COMMENTARY

New Drugs for Dementia: A Commissioning Nightmare?

In the UK, health authorities have the responsi-bility to commission care for those who live withintheir boundaries. This responsibility will soon passto groups of general practitioners (primary caregroups), who will become the commissioners ofmost secondary care and providers of primary care.

Health authority budgets are not `ring fenced'for particular disciplines or client groups so there isalways competition for the scarce resources. We getrequests for improved diagnostic imaging, newinterventional facilities, more health promotion,more sta� of all grades, and so on. Priorities whichare determined by Central Government such as thewaiting list initiative arrive and skew commission-ing expenditure.

From April 1999, drug budgets for generalpractitioners (GPs) in the UK will no longer beseparate from hospital and community healthservice funds and so what a GP prescribes willhave an impact on what other services can befunded within that primary care group.

New drugs are a nightmare in this complexsystem. We have an idea of those in the licensingpipeline perhaps a year or 18 months ahead. We donot know exactly when they will be licensed, wedo not know what they will cost, nor do we knowhow many patients will be prescribed them. Thus,patient concerns may push a drug (such as recom-binant Factor VIII for haemophilia) for priorityuse with consequent e�ects on expenditure.

New drugs usually come without su�cientinformation for most health authorities or clin-icians to form a judgement on their place on theprescribing formulary. They have been assessed fore�cacy and safety by the licensing authority andare subject to tests on the quality of manufacture.But how cost-e�ective is a new drug? If the trials (asis the case with donepezil) are on patients with noco-morbidity or co-therapy, how will the drugwork in the `real world' of the patients withmultiple illness and on other medications? We donot even have agreed benchmarks for cost-e�ec-tiveness assessment, nor are we likely to. Tools such

as a quality adjusted life years (QUALYs) are usedby health economists but seem of little practical usewhen commissioning decisions need to be made.For example, if we have no measures to allow us todetermine the relative bene®t of spending £25 000in the UK on seven hip replacements, one com-munity nursing health visitor or one cochlearimplant for a deaf child, how can we weigh therelative merits of an investment in treatments forsecondary coronary heart disease preventionagainst cholinesterase inhibitors for treatment ofAlzheimer's disease?

There is a real risk that the present arrangementsare tending to lead to con¯ict between groups ofpatients eager to try a new drug for a hithertohopeless illness, the therapeutic enthusiasts whowant to prescribe, the therapeutic conservativeswho always point to the disasters of the past(clo®brate and thalidomide) and the ®nancialmanagers of a service. What is the way forward?

First, all parties need to recognize that there is ahuge industry behind any new drug which reachesthe licensing stage and this tends to producepolarized views. It also calls for a degree of healthyscepticism. This is borne out by studies of theaverage life of new drugs in therapeutic use, whichhas been shown in the USA and Scandinavia to beabout 6±7 years.

Second, the evaluation of new drugs of practicaltherapeutic use is of paramount importance. Theremay be more work for busy psychogeriatric clinicsto do if they are asked to assess the suitability ofpatients for anti-dementia drugs and to followpatients up to monitor for therapeutic bene®t andside-e�ects. However, this is the price to pay fordeveloping the evidence to support a view on thecost-e�ectiveness of new drugs in practice ratherthan trial.

Third, there is a need for educational respon-sibility and partnership, with those cliniciansevaluating new drugs in practice sharing theirexperience with physicians in the community, whoalso have a duty to listen.

CCC 0885±6230/99/040257±04$17.50Copyright # 1999 John Wiley & Sons, Ltd.

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY

Int. J. Geriat. Psychiatry 14, 257±260 (1999)

Finally, there must be realism. There will belimits to the funds available for expensive newdrugs. Demand will always exceed resource. Thisrealism must extend to our patients. We need todevelop the skills to communicate our uncertaintiesand the di�cult choices we face with our patients

and the wider community. There has been a loss oftrust between patients and doctors in recent yearsand only a growing partnership will redress this.

ROGER JOHNSON

Manchester Health Authority

COMMENT

Clinical Involvement in Anti-Dementia Drug TrialsÐWhy Bother?

The purpose of this article is to outline some of thefactors that clinicians should take into considera-tion when deciding whether or not to becomeinvolved with anti-dementia drug trials.

These are exciting times. The extraordinarygrowth in our knowledge of the fundamentalpathological processes underlying the dementiasmeans that we are now in a position to start con-templating rational treatments to arrest and evenreverse these disorders. Of course, the intricacies ofthe drug development process mean that there issomething of a time lag between the cutting edge ofresearch and the theoretical basis for treatmentscurrently in the process of coming to the market.For example, in Alzheimer's disease themajor focusof therapeutic research is still on compensating forthe observed neurochemical losses, particularlythose found in the cholinergic system. Thisapproach has resulted in the development of anumber of cholinesterase inhibitors with provene�ectiveness in slowing cognitive decline; donepezil(Aricept) is the ®rst of these compounds to be listedin the UK, and a number of other compounds areexpected to join it in the near future.

This is only the beginning of the story so far asdeveloping treatments for dementia is concerned.Other classes of drugs are also being evaluated inAlzheimer's disease, including muscarinic andnicotinic agonists, and agents that act on manyother neuronal systems a�ected in this disorder,such as the glutamatergic, serotonergic, noradren-ergic and peptidergic systems. In the future,

putative treatments will be aimed at preventingamyloid formation or inhibiting its neurotoxice�ects. The e�ects of drug treatments on the courseof other forms of dementia, such as dementia of theLewy body type and vascular dementia, are alsobeginning to be studied. What is certain is that formany years to come there will be a continuing needfor clinical treatment trials in dementia, and as thenumber of drugs requiring evaluation increases, sowill the need for patients and centres willing toparticipate in these trials. However, the properconduct of a clinical treatment trial involves a lot ofwork for the participating centres, and cliniciansneed to give careful thought as to whether or notthey are in a position to take it on.

THE TYPES OF TREATMENT TRIALS

Clinical trials are generally classi®ed into Phases I±IV, with the majority of medical clinicians beinginvolved in Phase II or Phase III studies. Phase IIstudies monitor the drug's potential e�cacy inlimited numbers of patients for short periods oftime. The main purpose is to demonstrate activity,to assess short-term e�cacy and identify appro-priate drug dose ranges. Phase III studies arelarger, usually multinational, and involve theadministration of the drug to a more varied patientpopulation and over a longer period of time, usually6 months for anti-dementia drugs because of thelikelihood of future chronic administration. Here

Copyright # 1999 John Wiley & Sons, Ltd. Int. J. Geriat. Psychiatry 14, 257±260 (1999)

258 COMMENTARY