The European Directive 2010/84/EU pledges pharmacovigilance on the front of the adverse events caused by therapeutic errors and inappropriate drug use: which opportunities arise and what critical points need to be solved yet?/p>
Since July 2012, the new legislation allows a better management of drug adverse effects, including in the detecting and reporting process all the adverse events that can occur during a pharmaceutical treatment, also the “preventable” ones, that are correlated to inappropriate drug use or therapeutic error.
Not all therapeutic errors cause damage to patients, but it is well known that an important part of harmful drug effects (estimated between 18.7% and 56% of all drug adverse reactions) is due to therapeutic errors.1 Preventable drug adverse reactions represent a serious problem for all healthcare systems, both for the damages caused to patients’ health and for the management costs at the expense of the healthcare systems.
The real dimension of therapeutic errors in the practice is very uncertain. Literature reports highly variable error rates, from 0.038 to 56.1 errors every 100 administrations; on average 5.7% of all drug treatments are affected by therapeutic error and about 6% of hospitalized patients are involved in a therapeutic error.2 Therapeutic errors can occur within any phase of the drug management process, especially in the administration phase (53% of all errors, range 9-90, 7%), whilst in the prescription phase the reported error rate is 16% (range 13-74%), 11% in the transcription phase (range 2-14%) and 13.5% in the preparation phase (range 7-23%).2
The World Health Organization estimates that in Europe the total cost of therapeutic errors oscillates between 4.5 and 21.8 billion euros,3 whilst a recent report by the IMS Institute in the United States estimates that the cost generated by inappropriate drug use and therapeutic errors exceeded, in 2012, 200 billion dollars.4
The management of adverse events caused by therapeutic error requires a new cultural and methodology approach, centred on patient safety and safe and effective drug use.
The focus moves from drug safety evaluation to evaluating the safety of patients exposed to the drug. A unified vision needs to be developed, that embraces the traditional evaluation of safety profiles of medical products – mostly directed to regulators – but considers also the whole therapeutic process, within the clinical and organizational contest, to promote interventions aimed at improving patient safety. It is therefore necessary to combine knowledge and expertise, methods and instruments of pharmacovigilance with those typical of clinical risk management: only the real integration between the two systems will avoid wasteful, duplicate or partial and ineffective interventions. This new approach finds its roots in the Manifesto di Erice 2007, where patient safety was identified as the most important challenge for pharmacovigilance.5 That acknowledgment laid the foundation for the cooperation between the World Alliance for Patient Safety and the WHO Collaborating Centre for International Drug Monitoring, therefore opening a new perspective. A pilot project has been developed from this new cooperation and its first step has been a survey for evaluating how therapeutic error can be handled by pharmacovigilance centres.6 The questionnaire, sent in March 2007 to 88 Countries via Vigimed, collected the responses from 21 centres (23.8%). Fifteen stated that they were already active on the front of therapeutic error, working in collaboration with the Patient Safety Program (10 centres) or without it (5 centres).6,7
On much smaller scale, in July 2013 the Centre for Pharmacovigilance of Lombardy Region conducted a similar survey in order to evaluate the level of cooperation between the local pharmacovigilance supervisor and the risk management unit within the Local Health Services (ASL) and public or private accredited hospitals (AO). A questionnaire (table 1) was sent to 73 Centres (15 ASL, 20 AO, 1 Regional Emergency Service (AREU) and 28 other healthcare centres). In response, 64 filled questionnaires were sent back (88%): from the collected data emerges that around 50% of the centres declare to have a defined integration program, but only 23% defines it effective and satisfactory. Please see tables 2 and 3 for more detailed information on the answers.
Table 1 - Questionnaire for evaluating the level of integration between risk management and pharmacovigilance activities
|1. Does you centre participate to active pharmacovigilance projects?||No, it doesn’t|
|I don’t know|
|Yes, it does (please state which ones)|
|2. Does a planned and “structured” coordination between risk management and pharmacovigilance activities exist yet||No, it doesn’t|
|Yes, it does|
|3. If you answered “Yes” at question 2, in short, how is it organized?||Open answer|
|4. Are you satisfied? Do you think it is effective?||Open answer|
|5. Do you have any suggestion on the organizational level?||Open answer|
Table 2 - Amount of sent questionnaires and received responses on participation to active pharmacovigilance projects
|Centres||Sent questionnaires||Compiled questionnaires||Centres that participates to active pharmacovigilance projects||Amount of active pharmacovigilance projects per centre|
|ASL||15||15 (100%)||14/15 (93%)||1-3|
|AO||29||29 (100%)||29/29 (100%)||1-6|
Private accredited bodies
|28||19 (68%)||7/19 (37%)||1-4|
|Total||73||64 (88%)||50/62 (81%)|
Table 3 - Integration between risk management and pharmacovigilance activities
|Centres||Integration between risk management and pharmacovigilance|
Effectiveness and satisfaction level
Private accredited bodies
|Total||30/64 (47%)||15/64 (23%)||13/64 (20%)||6/64 (9%)|
A new path has been opened that will strongly involve resources and expertise of pharmacovigilance and risk management for overcoming the present problems:
- events detection, on which under-reporting lies heavily, that penalises both pharmacovigilance and risk management, even though for different reasons;
- coexistence of separate and not-compatible databases (“incident reporting” used by the risk management system and reporting system by pharmacovigilance);
- presence in literature of several definition of drug adverse reaction, preventable drug adverse reaction, medical error… that can create confusion and prevent epidemiological studies to be compared;
- different methods used for the evaluation of “preventability” and for the event classification; besides, only a clear and homogeneous definition and classification of the events can allow their correct analysis, the understanding of their causes and therefore effective actions for their prevention;
- quality and completeness of information: unfortunately the frequent poor quality in compiling the reporting forms, which are often incomplete or not very accurate, prevents the event analysis and the understanding of the issue;
- management of near misses (“near miss” is defined as “error and potential cause of adverse event that does not occur for fortunate circumstances whether because it is discovered in time or because it does not cause adverse consequences on the patient”8). The new European legislation does not require near miss reporting, which however are indicators of insufficiency in the system, organization or staff training that allowed the error to take place: they represent then an informative patrimony that must not been wasted, but managed.
For sure a long path of hard work is opening in front of us, but also a great opportunity: the creation of a system that can assess drug safety with a much wider perspective, providing multi-level interventions finalised to safe and appropriate drug use, risk reduction and error prevention.
1 Regional Centre of Pharmacovigilance, Lombardy Region
2 Specialization School in Medical Pharmacology, University of Milan