Name of Lead Author: Professor David Webb
Organization: British Pharmacological Society
Country: United Kingdom

Abstract

The British Pharmacological Society (BPS) is a UK learned society with the mission of promoting and advancing the whole spectrum of pharmacology, and a leading organisation in the practical application of pharmacology around the world. BPS acknowledges the importance of the various criteria outlined in the Call for Contributions around widening access to medicines and seeks to contribute in the areas of ‘Impact on Public Health’ and ‘Implementation’.

The importance of adequate healthcare infrastructure and systems, to allow newer medicines to be used appropriately, monitored as necessary and for adverse effects to be managed effectively is emphasised. The specialist skills of pharmacologists are felt to be particularly useful for the task of managing medicines utilisation.

The processes and activities required to maximise the benefits, in terms of population health, of widened access to medicines, and the roles in which pharmacologists could/should take leadership roles to optimise the use of medicines, maximising benefits and minimising (or managing) risks, are described. These processes/activities are categorised by the locus of intervention, namely national or regional/local levels.

Wider access to medicines will only achieve the greatest impact on population health if the outlined processes/activities form a central part of implementation procedures, and are carefully integrated such that prescribers get clear and consistent advice and information. The training and experience of pharmacologists in all of these areas place them, almost uniquely, in the ideal situation to ensure the essential harmonisation and consistency of advice.

Although there are individual physicians with informal interests in therapeutics and clinical pharmacology in most countries, those with the best training and experience to provide leadership in the context of wider access to medicines (namely clinically-trained pharmacologists) are in particularly short supply in developing countries, where widened access to medicines will pose real medicines management challenges.

Submission

The British Pharmacological Society (BPS) is the primary UK learned society concerned with research into drugs and the way they work. Our nearly 4,000 members work in academia, industry, regulatory agencies and the health services, and many are medically qualified. The Society covers the whole spectrum of pharmacology, including laboratory, clinical, and toxicological aspects.

BPS is pleased to have the opportunity to offer its input to the deliberations of the UN Secretary-General’s High-Level Panel on Access to Medicines. We note the main focus of the Panel on policy incoherence, particularly lack of coherence amongst the needs of medicines developers, the precepts of human rights legislation and the requirements of trade legislation. These are very important issues that we readily acknowledge impact on access to medicines worldwide, but they are not primary areas of expertise for the BPS.

We also note, however, that the panel seeks contributions in the areas of ‘Impact on Public Health’ and ‘Implementation’, and it is in these areas that we believe we have experience and expertise which may be of value.

While access to medicines is a public health issue in all countries, we believe that simply improving access, both to old and new medicines, will not, of itself, improve public health outcomes optimally. Healthcare infrastructure must be in place to allow newer medicines to be used appropriately, monitored as necessary and for adverse effects to be managed effectively. Thus, for example, wider access to medicines for reducing cardiovascular risk will still require the availability of methods to measure underlying cardiovascular risk (blood pressure and lipids levels), while newer medicines for treatment of diabetes requite access to blood glucose measuring technologies. Some drugs require monitoring of plasma levels of the drug in order that they are used effectively and safely (e.g. gentamicin, some anticonvulsants). New biologic agents such as anti-TNF medicines are highly effective in many inflammatory diseases but can produce serious adverse effects (e.g. re-activation of tuberculosis, invasive fungal infections) – the balance of risk and benefit with these medicines only favours benefit if methods to identify and monitor these serious adverse effects are in place.

Beyond ensuring that the appropriate healthcare infrastructure is in place, improved access to medicines will produce the best population health outcomes only if they are used most appropriately, which requires that they are managed within the prevailing healthcare system. The task of managing medicines utilisation is one where the skills of pharmacologists, including those with additional clinical training (referred to as ‘clinical pharmacologists’), are particularly useful (Aronson, 2010; Birkett et al., 2010).

The last decade in particular has seen the role of clinical pharmacologists in high-income countries develop significantly, moving them from a largely research role into leaders in areas of medicines policy development, prescribing monitoring and management of medicines use. Such developments have not always been mirrored in other countries, where many (even the majority) of clinically trained pharmacologists working in medicines research and development, often in the pharmaceutical industry, leaving the healthcare system without their important expertise (Zagorodnikova et al., 2015)

We hope it will be useful to outline in more detail the processes we feel are required to maximise the benefits of wider access to medicines and the roles in which pharmacologists can and do take leadership roles to maximise the benefits (and minimise the risks) of drug therapy (Aronson, 2012a and 2012b)

Processes and Activities at National Level

Drug licensing/registration – with widened access to medicines, it will be important that national drug licensing/registration processes are in place in each country to ensure that the ‘risk:benefit’ profile of each medicine favours benefit over risk in the population of each country. Racial, genetic and co-morbidity factors may make the risk:benefit assessment different in different populations, or at least identify sub-groups of patients in whom the risk:benefit profile may be adverse. Pharmacologists are ideally trained to lead on these assessments and ensure that new medicines are really likely to benefit overall health.

Health Technology Assessment – health technology assessment (HTA) is defined as “the systematic evaluation of the properties and effects of a health technology, addressing the direct and intended effects of this technology, as well as its indirect and unintended consequences, and aimed mainly at informing decision-making regarding health technologies”. It is highly appropriate that medicines are subject to HTA if the most efficient use of limited financial resource is to be achieved. Those countries which have adopted a robust HTA approach to medicines (e.g. United Kingdom, Sweden, Australia, Canada) have shown repeatedly that newer and more expensive medicines do not necessarily lead to improved patient outcomes, and that for many patients very similar outcomes can be achieved with the use of older (and usually considerably cheaper) drugs. This frees resources in the healthcare system for the use of more expensive products of proven clinical advantage where appropriate, achieving greater population health-gain with the same use of resources.

Clinical pharmacologists are very well placed to lead on HTA of medicines, providing useful clinical and scientific inputs to sit alongside inputs from (for example) health economists. Experience in the UK suggests that it is the clinical uncertainties (rather than economic uncertainties) that pose the biggest challenges in HTA of medicines and so those with pharmacological expertise are of particular value.

It is noteworthy that the founding Chairs of the 3 national medicines HTA bodies in the UK (the National Institute for Health and Care Excellence (NICE), the Scottish Medicines Consortium (SMC) and the All-Wales Medicines Strategy Group (AWMSG)) were all clinical pharmacologists, as have been many of their successors.

Guideline development – rational and efficient use of medicines can be helped by the development of locally-relevant evidence-based clinical guidelines. These aim to ensure that the right medicine(s) get to each patient to maximise the health benefits while avoiding over-treatment, which wastes resource and may lead to undesirable side-effects for patients. Clinical pharmacologists are well placed to be involved, alongside relevant clinical specialists, in developing such guidelines; though there are many internationally-developed guidelines available, evidence suggests that developing guidelines locally (or adapting international guidelines to local circumstances) improves adherence to the guideline, optimising its impact.

While clinical specialists have a key role in guideline development, the clinical pharmacologist adds value from a more detailed knowledge of the individual medicines and also an understanding of potential problems (such as drug:drug interactions) in patients with multiple co-morbidities, an increasingly common situation in all countries.

Formulary development – the development of a formulary or ‘limited list’ of medicines that are therapies of first or second choice can improve both the effectiveness and safety of prescribing. Prescribers become familiar with a small number of frequently used medicines, aware of indications, dosage and adverse effects; this can avoid prescribing errors, which otherwise can have adverse outcomes. Use of the same ‘formulary’ in primary and secondary care facilitates patient care as they move between these sectors and avoids undesirable changes in therapy.

Hospital and community pharmacies can also hold stocks of fewer individual medicines; that simplifies and reduces their workload and may allow financial savings if less total drug stock has to be held. Adherence to formulary recommendations can also be a useful index of prescribing quality and can be fed back to individual prescribers with a view to quality improvement.

The formulary content should be carefully harmonised with the content of clinical guidelines and outcome of medicines HTA reviews to avoid any ‘mixed messages’ to prescribers. Clinical pharmacologists are ideally placed to develop and maintain formularies. Note that in larger countries, or where there is significant heterogeneity in healthcare provision within a country, it may be appropriate to develop formularies at more local or regional levels (see other activities below) (Reynolds, Fajemisin and Wilds, 2012).

Processes and Activities at Regional/Local Level

Education of prescribers – wider availability of medicines will require substantial educational input to prescribers to ensure that medicines are used effectively and safely. While some of this work can be done through guidelines (see above), there is also a need for more personalised education delivered directly to prescribers. This is particularly true in the context of multiple co-morbidities, which may find prescribers faced with significant poly-pharmacy (many medicines) and, for some patients, conflicting or mutually exclusive treatment options. In these circumstances, real knowledge and understanding of medicines, rather than simple following of guidelines or protocols, are essential. Indeed, there may be circumstances in which knowledge of medicines and good prescribing practice may require to be formally assessed before allowing an individual clinician to prescribe.

Individual prescribers or clinical specialists may take a lead in these initiatives, but there is a significant risk that educational and assessment activities will be overlooked in the general enthusiasm to introduce new therapeutic options. Clinical pharmacologists are ideally placed to act as leaders, developing and delivering education and assessment packages and co-ordinating the activities and inputs of others (Williams, 2012).

Good prescribing practice and medication errors – widened access to medicines will only be safe and effective if the right medicine (at the right dose, the right time and the right route of administration) gets to each patient. Prescription errors are a significant patient safety concern in all healthcare systems. While education can help reduce errors, it is important that good prescribing processes (and recording of prescribing) are in place as getting these processes correct can significantly reduce the risk of errors. In addition, monitoring of actual errors, analysis of causes, feedback to prescribers and improvements to prescribing practice are all needed to create a safety culture and minimize the risks to patients. Clinical pharmacologists are trained in this area and can take a system-wide approach to minimizing errors and improving safety in all clinical areas (e.g. primary and secondary care) (Agrawal et al., 2009).

Local protocol development – while nationally-developed evidence-based guidelines are very important, there will frequently also be the need to develop local prescribing protocols, showing how guideline recommendations are to be implemented in clinical settings at local or regional level. Clinical specialists need to be closely involved, but again clinical pharmacologists can take a lead role in protocol development. Indeed, by overseeing protocol developments across a wide range of therapies, they can ensure consistency of approach and harmonisation across protocols, both important to promote the safest use of old and new medicines (Reynolds and Barker, 2012).

Anti-microbial stewardship – the worldwide developing problem of anti-microbial resistance is a challenge to all healthcare systems and to public health policy. Programmes aimed at controlling the use of anti-microbials, both in terms of number of patients treated and type of anti-microbial used, can make significant positive differences to patterns of antimicrobial resistance. Such programmes often involve use of locally-developed protocols or guidelines, coupled with monitoring of actual anti-microbial prescribing (and anti-microbial resistance patterns) and feedback to prescribers on adherence to protocols (or even incentivising prescribers to follow guidelines). These programmes are often described as ‘anti-microbial stewardship’.

Clinical pharmacologists are trained in good anti-microbial use, can readily act as a link between microbiologists and prescribers (around local patterns of anti-microbial resistance), and understand (and can develop) methods of monitoring prescribing to allow the feedback which has been shown to be a big driver of prescribing change.

Additional Notes on Processes and Activities

Wider access to medicines will, we believe, only achieve the greatest positive impact on population health if these processes and activities form a central part of the implementation procedure. In the ideal scenario, these processes and activities would be in place, tried and tested before additional therapy options were introduced, but if this is not possible then the new processes should be introduced alongside new medicines as part of wider access implementation.

Most importantly, the processes and activities described above must all be carefully integrated such that prescribers get clear and consistent advice and information. For example, only licensed medicines should be subject to HTA, and only medicines approved by HTA should be recommended in clinical guidelines, local protocols and be found in formularies, while educational activities should focus on medicines in formularies and protocols. This aim should maximise the appropriate use of medicines and minimise inappropriate use (or use of inappropriate medicines), bringing the greatest patient (and public health) benefits at the least cost, thus allowing even more patients to be treated.

While individual clinical specialists, both physicians and pharmacists, have much to contribute to many of these processes and activities, the training and experience of clinical pharmacologists in ALL of these areas places them, almost uniquely, in the ideal situation to ensure the essential harmonisation and consistency of advice.

Clinical Pharmacology in Developing Countries

We have noted that clinical pharmacologists are well placed to take leading roles in the implementation activities described above. The specialty is small but well developed in higher-income developed countries but the situation is rather different elsewhere. The status of clinical pharmacology in developing countries was reviewed in 2013 by Walubo (2013) – it would not be sensible to attempt to summarise his excellent paper here, but some interesting points include:

• Of 52 African countries, only 5 have a pharmacology society and only 1 (South Africa) recognises the specialty of clinical pharmacology
• Of 18 Latin American countries, only 7 have a pharmacology society and none recognises the specialty of clinical pharmacology
• Of 26 Asian countries, only 8 have a pharmacology society and only 3 (Philippines, India and Thailand) recognise the specialty of clinical pharmacology

While there are probably individual physicians with informal interests in therapeutics and clinical pharmacology in most countries, we believe that the above data suggest that those with the best training and experience to provide leadership in the context of wider access to medicines are in short supply. Even in India, where training programmes and specialty recognition exist, the great majority of clinical pharmacologists work within the pharmaceutical industry, possibly making their skills unavailable to the health-care system (Kshirsagar et al., 2013).

While, as noted above, we regard the implementation processes and activities as more important than the identity of those providing leadership, we think that development of ‘medicines management leaders’ in countries with limited clinical pharmacology resources is a priority alongside wider access to medicines (Lehmann, Stork and Guharoy, 2006).

Summary of main points:

• Adequate healthcare infrastructure and systems must be in place to allow both newer and current medicines to be used appropriately, monitored as necessary and for adverse effects to be managed effectively.
• Clinically trained pharmacologists have many skills to offer in the task of managing medicines within the healthcare system.
• Processes and activities should be built or improved at national level in anticipation of widened access to medicines by establishing drug licensing/registration systems, conducting the systematic evaluation of the properties and effects of health technologies, and developing locally-relevant evidence-based clinical guidelines and formularies or “limited lists” of medicines that are therapies of first or second choice.
• Processes and activities should be built or improved at regional/local level by providing education for prescribers, developing local prescribing protocols and mechanisms for anti-microbial stewardship.
• These processes and activities should form a central part of the implementation procedure of widening access to medicines and should be carefully integrated.

Bibliography and References

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