDA was 2.1-fold the rate of company reports to ADRAC in 2004 (Table 1). The 2.1-fold higher rate of company reports to the FDA compared to ADRAC suggest that there may be a relatively stronger requirement for the reporting of adverse drug events to the FDA by drug companies in the USA compared with Australia (Table 1). Alternatively, the much larger pharmaceutical industry in the USA with much higher numbers of companies and of drug products, together with the wider range of post-marketing surveillance studies, would result in a higher number of ADE reports altogether from pharmaceutical companies.

Table 1. ADR reports to FDA (USA)  and  ADRAC (Australia) in 2004 : numbers of adverse reactions reported by drug  company and non-company sources .
[Sources: Reference 5 and  ADRMU, 2008]

Source of reports

FDA reports in 2004

per 106 population

ADRAC reports in 2004

per 106 population

ADRAC Vs FDA comparison of reports per population 

Patient and provider (non-company )

72.1 /106

(21,493 reports /298.2  x 106 )


(10,458 reports/20.2 x 106 )

ADRAC had 7.2-fold reported rate of FDA



(89,960 reports /298.2 x 106 )


(2,909 reports/20.2
x106 )


FDA had 2.1–fold the reported rate of ADRAC

5.0 Conclusions
The following conclusions were drawn largely from an initial analysis of reports to ADRAC in Australia from 1999 to 2008 and from a comparison of reports received in 2004 by ADRAC and the FDA in order to assess their safety monitoring performance :
* In Australia, hospital pharmacists have continued to play a major role in the organisation of adverse reaction reports sent by hospitals to ADRAC from 1999 to 2008. This reinforced the historical importance of hospital pharmacists in reporting to ADRAC since it was established in 1970
* Community pharmacists in Australia substantially more than doubled the proportional contribution of reports made to ADRAC from primary care source in the period from 2004 to 2008 compared to 1999 to 2003
* When adverse reaction reports were standardised by the respective populations, ADRAC’s system of monitoring reactions from health providers and consumers appeared superior in 2004 to the FDA’s MedWatch program
* The rate of reports from US drug companies to the FDA was higher in 2004 than the rate of reports by companies in Australia to ADRAC. This difference may need to be explored with the objective of improving the rate of reports from pharmaceutical companies in Australia
* Population-based health databases internationally and in Australia are proving to be fertile research resources for quantifying the rate, geography and other characteristics of drug-associated morbidity. The FDA directly contracts with database groups to monitor adverse effects in populations in the USA . With the growing access to health databases in Australia, it may be timely for ADRAC to investigate the FDA’s actions and adapting these in Australia
* In Australia, research pharmacists have been active in quantifying drug-associated morbidity by analysing data retrospectively from national and linked Western Australian health databases. These databases create important opportunities for new research by schools of pharmacy nationwide
* Proposals for the prospective monitoring by pharmacist practitioners of adverse drug reactions in aged, paediatric and other sub-populations suggest the potential for a future role in community and hospital pharmacy.

Pharmacists in the 21st century, working in practice and research , have made important and hitherto under-estimated contributions to the national monitoring of adverse drug reactions in Australia. There is immediate potential for them to participate more in practice and research and contribute more to the better use of medicines in Australia.

The end
Con Berbatis
School of Pharmacy
Curtin University of Technology (Western Australia)
29 May 2008
Email: berbatis@git.com.au

1. Berbatis C. Primary care and pharmacy: 3. national adverse reaction reporting and pharmacists in Australia. i2P Issue 71:May 2008. Accessed at : http://i2P.com.au/?page=site/article&id=971 (28 May 2008 ).
2. Therapeutic Goods Administration. Guidelines on the reporting of adverse drug reactions by drug sponsors. Reviewed 9 November 2007. Accessed at : www.tga.gov.au/docs/html/adrguide.htm (29 May 2008).
3. Ahmad SR, Marks NS, Goetsch RA. Spontaneous reporting in the United States. In: Strom BL, Kimmel SE, eds. Textbook of pharmacoepidemiology. Fifth edition. Chichester (UK): John Wiley & Sons; 2006 : 91-116.
4. Berbatis C. Vioxx and other drug hazards challenge FDA, ADEC and ADRAC. i2P Issue 33 December 2004. Accessed Apr 26, 2008 at : http://i2P.com.au/?page=site/article&id=163
5. Institute of Medicine (US). Committee on the Assessment of the US Drug Safety System. Balciu A, Stratton K, Burke SP, eds. The future of drug safety : promoting and protecting the health of the public . Washington DC: National Academies Press, 2007.
6. Kelman CW, Pearson S, Day RO, Holman CDJ, Kliewer EV, Henry DA. Evaluating medicines : let’s use all the evidence. Med J Aust 2007; 1876: 249-252.
7. Morrato EH, Elias M, Gericke CA. Using population-based routine data for evidence-based health policy decisions : lessons from three examples of setting and evaluating national health policy in Australia, the UK and the USA. J Public Hlth 2007; 29: 463-470.
8. Boyd IW. The role of the Australian Adverse Drug Reactions Advisory Committee (ADRAC) in monitoring drug safety. Toxicology 2002; 181/182: 99-102.
9. National Prescribing Service. National Medicines Symposium 2008. Final Program and Abstract Book. Canberra 14-16 May 2008. Accessed 29 May 2008 at: http://www.nps.org.au/site.php?page=3&content=/resources/content/mediainfo_nms2008.html
10. Berbatis CG. Vioxx, Bextra and paediatric antidepressants. Aust Pharmacist 2004; 23: 741-743

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