False assumptions about the cost of combination drug therapies for HIV are skewing funding decisions. Mike Youle and colleagues argue that a new approach to analysing cost effectiveness is needed

Increasing pressure on the pharmaceutical component of healthcare budgets has prompted governments, including the UK's, to establish economic criteria for the licensing, reimbursement or formulary acceptance of new medicines.

The most common hurdle to overcome in the introduction of new therapeutic interventions with proven clinical effectiveness is the perceived expense of the drug therapy.

The pharmaceutical industry has acknowledged the importance of cost-effectiveness data in arguing the case for particular agents to be used. Both industry and the health service recognise the need for reliable data, such as that provided by purpose-designed information systems and databases, to support economic studies.

The ultimate aim of both parties is to show the cost effectiveness of interventions - but for differing reasons.

The NHS needs to show that it is making best use of limited resources and to justify the provision of seemingly expensive therapies. Conversely, the industry needs to present the cost-effectiveness of therapies as a marketing tool in an evidence-based healthcare environment.

But even with the demonstration of clear economic benefits for certain interventions, such as the use of smoking cessation products, the health service has been slow to adopt changes in prescribing based on pharmacoeconomic evidence.

1There are various reasons for this: structural inertia in the service, fears of initial cost-burden and rampant shorttermism in budgetary planning.

Another reason is the segregation of budgets:

commonly, pay and non-pay are separated, as are capital and other expenditure, so that using an expensive drug which saves staff time may involve transferring money from one budget line or budget holder to another.

Nor are savings always recoverable. For example, reductions in length of stay cannot always be accredited to a directorate, particularly when beds are continually in short supply and there are staff shortages.

Similarly, a saving in one cost may be offset by increased patient throughput, although this should help reduce waiting lists for elective beds.

There is also poor interaction between health economists and health service managers. The latter are commonly semi-business orientated and focus on costs at the expense of outcomes - particularly when faced with orders to make continual 'efficiency savings' each year, with no opportunity to demonstrate the benefits of a longterm strategy.

If there are to be evidence-based national service frameworks, the importance of health economics within a particular disease state and the need to be able to measure cost-effectiveness becomes central to the evidence base used in clinical decision-making. The National Institute for Clinical Excellence might go some way to fulfilling this need.

New therapies for HIV

The advent of effective antiretroviral therapy to treat the rising numbers of HIV-infected individuals has precipitated a financial crisis within health authorities of unprecedented dimensions.

In a specialty such as HIV, in which rapid treatment advances are continually being made, cost-effectiveness data is largely generated on the basis of population modelling. Unfortunately, some HAs have been unwilling to fund appropriate combination therapies in the absence of prospective long-term studies, leading to regional inequalities in access to antiretrovirals and 'treatment by postcode' (see cover feature, 17 June).

There is a misguided assumption that the shift from mono-therapy to combination therapies results in a proportional increase in drug expenditure, regardless of any subsequent health gains. This has resulted in some HAs rationing therapy, causing many patients not to receive the accepted standard of care.

2As the types of drug combinations used change, based on scientific advances and the need to thwart the ability of HIV to mutate rapidly, it is vital to explode the myth that using more agents costs more money. In addition, those holding the purse strings must appreciate that the accountancy cost of a drug combination is often unrelated to the cost-effectiveness of the intervention.

Data is collected, as requested by purchasers and government bodies, at trust level on the number of antiretroviral drugs prescribed per patient. But this does not accurately reflect drug expenditure.

Some of the larger HAs purchasing HIV-related care have used models to assist them in translating this unitary drug data into cost data, with varying success. It may have been relevant when the drug dosage in a regimen was standard and the strength of individual agents (usually from the same class) was similar. Neither of these assumptions is valid any longer.

This is because there now exists the opportunity to reduce drug dosages due to favourable pharmacokinetics.

For instance, the anti-HIV drug ritonavir significantly increases indinavir serum levels allowing a reduction in dose, when these two drugs are used in a combination, of 83 per cent for ritonavir and 66 per cent for indinavir.

Not only does this reduce overall drug costs (see table, left), it has the added advantage of reducing the dosage frequency and appears to reduce adverse events such as kidney stones, renal colic, nausea and diarrhoea, which have their own costs.

The evolution of HIV resistance suggests it is the number of sequential mutations in HIV required for a combination to fail that is important, along with the rapidity with which the viral load is suppressed to low levels.

This may allow for multiple-drug induction regimens to be reduced to less intense combinations, such as in the treatment of tuberculosis (although early attempts here have failed to maintain antiviral suppression).

Staying up to date with complex pharmacokinetics and interpretation of unpublished data is a difficult task for both the clinician and the pharmacist, and may be even harder for managers with limited understanding of medical issues.

Some examples are given in the table above of the varying costs of drug regimens used in clinical practice in UK centres, although local contracts with pharmaceutical companies and wholesalers can significantly modify the local cost of drugs.

Pharmacists are experts in drug price negotiation. But the introduction of directorates within trusts means the prices of antiretrovirals may be linked with other products from the same company, which can create conflict in the prioritisation of individual drug purchasing.

The usefulness of this trust-level bargaining is uncertain and a change to the French or Canadian system, in which negotiations are carried out at government level rather than locally, might bring equity for all players, rather than helping those with the largest market.

The need for change

There is an urgent need to change the way in which data on antiretroviral usage is collected and presented. Since the cost of a regimen - and more importantly, the overall cost to the NHS - is no longer directly related to the number of antiretroviral agents prescribed, a new paradigm must be developed.

However, most trusts do not have suitably integrated information technology systems or adequate staffing levels to enable appropriate data collection.

This was seen as recently as 1996 when the national prospective monitoring system tried to obtain countrywide information on HIV-related health care costs and uptake of combination therapy.

3Resources should be allocated to more clearly defining the data sets used and establishing the systems to collect, collate and evaluate the most appropriate measures.

Data collection would undoubtedly be made easier by introducing fully integrated hospital information systems, or electronic prescribing packages that can act as an interface between existing pharmacy and clinic or patient administration systems.

Several pharmaceutical companies have made forays into healthcare management systems that may provide the framework for clearer and more appropriate data collection. The information required is usually available within a healthcare unit, but the collation and analysis require financing.

The pharmaceutical industry input into the collection of such data has been to provide the finance for the hardware as well as for the experts trained in data collection. One impetus for this, of course, is its need for post-marketing surveillance and to inform future marketing strategies.

Recently, three large English HIV units have formed the HIV Health Economics Collaboration to evaluate economic issues in the field.

4But this will require observational data from databases reflecting the realworld use and clinical effectiveness of antiretrovirals.

The maintenance of these databases has significant financial implications. But without them it will be difficult to evaluate the true costs and benefits of therapeutic interventions to ensure that limited resources are allocated most usefully.


1 Randomised trial of nicotine patches in general practice: results at one year. Br Med J 1994; 308 (6942): 1,476-7.

2Denial of Treatment. Terrence Higgins Trust 1997.

3 Beck E, Tolley K, Power A et al . The Use and Cost of HIV Service Provision in England in 1996. Pharmacoeconomics 1998; 14 (6): 639-652.

4 Youle M, Trueman P, Simpson K. Health economics in HIV disease: a review of the European literature. Pharmacoeconomics 1999; 15 (Suppl 1): 1-12.

Key points

The assumption by some HAs that a shift from mono to combination drug therapies for HIV results in a proportional increase in drug expenditure, regardless of health gains, is misguided.

Methods of calculating anti-HIV drug expenditure have failed to keep up with changing treatment regimes.

There is an urgent need to change the way data on antiretroviral use is collected and presented to establish the true cost-effectiveness of new drug regimes.