Reporting Adverse Drug Reactions: A guide for healthcare professionals
May 2006
Introduction
According to information published by the Medicines and Healthcare products Regulatory Agency (MHRA) ‘an adverse drug reaction (ADR) is an unwanted or harmful reaction experienced following the administration of a drug or combination of drugs, and is suspected to be related to the drug. The reaction may be a known side effect of the drug or it may be new and previously unrecognised’ (see reference 4). This is opposed to an adverse event which ‘is any undesirable experience that has happened to the patient while taking a drug but may or may not be related to the drug’ (see reference 4).
In the British National Formulary (BNF) it is noted that an ADR can be caused by any therapeutic agent, including prescribed and OTC drugs, blood products, vaccines, radiographic contrast media and herbal products, and that all of these should be reported (see reference 5).
If an unexpected reaction is observed in a patient it may be difficult to establish its causality and thus if it has resulted from the administration of a drug or combination of drugs. Guidance on factors that should be considered when trying to establish causality of a reaction is provided by the MHRA on their website at www.mhra.gov.uk (see reference 6). The resource notes that it is important to consider the nature of the reaction, the timing of the reaction in relation to drug administration, the relationship to the dose administered and other possible causes of the reaction including concomitant medications and the patient’s underlying disease.
Further information on the different types of ADRs that occur and on identification of ADRs can be found in guidance for healthcare professionals produced jointly by the Department of Health (DH) and the NHS on their PRODIGY guidance website at www.prodigy.nhs.uk (see reference 7). For information about allergic reactions to medications, an important type of ADR, refer to the British Society of Allergy and Clinical Immunology which works to improve the management of allergic and related disease, at www.bsaci.org. A clinical review published in the BMJ offers a good summary of the importance and types of ADRs that can be experienced (see reference 8).
The prevalence of ADRs
Adverse reactions are more common than might be expected and there can never be a guarantee that a medicine is completely safe. Determining the precise number of ADRs that are experienced, however, is virtually impossible given the difficulties in assessing causality and the low proportion of ADRs that are reported. ADRs also vary in their severity, by what type of medication they are caused and in what setting they are experienced, making identification complex.
Most research which has tried to quantify ADRs has done so by evaluating hospital patients and admissions in particular. A study of hospital admissions in the UK, published in 2004, found that 6.5 per cent of people admitted to hospital had experienced an ADR and that in 80 per cent of those, the ADR was the direct cause of the admission (see reference 9). This research (which excluded admissions due to drug overdose) also found that ADRs accounted for 4 per cent of hospital bed capacity and resulted in a projected annual cost to the NHS of £466 million.
The 1998 study also found that over 2 per cent of those patients who were admitted to hospital with an ADR died. This would make the overall fatality rate from ADRs within the population 0.15 per cent. Similar results were found by a meta-analysis of ADRs in hospitalised patients in the USA. This study found overall incidence of serious ADRs (on admission and experienced while in hospital) to be 6.7 per cent and of fatal ADRs to be 0.32 per cent (see reference 10).
Preliminary data from an ongoing contemporary study at the Royal Liverpool University Hospital has indicated that about 16 per cent of patients suffer an ADR as hospital inpatients (see reference 11). Many ADRs are experienced by patients when they are being treated in primary care or as outpatients. It is difficult to quantify the actual prevalence of ADRs and there has been little research into the incidence of ADRs in patients treated in primary care.
One small study in the USA found that around 25 per cent of outpatients had experienced an ADR and that in many instances they were preventable or ameliorable (see reference 12). Given the small amount of data, more research should be done into the incidence of ADRs outside secondary care.
What is pharmacovigilance?
During clinical trials, while there are a number of different test phases (see appendix A), only a small number of patients are exposed to a medication, over a limited period of time, compared to the number that might use it once it is licensed, ie once a marketing authorisation has been granted. Rare adverse reactions, occurring in only a small percentage of cases, after a long period of use or when a drug interacts with a particular combination of other medications or conditions, may not be detected during clinical trials.
Pharmacovigilance is the ‘science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem (see reference 13). If ADRs that are not discovered during clinical trials are to be detected, investigated and communicated, and the appropriate action taken, then it is vital that post-marketing pharmacovigilance of all medicines is comprehensive. Effective pharmacovigilance should take into account trends in use, as well as the occurrence of ADRs, enabling more effective advice to be given to those prescribing and using medications and should ensure better standards of safety and efficacy.
There are many different ways in which information can be collected and used for pharmacovigilance. These include the use of data from clinical and epidemiological studies, published medical literature, and information from pharmaceutical companies, morbidity and mortality databases, longitudinal patient databases and spontaneous reporting schemes. This report considers ways in which healthcare practitioners can contribute to the collection of pharmacovigilance data and therefore the focus will be spontaneous reporting of suspected ADRs and longitudinal patient databases.