Medicines information: making better decisions

In the UK, the National Health Service (NHS) strives for equality of care whilst working with a limited budget, explained Amanda Adler (Consultant Physician, Institute of Metabolic Sciences, Addenbrookes Hospital, Cambridge and Chair, Technology Appraisal Committee B, National Institute for Health and Care Excellence (NICE), UK). NICE and the Scottish Medicines Consortium (SMC) consider how well a new medicine works compared with existing products and whether it represents good value for money.

In doing this they consider both the manufacturer’s submission and an academic assessment. Cost is critical because money spent on one drug  is not then available for others. When comparing a new product with the standard reference product, NICE uses the generic measure of the effectiveness – the quality adjusted life year (QALY) and the incremental cost-effectiveness ratio (ICER) or cost per QALY, which is the difference in costs divided by the difference in QALYs. NICE evaluations are always from the NHS perspective and for the patient’s lifetime.  In practice, a technology that costs less than £20,000 per QALY is likely to be accepted and one that costs more than £30,000 is likely to be rejected.

Technology appraisal committees need to be vigilant and critical because sometimes trial data can be misleading. For example, an inappropriate endpoint might have been used or a trial might have been stopped early because the effects appeared to be better than they really were or the company may have failed to follow good statistical practice, said Dr Adler. New technologies are often more effective and more costly but occasionally a medicine that is marginally less effective and much cheaper can be a cost-effective option for the NHS. Another interesting challenge is the situation where a drug provided free-of-charge is not cost-effective because of elaborate monitoring requirements. In spite of the challenges, NICE says ‘yes’ more often than it says ‘no’, concluded Dr Adler.

Making a good decision about treatment for an individual patient involves a combination of current best evidence and clinical expertise with consideration of the patient’s concerns, Barbara Claus (Ghent University, Faculty of Pharmaceutical Sciences, Belgium) told the audience. In practice, feasibility is an important consideration; health systems need to know if a treatment works and provides value for money. The willingness-to-pay (WTP) threshold is usually set at €35,000 per annum in Belgium.

Patient preferences must be considered when evaluating the burden of taking medicines regularly to prevent adverse events in future. One study showed that more than 8% of patients were willing to die two years earlier rather than take a daily pill and a further 21% were willing to trade between one week and one year (for not having to take a daily pill), she said.

Reluctance to take regular medication can lead to sub-optimal adherence and this can have a significant effect on the outcomes of some treatments. It is important to be aware of the ‘adherence gap’. When taking new oral anticoagulants (NOACs) one extra dose increases the risk of bleeding; missed doses increase risk of clotting. The modelling of statin usage for prevention of cardiovascular disease assumes complete adherence to treatment; a 10% reduction could lead to a loss of effectiveness and, in this case, could cost €80 million in Belgium. In practice, pharmacists need to take these types of factors into account, said Dr Claus.

Implementation science helps researchers and clinical pharmacists to understand which services are likely to be most effective and how they should operate for maximum benefit, according to Karen Farris (Professor of Pharmacy Administration, University of Michigan College of Pharmacy,USA ). Systematic reviews of studies focus on outcomes e.g. studies of pharmacist-led management of blood pressure show that reductions in systolic blood pressure are consistently achieved. However, study conditions may not reflect the real-life situation, she said.

Two frameworks have been devised to assess implementation outcomes; they are the Consolidated Framework for Implementation Research (CFIR) and RE-AIM. RE-AIM considers five elements of implementation – Reach, Effectiveness, Adoption, Implementation and Maintenance. These can be used to help plan the translation of research-based services into routine, day-to-day practice. This can be done when there is already good evidence of pharmacists’ contribution to positive outcomes e.g. areas such as hypertension, diabetes, hyperlipidaemia, she suggested.

When considering implementation of a service, sustainability is critical; “you have to work with what you’ve got”, said Professor Farris. “If physicians are resistant, stay away from them; identify physician champions and work with them – they will spread the word. Start with the ones who want to work with you – there will always be at least one”, she said.

The European Medicines Agency (EMA) has had a pioneering role in collaborating with patients and consumers to refine its communications and a particular area of interest has been the benefit to risk profiles of medicines, according to Bruno Sepodes (Chair, Committee on Orphan Medicinal Products, EMA). Information on benefit to risk profiles contributes to the safe and effective use of medicines and is now an intrinsic element of the regulatory process. Good communications are evidence-based, unbiased, timely, up-to-date and adapted to the needs of the target audience.

The EMA holds benefit to risk information on the medicines that are authorised centrally but not those authorised via decentralised or national procedures. It also communicates information on emerging safety issues. A variety of routes is used for communication including web-based platforms, direct healthcare professional communications, press releases and documents in lay language for patients.  At the time of authorisation of a medicine the European public assessment report (EPAR) and a risk management plan (RMP) are published.

Written in lay language, the EPAR includes an explanation of why the medicine was approved and why its benefit/risk profile is positive. The RMP is aimed primarily at stakeholders with a professional interest in medicines. After authorisation the Pharmacovigilance Risk Assessment Committee (PRAC) monitors and publishes emerging safety information. For example, in 2013, the risk of venous thromboembolism with combined hormonal contraceptives was reviewed and the final decision (that the benefits continue to outweigh the risks) was published.

One of the most important features of the EMA is the way in which it works with patients, for example, to review EPAR summaries and package leaflets. Many documents have been refined and clarified as a result of the input from patient reviewers, noted Dr Sepodes.

Official medicines’ information sources vary in their usefulness and, paradoxically, the Food and Drug Administration (FDA) website is not very useful for current label information but good for regulatory history and approval information, Gerald McEvoy (Assistant Vice President, Drug information, ASHP) told the audience. Moreover, there can be a certain amount of redacted information in an FDA review because manufacturers are allowed to do this, he added.

Structured product labelling (SPL), originally developed to support health information management technology, has now become the norm. It is the format used by DailyMed, which is the best source of up-to-date information about current labelling of medicines, said Dr McEvoy. DailyMed is maintained by the National Library of Medicine (NLM) and is publicly accessible.

Pillbox, which enables searches of solid oral dosage forms for identification, also  links to DailyMed labelling and the NLM Drug Information portal, but is still under development.  Medwatch, the FDA safety information and adverse event reporting programme, provides important safety alerts and summaries in addition to its reporting facility.   Finally, the ASHP Drug Shortages website provides comprehensive information on drug shortages including guidelines, resources and information about alternative products.

Clinical decision support systems (CDSSs) built into electronic prescribing systems are generally assumed to make prescribing safer but many systems have been developed and the results are not always as good as expected, according to Hanna Seidling (University of Heidelberg, Department of Clinical Pharmacology and Pharmacoepidemiology, Germany). They provide alerts and information but rely on action by the prescriber. Health care professionals want systems to be easy, to help them when prescribing unfamiliar drugs, a reference source and “to know when I need it”, said Dr Seidling. Ideally, alerts should be pertinent to the actual patient and the level of knowledge of the prescriber.

In fact, most current systems display alerts for all known theoretical risks associated with the drug and ‘alert fatigue’ quickly becomes a problem. Links to patient data could help to refine the alerts and analysis of over-ridden alerts could help in further adaptation of the system. Further development may be needed to make CDSS more user-friendly; research shows that every consultation between a physician and patient comprises four steps – problem formulation, treatment negotiation, reaching agreement and instructing the patient.

The first three steps take up most time and only after that does the physician key in the prescription. Receiving warnings and suggestions at this stage when time has already been invested in reaching a decision is problematic and there is a tendency not to want to change, explained Dr Seidling.

The inclusion of advice for patients was an important predictor of success with CDSS according to one study, noted Dr Seidling.  However, there are so many different systems targeting different aspects of medication process that it is difficult to compare them meaningfully, at present. Well-designed systems reduce the risk of harm to patients but further work is required to evaluate effectiveness, she concluded.

Health expenditure is not a cost to be contained but a crucial investment to promote economic growth, argued Ana Nogueira (Medical Director, MSD, Portugal).  Furthermore, between 1986 and 2000 life expectancy in 52 countries increased by almost two years and it is estimated that about 40% of that increase could be attributed to the introduction of new chemical entities.

Failure to use treatments correctly can be more expensive in the long run because it risks incurring both the costs of the drugs and the cost of the untreated or poorly treated disease, she explained. This is a problem that will grow as life expectancy increases, she added.

Another important development is personalised healthcare, an approach that is associated with improved health outcomes. At present healthcare systems are largely impersonal and what is needed is a patient-centred model which pays for desirable outcomes rather than merely reimbursing costs. A critical element of this will be improving communication with patients. Patients do not always understand what they are told and there is a tendency for health care professionals to give too much information. There is a case for ‘rational use of information’; “too much can be counter-productive”, said Dr Nogueira.  In addition, new communication methods will be needed, for example, electronic reminders to prompt patients to take medicines.

In Portugal health care professionals are not permitted to use brand names when talking to patients about their medicines because this is considered to be tantamount to promotion. Dr Nogueira suggested that this might be a step too far.

There is an inherent conflict of interest between the legitimate business goals of manufacturers and the social, medical and economic needs of providers and the public, Tim Reed (Executive Director, Health Action International, Amsterdam, The Netherlands) told the audience. On occasions manufacturers have been accused of disease-mongering or promoting treatments for non-diseases such as short-eyelash syndrome or double chins, he continued.

When asked  whether promotion affected prescribing the majority of internal medicine residents said it had little, if any, effect on them but 50% believed that it significantly affected other physicians’ prescribing. There is no doubt that promotional activities, including advertising in professional journals, medical education activities or disease awareness campaigns, are effective in increasing prescribing. At present pharmaceutical companies spend 25% of marketing budgets on digital marketing and this marks a shift away from health professionals towards the patient as the customer, argued Dr Reed.

EU regulation of promotion falls short in a number of respects and self-regulation by the pharmaceutical industry has proved to be weak; fines for breaches of regulations amounted to 0.0051% of annual sales revenue in the UK, he said. What is needed is sound regulation with punitive fines for breaches, education about pharmaceutical promotion in the medical curriculum and mandatory disclosure of interactions between the pharmaceutical industry and health professionals.

The separation between advertising and information could best be achieved by legislation to ensure that information was provided by central Government according to Dr Reed whereas Dr Nogueira argued against a paternalistic approach, saying that consensus would be preferable.