Clinical Pharmacology and Therapeutics. Группа авторов
Pharmacovigilance
There is now a greatly increased obligation on pharmaceutical companies to set up risk‐management plans. In Europe, the EMA launched EudraVigilance in 2017 which is a system for managing and analysing suspected adverse reactions to medicines that have been authorised or are being studied in clinical trials. The aim is to support safe and effective use of medicines by sharing safety reports across Europe, allowing early detection and evaluation of safety signals and providing better product information for medicines authorised in Europe. The system is obligatory for clinical trial sponsors and marketing authorisation holders in Europe.
Following marketing approval and granting of a product licence for a new drug, observational Phase IV studies will often be performed either by the pharmaceutical company or professional organisations. This could involve implementation and analysis of databases or registries surrounding use of the medication in a real‐world setting. For example, the UK GP database was used to confirm a link between the oral contraceptive and the risk of deep vein thrombosis, while pharmaceutical companies that manufacture direct oral anticoagulants have conducted observational Phase IV studies to assess if the benefits that were observed compared to warfarin in Phase III trials remain evident when studied in real‐world populations.
If observational studies or meta‐analysis of randomised control trials raise concern about a particular medication, the options are for the company to withdraw the drug or the regulatory authorities to suspend the licence until the concern is investigated further. In the UK, a drug is marked with a black triangle in the BNF if it is thought to cause concern and prescribers are encouraged to report any problems through the yellow card scheme.
Yellow card scheme
In the UK, the Yellow Card scheme helps the MHRA to monitor the safety of drugs and other healthcare products. Prescribers are asked to report drug side effects or adverse drug reactions by completing a ‘Yellow Card’ which can be done online. In the BNF, all new drugs have a label reminding prescribers to report any side effects using this process. The MHRA monitors these reports carefully. If a new side effect is identified, information is carefully considered in the context of the overall side‐effect profile for the medicine, and how the side‐effect profile compares with other medicines used to treat the same condition. The MHRA is advised by the CHM, which is the Government's independent scientific advisory body on medicines safety that is made up of experts from a range of health professionals and includes lay representatives. Where necessary, action is taken based on the balance of benefit and risk to ensure that medicines are used in a way that minimises risk while maximising benefit for patients.
3 Pharmacoeconomics: the economic evaluation of new drugs
A 45‐year‐old man has recently been diagnosed with advanced cancer. He attends clinic to discuss treatment options and has brought with him several printouts from the Internet which he wants to ask you about. He has read that there is a new drug for his condition which has shown some promising early results in a Phase III clinical trial. The drug showed some modest survival benefits compared with current standard therapy, alongside relatively manageable side effects, and your patient would therefore like to be prescribed the drug. However, you know that this new medicine is very expensive and that it has recently had a health economic evaluation. The result is that it is not recommended for use for patients you look after. What tools are used by health economists to decide whether a drug offers value for money?
Introduction – why do we need economic evaluations?
In the last few decades, there has been an increased interest in applying economic analysis to healthcare interventions, as evidenced by the use of such evaluations by organisations such as the National Institute for Health and Care Excellence (NICE) and the Scottish Medicines Consortium (SMC) in the UK. The reason relates to a basic problem in economics: tackling the linked issues of scarcity and choice.
Resource scarcity in healthcare systems means that choices have to be made on how resources are spent
Economic evaluations are increasingly used in healthcare decision‐making to provide an indicator of the cost‐effectiveness of different treatment options and aid resource allocation decisions
Cost–utility analysis is a commonly used type of economic evaluation used by health technology assessment agencies
Quality‐adjusted life years (QALYs) are a standard outcome measure used to capture both the morbidity and mortality profile associated with a disease and its treatment
Scarcity of resources exists in healthcare systems worldwide, and means that there will never be sufficient funds to meet all the competing demands for healthcare. Difficult choices have to be made over how to spend resources in order to meet the many objectives of the healthcare system.
Pharmacoeconomics, defined as the economic evaluation of pharmaceutical interventions, is often used by healthcare decision makers in the NHS and elsewhere. It is increasingly also used by pharmaceutical companies, who have to demonstrate the cost‐effectiveness of new drugs in addition to achieving the traditional hurdles of safety and efficacy required for drug licencing.
Economic evaluation
Economic evaluation is defined as the comparative analysis of alternative courses of action in terms of both their costs and consequences (Drummond et al. 2015). Such evaluation can provide a systematic way of considering solutions to the problems of scarcity and choice that are faced in the healthcare system. The aim is to identify what is most efficient, defined as the greatest amount of health benefit that can be bought for a given level of resource.
Perspective
The specific costs and benefits that are included in any economic evaluation depend on the perspective that has been chosen for the analysis. The perspective is often that of the ‘healthcare payer’, who is generally only interested in the direct costs to the healthcare system and benefits to the patient treated. Alternatively, a ‘societal’ perspective may be adopted, which will aim to take into account a much wider range of costs and benefits by, for example, including costs that are borne by patients themselves, the income losses patients experience as a consequence of being ill or the wider benefits by reducing demands on social security resources. While the societal perspective may seem more logical and comprehensive, many of the costs and benefits are hard to quantify and/or realise.
Costs
Cost, in a health economic evaluation, comes in many forms and is more than the simple acquisition cost of the drug in question.
One of the key concepts in economic evaluation is that of opportunity cost. This is defined as the benefit foregone when selecting one course of action rather than another. When resources are limited, the decision to spend money in one way means that we cannot spend the money on something else, and therefore are foregoing the benefits associated with the thing we can no longer do. In a competitive market, opportunity costs should be reflected by market prices, but where they are not (as is usually the case in healthcare systems), opportunity costs have to be estimated by economists.
Economists also distinguish between direct, indirect and intangible costs. Direct costs are those that are consumed in the provision of a health intervention, e.g. staff costs, hospital operating costs, drug acquisition