Quality use of medicines in the community: the Australian experience

Introduction

It is surprising that countries which for many years have had a strong regulatory system for medicinal drugs, and have provided financial support from the public purse to ensure that the disadvantaged in society have access to them, have only recently begun to be concerned about the quality of use, and cost-effectiveness, of those medicines in the community.

In Australia, one of the stimuli for concern has been the rapidly increasing cost of medicines to whomever pays – be it the individual, the Federal or State Government, or some other third-party payer. Another, undoubtedly, has been the increasing pressure to align the use of medicines with best evidence derived from the increasing number of high quality, randomised, controlled trials. An important third factor has been political pressure from vocal and informed consumer groups who have put their case to government and have drawn health professionals and the pharmaceutical industry into a debate on the need for a set of national medicinal drug policies.

Over the past decade, these pressures have created novel and sometimes contentious responses. Almost all Australian clinical pharmacologists have found themselves involved in helping to shape, or implement, medicinal drug policy, and have been obliged to push back the boundaries of what has been, at times, a too narrowly defined specialty. In doing this, they have had to build unanticipated partnerships (for example, with epidemiologists and economists), and to learn to implement new approaches as members of a team that often comprises other health professionals, consumers, the pharmaceutical industry, and government.

Far from perceiving this as a threat, most clinical pharmacologists have enjoyed their expanded role – often with the feeling that their expertise is only now being harnessed appropriately to ensure that the community gets the best out of its medicines.

Pharmacoeconomics and the cost-effectiveness of medicines

Clinical trials undertaken for marketing approval of drugs generally provide little insight regarding either the relative effectiveness of drugs or their cost-effectiveness. For physicians who must choose between treatments, and governments that must subsidize the costs, these are important issues.

In Australia, as elsewhere, quality, safety and efficacy are the three factors that determine whether a drug is approved for marketing. In the selection of drugs for public subsidy, however, the criterion of cost-effectiveness, imposed in 1993 by legislative amendment, also applies [1]. As a result, economic evaluation has become a core component of the National Medicines Policy. It comprises a set of formal, quantitative methods to compare alternative strategies in terms of their resource use and their expected outcomes [2]. The process is intended to inform resource allocation decisions, not make them.

Although the concept of this form of economic analysis is not new, and the literature on the techniques involved is over 30 years old [3], the role of this ‘fourth hurdle’[4] in the pricing and reimbursement of medicines has been debated widely, both in Australia and beyond.

The Pharmaceutical Benefits Scheme (PBS) is a comprehensive, publicly funded insurance program, in operation for almost 50 years, that reimburses pharmacists for the costs of drugs listed on the Schedule of Pharmaceutical Benefits. Some 1600 different products (representing approximately 540 drugs) are listed from a total of around 10 730 registered for marketing [5]. In 1997/8, approximately 125 m prescriptions were dispensed at a cost of A$2.8 billion, roughly 10% of government healthcare expenditure [6]. As all 18 million Australians are eligible to obtain subsidy for prescribed drugs listed on the Schedule, the PBS represents a considerable market. Levels of copayment are determined by age, illness, and income.

The requirements (for pharmaceutical manufacturers) to support a listing application and requested price for a new drug, or the alteration of an existing listing, are set out in published guidelines [7]. The sponsor company is required to relate the clinical outcomes of treatment with the new drug to the costs associated with its use. These must be compared with the costs and outcomes of the treatment that it is most likely to replace. The guidelines express a preference, on the grounds of scientific rigour, for economic evaluations using evidence from randomised, as opposed to nonrandomised, trials. There is also a preference for randomised trials that directly compare the proposed drug with its main comparator. Where no such ‘head to head’ trials are available, the use of ‘common comparator’ trials, where both the new drug and the comparator are tested against a common reference therapy (usually placebo) is encouraged.

The selection of drugs for listing on the Schedule is a two step process. The first is the preparation of a detailed commentary on the economic evaluation submitted by the industry sponsor. This is performed by a team of clinicians, clinical pharmacologists, pharmacists, biostatisticians, epidemiologists, and health economists. The second is review of the sponsor's submission and of the commentary by an expert economics subcommittee (ESC) comprising clinicians, health economists, epidemiologists, and biostatisticians, to determine whether the data presented support the claims of efficacy and cost-effectiveness being made by the sponsor. The ESC then provides advice to the Pharmaceutical Benefits Advisory Committee (PBAC) which has the legislated power to recommend drugs for subsidy. The sponsor company is provided with a copy of the detailed commentary and may provide responses to issues raised by the evaluators for consideration by the PBAC.

The multidisciplinary approach at both stages reflects the clinical, economic and statistical interfaces involved. Trial based clinical evidence is the starting point for claims made in respect of drugs proposed for listing but, given finite resources, that evidence must be viewed from statistical and economic perspectives as well, if decisions are to support equitable use of those resources.

Although the approach is primarily evidence-based, opinion is not excluded, as it is also necessary to interpret the data. In practice, the clinical comparison, which requires both assessment of the trial evidence and consideration of the clinical relevance to PBS patients of the trial outcomes, has been found to dominate the economic comparison. Thus the role of clinical pharmacologists in the process becomes a key one.

The primary purpose of economic evaluation is to ensure the cost-effectiveness of drugs recommended for subsidy. The process is not intended to act as a cost containment instrument, although in some cases it may have this effect. For example, a new, clinically equivalent addition to an existing class of drugs will be listed at the same price as the others in the group, provided the data support the claim of equivalence. Cost-effectiveness data may identify selected patients for whom the drug confers the greatest incremental benefit and listing may be recommended only for these groups. Notwithstanding the evidence-based foundations, the listing process is not without an element of altruism, as, in making listing recommendations, the PBAC adopts a societal perspective and takes into account issues such as equity, access, and the need for a drug. As a result, agents have been listed despite extremely high incremental cost-effectiveness ratios.

When listing applications are rejected, the reasons are explained and the sponsor company may choose to undertake a resubmission addressing the areas of contention. This may have the effect of targeting use to specific populations for whom there is evidence that use is cost-effective. After listing, use is monitored, and if there is evidence of ‘leakage’ beyond the approved indication, then pricing may be renegotiated.

Economic evaluation seeks to support quality use of medicines in that it represents an attempt to assess objectively the benefits associated with using a particular drug. Of itself, it cannot ensure quality use of medicines, although its mandatory use in Australia is a vote of faith in the merits of evidence-based decision making. Incorporating clinical, pharmacological, economic, and statistical expertise, it recognizes that the repertoire of what may be prescribed can be improved by inputs other than the purely clinical.

Quality use of medicines (QUM)

A system that guarantees quality, safety and efficacy of medicines, makes them accessible in an equitable way and favours use of compounds that can be shown to be cost-effective, goes a long way towards building a framework for rational drug use. It cannot of course guarantee this, as the ways in which drugs are prescribed, purchased and administered are the ultimate determinants of drug-related benefit and harm in the community.

In 1991, the Australian Consumers' Health Forum joined forces with the Australasian Society for Clinical and Experimental Pharmacologists (ASCEP – later to become ASCEPT with the inclusion of toxicologists) to run a workshop –‘Rational Prescribing: a challenge for medical educators’[8]. The narrow boundaries of the title were soon outstripped by the content, and discussion focused on national medicinal drug policies, and, amongst other things, Australia's conspicuous lack of such a document. Shortly after, with the support of the, then, federal Minister of Health, a policy on Quality Use of Medicines (QUM) was adopted [9], and this provided the needed political impetus, even though it only dealt with one of the four ‘arms’ of our present National Medicines Policy. Australia's National Medicines Policy 2000 aims to achieve:

• Timely access to the medicines that Australians need, at a cost individuals and the community can afford.

• Availability of medicines meeting appropriate standards of quality, safety, and efficacy.

• Quality use of medicines.

• Maintenance of a responsible and viable medicines industry.

The complete and revised National Medicines Policy was formally launched on December 10, 1999, and can be seen at, and downloaded from, http://www.health.gov.au/haf/docs/nmp2000.htm

The Commonwealth Government established two committees to advise the Minister of Health on QUM. The first is APAC – the Australian Pharmaceutical Advisory Council, a body representing all the stakeholders in QUM, which has concerned itself with policy and achieving national consensus on specific issues, for example, the incorporation of a formal system of medication review as an accreditation criterion for nursing homes, or the establishment of a national system for disposing of unwanted medicines.

The second, the Pharmaceutical Health and Rational Use of Medicines (which generates the euphonious acronym, -PHARM-) Committee, is a group chosen for individual expertise in the field of rational drug use. All relevant stakeholders are represented, and the committee has embraced the partnership principle in order to explore issues to do with Quality Use of Medicines in any relevant field. An annual budget permits a modest research grant program, and projects are selected for funding in line with the well publicised strategic areas of the committee. The approach favoured is that of the problem-solving algorithm – defining and clarifying problems, exploring causes, and testing in a scientifically rigorous way putative interventions. If effective interventions are identified, they may be passed to APAC for national implementation.

The Commonwealth Government has funded over 150 projects recommended to it by PHARM and, as momentum gathered, other bodies began to recognize the importance of improving the quality use of medicines For example, professional Colleges and State Governments helped to fund QUM project work. PHARM has recently collated as many of these projects as can be identified (over 700 of them), and set them into a QUM map [http://www.health.gov.au–-select the link to Quality Use of Medicines Mapping Project], which makes it possible to see where projects have taken place, the nature of the methodology, extent of funding, and in general terms, the outcome and evaluation. This QUM map becomes a strategic tool for evaluation, and for building on and generalizing successful initiatives.

In recent years, Government, on PHARM's advice, has established three postgraduate scholarships annually for graduates wanting to work in the general area of QUM. There are eight QUM scholars in post at present, the first scholar having received her PhD in 1999. Through this scheme, it is hoped to encourage graduates into QUM as a legitimate field for scientific study, and to assist in the training of future leaders in the area.

Despite evidence that QUM was establishing itself on the national agenda, exploratory work in the mid-1990s showed that prescribing in Australia was less than optimal and constituted a major problem in the quest for better use of medicines. For example, there were unacceptably high rates of prescribing of antibiotics and benzodiazepines, and under-prescribing of inhaled corticosteroids in chronic asthma.

The annual resources available to PHARM were too small to tackle these issues, which clearly needed a new initiative. This came in the 1997 Budget when the Minister of Health announced funding for a new National Prescribing Service for Australia aimed at improving the standards of prescribing, of prescribing education (at all levels, from students to doctors in career positions) and of the supports necessary for optimal prescribing at the point of decision.

The National Prescribing Service (NPS)

By 1997, a great deal had been learnt about the way in which medicines were being used in Australia. A national survey performed regularly by the Drug Utilization Sub-Committee of the Pharmaceutical Benefits Advisory Committee provides a measure of overall prescribing [10]. But without any ability to link prescribing to indication, it is usually only possible, from the aggregate data, to infer appropriateness.

Specialized surveys of drug utilization, in which appropriateness can be assessed, are often carried out in hospitals, but such data are rare from community sources. Thus, although it was felt that many of the prescribing issues could be inferred, and many of the needed behavioural change techniques were well established in the literature, the Advisory Board charged with setting up the NPS felt it best to consult widely throughout the country before strategies to improve prescribing were put in place. Written submissions were obtained after invitations in the national press, and these were supplemented by face-to-face meetings in the capital cities of each State. The collated views were referred back to over 60 of the more than 100 divisions of general practice, and at each meeting other health professionals and consumers were present. Finally, after 8 months of enquiry, it was possible to put together a strategic plan for the NPS [11]. At least as important, many health practitioners and consumers had had the opportunity to engage in the debate and to make their personal suggestions for the national agenda. The degree of consensus among all who contributed was remarkable.

The NPS was incorporated as a not-for-profit company, and with a clear mandate. The major strategies to be implemented all came from the consultation process.

First and foremost were activities collectively setting in place the ‘quality assurance cycle’, in prescribing-particularly in general practice. The NPS provides regular feedback of prescribing data to individual practitioners. The data are set alongside age-and practice-type-adjusted averages for other practitioners. Earlier research [12] had confirmed the view that written feedback of prescribing data alone was unlikely to modify prescribing practice. Individual data therefore are always accompanied by evidence-based information related to the group of drugs under scrutiny. As this process unfolds, divisions of general practice (usually around 100 practitioners in each) are gradually taking up the offer to enlist the services of NPS facilitators who work with the divisions to enhance the quality of prescribing. By the end of 2000, it is anticipated that around half of all general practitioners will be reached by this service which utilizes the techniques of ‘academic detailing’[13], to focus on specific and important prescribing issues.

A second strategy is to enhance the availability and use of objective sources of medicines information – a common request from doctors during the consultation. The Australian Medicines Handbook [http://www.amh.net.au], the publications of Therapeutic Guidelines Ltd [http://www.tg.com.au], and the Australian Prescriber [http://www.australianprescriber.com] represent three sources of objective information, but making this information available at the point of prescribing decision is the major challenge. All of these resources will be available electronically by mid-2000, and the vision is that of a single, consolidated, decision support system available to doctors at their desktop PCs. The logistics of linking the three sources, coupled with the present low (but rising rapidly) use of computers for clinical decision support in Australia, present the main obstacles.

The third area of concern is prescribing education, and this has become a major issue for clinical pharmacologists. The quality of medical student education in pharmacology and clinical pharmacology in Australian medical schools is, on the whole, good, but none of the 10 schools provides a systematic, ‘hands on’ course to teach the cognitive and behavioural skills of prescribing. For the past year, clinical pharmacologists from all of the medical schools have been working together under the aegis of the NPS to devise a modular prescribing curriculum for final year medical students, emphasizing the skills they will put into practice as they move into intern/house officer jobs in hospitals. The program embodies many of the principles of the WHO ‘Guide to Good Prescribing’ approach [14].

The modules will be produced in web-interactive format, as many senior medical students spend much of their time away from the principal teaching hospitals – often in remote and rural placements – but have access to web-based material.

Pilot testing of the curriculum and training of facilitators will take place in the year 2000 in the hope of implementation nationally in 2001.

The vision for education in prescribing extends from the senior medical student period in continuity into the intern year, into prevocational, and then on into College-based vocational training and continuing medical education.

The need to evaluate the activities of the NPS has been acknowledged, and a strong evaluation group has been put together to devise and implement indicators of progress.

The view from Government and Industry

Government (and particularly the Department of Finance) tends to see pharmaceuticals as an uncapped drain of finance from the Health Budget. Certainly, Government looks to some containment of burgeoning expenditure from, particularly, the economic evaluation of medicines as a prerequisite to listing on the Pharmaceutical Benefits Scheme, and from several of the strategies embraced by the National Prescribing Service.

Others, in and out of Government, with a wider vision, see these activities as a means of bringing evidence to bear on drug utilization, and of improving health outcomes by optimizing drug use. For them, the separation of health outcomes from the purely financial considerations of drug costs is irrational, and at root, an artefact of Government compartmentalism. Indeed more expenditure on drugs in some areas (untreated hypertension, chronic asthma) would probably bring disproportionate benefits.

Although Australia, with its small population and distance from the leading pharmaceutical markets of Europe and America, has never been a major drug manufacturer, its institutions have been active in fundamental drug discovery (with further development commonly undertaken elsewhere). In legislating that new medicines fulfil the criterion of cost-effectiveness before being listed for public subsidy, it has acknowledged, in practical terms, the ideal that health care resources should be used to their maximum advantage. The pharmaceutical industry, meanwhile is naturally somewhat ambivalent. While it is difficult to argue convincingly against quality use of medicines, the cost-effectiveness step in PBS listing has the potential to drive down some drug prices. Australia represents a very small fraction of the global pharmaceutical market, but bench marking of drugs based on Australian prices could contain profits – particularly from other drugs of an existing class which are now commonly pegged to the same price as the innovator brand. On the other hand, the situation where manufacturers of generic products undercut prices of branded agents is avoided.

Industry has a seat on APAC, PHARM, and on the Board of the National Prescribing Service, and many individuals from industry in Australia have contributed substantially in thought, time and effort, to QUM. However, the inherent contradiction between best quality of use of medicines and the commercial imperative to maximize profits, has the risk of putting these individuals in an impossible position. The partnership between industry and QUM is never likely to be consistently comfortable!

Finally, after the flurry of activity engendered 10 years ago by the consumer organizations, we are reaching the point where, going full circle, consumer education is high on the agenda of all the national committees. An informed and energetic consumer sector has the capacity to influence government, keep committees honest, and help adjudicate where evidence and information about drug use spill over into aggressive promotion which may run counter to the public interest.

Many years ago, in the pages of this journal [15], the role of the clinical pharmacologist in the ‘district general hospital’ was a hotly debated topic. Many of us working in Australia today would claim that, as a specialty, our focus has for many years been far too narrow, and that it is only as we work collaboratively with others to improve quality use of medicines in the community that clinical pharmacologists are able to realize their full potential without sacrificing the basic scientific ingredients that forged the specialty in the first place.