More than 500 pharmacists from 52 countries attended the European Society of Clinical Pharmacy Symposium held in Prague, Czech Republic in October 2013. Key topics included models of practice, non-adherence and the placebo response
Christine Clark PhD FRPharmS FCPP(Hon)
In a session devoted to psychosocial and behavioural factors that influence effective use of medicines, speakers explored aspects of compliance, adherence and the placebo effect.
The process of patient care that follows the sequence, ‘examination, diagnosis, prescribing and adherence’ exists only in doctors’ imaginations because in real life patients often take medicines intermittently or not at all, explained Przemyslaw Kardas (Professor of Family Medicine, Medical University of Lodz, Poland).
The Ascertaining Barriers to Compliance (ABC) project is a collaborative project involving Poland, The UK, The Netherlands and Switzerland. It was designed to produce evidence-based recommendations for European policy-makers for improved patient adherence and subsequent better use of medicines in order to develop safer, more effective and cost-effective use of medicines in Europe.
There are currently large gaps in our understanding of adherence. For example, a recent systematic review showed that most factors so far identified are determinants of implementation (that is, taking the medicine according to the prescribed schedule) rather than determinants of persistence (that is, taking the medicine for the required period). The reviewers concluded that non-adherence behaviour is a complex phenomenon.
A survey of patients taking long-term antihypertensive treatment who were prescribed a short course of antibiotics showed that, overall, 48% and 21% were non-adherent to long-term and short-term treatment respectively. As these were not the same patients there was no correlation between the two findings, said Professor Kardas. A systematic review of studies to improve adherence showed that the only method that reached statistical significance was electronically-monitored feedback, although behavioural counselling was nearly significant, noted Professor Kardas.
Given that persistence with long-term treatment is generally poor and the cost of non-adherence is high, training of healthcare professionals to manage non-adherence is critical. A survey of European nursing, medicine and pharmacy training programmes showed that on average students received three hours of classroom training and two hours of practical training on this topic. Pharmacists are poor at asking patients about adherence according to a study that showed they rarely asked patients about missed doses, he added.
In conclusion, he said that there is an urgent need to create an ‘adherence-supporting environment’ and that adherence management represents an important opportunity for collaborative work between doctors and pharmacists.
The worldwide cost of non-adherence is estimated to be $285 billion, according to Bart van den Bemt (Departments of Pharmacy and Rheumatology, Sint Maartenskliniek, Nijmegen, The Netherlands). Many patients fail to persist in taking important treatments such as bisphosphonates or gastroprotective proton pump inhibitors in spite of increased risks of serious clinical consequences, he explained.
Non-adherence is a complex phenomenon. For some patients the barriers are practical, such as difficulty opening containers or lack of information; such problems can lead to unintentional non-adherence. For other patients, lifestyle and beliefs about medicines are barriers to adherence and such patients can be intentionally non-adherent. Patients evaluate the necessity for a medicine against their concerns about it, such as the risk of dependency or long-term side effects.
Turning to measures to improve adherence Dr van Den Bemt said that the patient needs to accept that he has a disease and that treatment is required. Without acceptance that ‘necessity’ outweighs ‘concerns’, the patient will not be willing to take the treatment, he emphasised. After this point, the main barriers are practical, such as forgetfulness. One way to overcome this is to use electronic reminders. For example, a recent review has shown that SMS reminders are effective in improving adherence in asthma patients.
Tackling intentional non-adherence calls for concordance skills based on motivational interviewing and cognitive behavioural approaches. Dr van den Bemt suggested that a discussion with a patient should include an exploration of perceptions of necessity and concerns about medicines and include open questions, non-judgmental reflections and reflective listening. It should also emphasise personal choice and the pharmacist should seek permission to educate the patient.
Most people want shared decision-making about their treatment, he said, and this calls for a set of competencies in communicating with patients about medicines and in managing and supporting medication adherence. Communication competencies include listening, communicating – that is, helping patients to interpret information in a way that is meaningful to them – and having up-to-date knowledge. The competencies required to manage and support adherence include understanding, exploring, deciding and supporting skills.
The placebo reponse
The placebo response is a useful model for understanding brain function, said Fabrizio Benedetti (Professor of Neurophysiology and Human Physiology, University of Turin, Italy).
Placebo responses have been observed in many situations including both medical and surgical interventions. The placebo response is complex and can involve many factors including psychobiological factors. The administration of a drug takes place in a complex psychosocial context and the sensory and social stimuli provided by the rituals of the therapeutic act tell the patient’s brain that therapy is occurring. In some situations, shamanic rituals do not differ greatly from those of conventional medicine, commented Professor Benedetti. Interestingly, the rituals activate the same pathways as drugs and this area has been well-studied in the area of pain.
For example, for patients who have previously been exposed to opioids or non-steroidal anti-inflammatory agents, the administration of a placebo (with the expectation of pain relief) activates the μ-receptor pathways and the CB1 receptor pathways through which opioids and NSAIDs, respectively, work. Even after surgery good pain relief is obtained in some patients when placebos are administered with positive verbal suggestions. During the expectation phase there is a reduction in pain intensity. When a positive benefit is expected, the descending pain modulatory network is activated and the net result is a reduction in pain perception. Thus, expectation can produce a real effect, said Professor Benedetti. On the other hand, if a negative suggestion is given – the so-called ‘nocebo’ effect – then pain intensity is increased. In this case there is deactivation of the relevant receptors. Pain is not a special case – placebo responses have also been found in patients with Parkinson’s disease, he added.
There are both placebo responders and non-responders and at least two mechanisms are involved. The first is learning or positive conditioning. If a patient is given a placebo after repeated administration of a real analgesic then a bigger (positive) response is elicited than with verbal suggestion alone. The second mechanism is genetic in origin. Genetic variations leading to placebo responder or non-responder status have been identified for a number of conditions including irritable bowel syndrome and major depressive disorder. Obviously it is very important for drug manufacturers to be aware of genetically-determined effects so that appropriate patients can be selected for clinical trials, commented Professor Benedetti.
Another question that had arisen was whether the action of a drug was the same without the psychosocial context and therapeutic rituals. Studies have shown that ‘hidden’ administration (that is, when the patient is not expecting to receive a dose of a drug) is less effective than open administration of buprenorphine, tramadol, ketorolac and metamizol. Moreover, a comparison of open and hidden metamizol in post-thymectomy pain showed that there was virtually no reduction in pain intensity with hidden metamizol. This suggests that the therapeutic effect of metamizol (openly-administered) is entirely due the placebo response. For an opioid, such as morphine, there is no difference between hidden and open administration, noted Professor Benedetti.
Models of practice
Medicines management review has a positive impact on the quality use of medicines, for example, a reduction in the use of sedatives in elderly patients in care homes, according to Timothy Chen (Associate Professor of Pharmacy, University of Sydney, Australia). Medication review will be come increasingly important as the population ages. In 2000 the proportion of the world’s population over 60 years of age was 18% but by 2050 it is expected to be 40%. Furthermore, current statistics show that more than 50% of the over-65s have five or more comorbidities. This group also has a correspondingly high use of medicines – 41% of over-75s in Australia are taking more than four medicines each day, said Professor Chen. This is important because it increases the chances of drug-related problems, which impose a considerable economic burden, he commented. Many such problems are preventable, but this requires a paradigm shift for community pharmacy.
Community pharmacy services have traditionally been focussed on rapid dispensing of medicines but the focus is now shifting to medication review services for the patient. The purpose of this is to achieve the quality use of medicines – that is the judicious, appropriate, safe and efficacious use of medicines. Two types of service have been developed in Australia, namely, residential medicines management review (RMMR) and home medicines review (HMR). Both services are reimbursed by the Australian government. A meta-analysis of studies of medication reviews and educational interventions performed as part an RMMR project showed that the use of hypnotic medicines was reduced although the use of antipsychotic medicines was not.
HMR involves the referral of a patient by GP to a community pharmacist, who then visits the patient at home and reviews all the medicines. The pharmacist provides the GP with a report and recommendations and the GP and patient agree on a medication plan. This final step is essential for payment for the GP, noted Professor Chen. Research into HMR services has yielded some interesting results. One study examined 224 HMRs to determine the proportion of recommendations made by pharmacists that were evidence-based. The results showed that 1100 drug-related problems were identified leading to 964 recommendations, of which 94% were supported by current guidelines. Other studies examined the drug burden index (DBI) before and after medication reviews by pharmacists. The DBI is based on the numbers of anticholinergic and sedative drugs in a patient’s regimen and reflects the functional burden of medications. Two studies showed that DBI was decreased. Finally, one study had investigated the impact of HMR on medication appropriateness. The results showed that there were large and significant differences after HMRs performed by pharmacists. Professor Chen concluded that medication review by pharmacists has a positive impact on quality use of medicines.
Clinical pharmacy practice at level 3 and level 4 has been investigated in several European countries. Level 3 is defined as the provision of reactive advice, for example, where prescription interventions are made after prescriptions have been written. Level 4 involves the prospective provision of advice, for example, participation in the decision to prescribe or modify a prescription and/or referrals by other professionals, explained Anne Spinewine (Professor of Pharmacy, Catholic University of Louvain, Belgium). There is, as yet, no systematic review describing European data on studies of level 3 and level 4 activities. However there are a number of individual studies that mostly show high levels of acceptance of pharmacist’s recommendations. A small number of randomised controlled trials also demonstrate positive benefits such as reduced readmissions and emergency department visits. One study in London had compared level 3 and level 4 activities and shown a lower increase in medication costs as a result of level 4 activities.
A survey conducted by the European Association of Hospital Pharmacists in 2010 had shown that only 6% of pharmacists spent at least 50% of their time on wards and 40% of pharmacists were reported to offer clinical services ‘occasionally’. In addition, the number of pharmacists per 100 beds ranged from 0.24 (in Bosnia and Herzegovina) to 4.35 (in the UK) and only 14.7% of pharmacists recorded their interventions in the patient’s medical record.
Several European countries have articulated a vision for pharmacy practice and set out explicit standards. Professor Spinewine suggested that it would be important to move forwards in a stepwise fashion with documentation, benchmarking and evaluation at each stage. The planned European summit on hospital pharmacy in 2014 will provide an opportunity to set out the future direction of the profession and define the ways in which pharmacists can serve patients and collaborate with other healthcare professionals, she concluded.
Hospital pharmacy services have developed and changed over the past 50 years and some have disappeared altogether, said Barry Carter (Professor of Pharmacy Practice and Science, University of Iowa, USA). For example, Drug Information Centres no longer exist because pharmacists now find drug information via their tablet computers or mobile phones, he continued.
Recently, pharmacists have become more involved in family medicine where their role is to design treatment regimens, optimise medicines and educate patients. One example of work in this area is two randomised, controlled trials to evaluate the impact of a pharmacy intervention to optimise medicines and improve blood pressure control. The results showed that the intervention groups achieved significantly better control of blood pressure over the nine-month study period and that this was sustained for a further 24 months.
Turning to future directions for pharmacy services Professor Carter said that at the University of Iowa Hospital there are 250 pharmacists of whom 50 are clinical pharmacists. About 50% of the pharmacists spend their time preparing intravenous additives, dispensing unit doses at ward level and checking the work of technicians. The pharmacy operates a 24-hour service. In order to be appointed as a clinical pharmacist, an individual must first complete additional training (residency training) in the specialty area and obtain certification from the Board of Pharmacy Specialties. Currently, Board certification is available in six specialties – ambulatory care, nuclear medicines, nutritional support, oncology, pharmacotherapy and psychiatry. Some 16,000 pharmacists are now certified to practise in pharmacotherapy, he added.
Clinical pharmacy in hospitals
Medication errors are an international problem. There is a need to optimise medicines at the patient level but pharmacists must also use their expertise to support safety at the system level too, said Jeannell Mansur (Practice Leader, Medication Safety Joint Commission International, USA). Describing the work of the Joint Commission International (JCI), she said the organisation’s mission is to improve safety and the quality of patient care. It offers a route for accreditation for healthcare organisations outside the US. It has so far accredited more than 500 organisations, including 10 in the European Union. JCI is recognised for having predominantly patient-centred standards and achievable goals.
“Too often our leaders do not recognise medication safety as a strategic priority until a disaster hits the headlines”, she said. High-alert, high-risk medicines deserve special attention and measures need to go beyond simply putting a ’high-alert’ label on such products; each high-alert medicine poses a different risk and warrants an individual approach, for example, chemotherapeutic agents differ from concentrated potassium chloride. Sterile admixtures are another area of concern and the JCI is now forbidding preparation of intravenous doses outside the pharmacy unless the dose is needed urgently or the product has a short expiry time. Professor Mansur advised the audience to stay abreast of leading practices, establish robust error-reporting schemes, plan developments carefully on the basis of thorough analysis and educate and train staff well on medication safety processes.
Screening to identify patients at risk of drug-related problems (DRPs) and adverse drug reactions (ADR) is critical, said Mirko Petrovic (Department of Geriatrics, Ghent University Hospital, Belgium). One method that has been developed is the GerontoNet ADR risk score. This takes into account a number of factors of which the most important (and therefore the most heavily weighted) are the number of medicines and a history of previous ADRs. GerontoNet has a maximum possible score of 10, but a patient scoring 4 is already at risk, noted Professor Petrovic. So far, GerontoNet has only been validated for hospital inpatients and further work has to be done for other groups, he added.
Medication review should involve a structured, individualised assessment by a clinical pharmacist with full access to the medical file, in order to identify DRPs. The process should include identification of all the medications that the patient is taking, screening for misuse, underuse or overuse of drugs and formulation of possible solutions to DRPs for discussion with the treating physician and, if possible, with the patient, said Professor Petrovic.
A number of tools have been developed to help to identify inappropriate prescribing in the elderly. The Beers criteria identify drugs that pose greater risks in the elderly, the STOPP criteria identify inappropriate drugs in the elderly and the START criteria identify the right drugs for elderly patients. These measures, which are focused on drugs and based on explicit criteria, do not tell the whole story, explained Professor Petrovic. The medication appropriateness index (MAI) is a judgement-based measure that is focused on the patient. It involves asking 10 questions about each drug, although a modified 8-question version has been developed in Belgium. The MAI is time-consuming to administer and requires knowledge but it is a reliable instrument with good agreement between pharmacists’ and geriatricians’ scores.
Computerised prescribing systems can also be used to screen for inappropriate prescribing but very few studies have demonstrated improvements in patient outcomes and the existing systems are not geriatric-specific.
Comprehensive geriatric assessment (CGA), which takes into account all the healthcare problems of an individual, may be the best way forward. In fact, CGA associated with a multidisciplinary team approach, compared with usual care in frail older adults shows a 35% reduction in the risk of a serious ADRs and a substantial reduction in unnecessary and inappropriate drug use, commented Professor Petrovic.
None of the existing approaches shows a clear beneficial effect on patients’ health outcomes if applied in isolation and future developments are likely to involve combinations of methods, he predicted. In future, the desirable model of care in acute settings would include a medication history on admission, medication review and individualised patient counselling during hospital stay, the provision of discharge information/education for patients and health care professionals and follow-up telephone calls, he concluded.
Clinical pharmacy services should be defined, listed, visualised, documented, published and evaluated, Annemie Somers (Senior Pharmacist, Ghent University Hospital, Belgium) told the audience. Describing the pharmacy services at the University Hospital of Ghent, she explained that 14 pharmacists deliver pharmaceutical care to a total of 1060 beds. Their duties include rounding with physicians, making interventions, medicines reconciliation and antibiotic stewardship.
Medicines reconciliation is an important activity for which the hospital has received additional funding. Drug histories are taken in the Emergency Department by pharmacy technicians who are “even better than pharmacists” at this job, she said. The histories are recorded electronically and then reviewed by a clinical pharmacist. Patients’ allergies and pharmacists’ recommendations are also recorded electronically. A spin-off from this project has been training of nurses to take drug histories and the preparation of an aide mémoire to help them. The final step in the process for elderly patients is the ‘Home Medication Bag’, comprising discharge medicines and a list detailing the medicines, the doses and useful information such as the names and contact numbers of the patient’s family doctor and community pharmacist. Other projects included medication reviews for elderly patients and surgical patients and monitoring of oral chemotherapy.
The hospital has recently switched to the Qmentum hospital accreditation system that contains 22 standards for managing medicines. Some of these are very relevant to clinical pharmacy, noted Dr Somers. In connection with the accreditation process, pharmacists have been working on several projects including descriptions of the work that clinical pharmacists undertake, the development of key performance indicators, service level agreements and medication safety plans. The first audit identified a number of points for improvement. For example, it was found that there was no clear back-up system for clinical pharmacy services, not all pharmacists recorded their recommendations in the patient’s record and physicians were not obliged to respond to a pharmacist’s recommendation. Dr Somers concluded that documentation of pharmacy recommendations is essential and that standardised methods and tools should be used wherever possible.