Prescriber decisions are increasingly being pressured by a supply of economic information in the form of cost-effectivenessstudies, or similar evaluations, of a range of pharmaceuticals. These have been welcomed by Virginia Bottomley and a set of guidelines for these studies has been drawn up by the Department of Health and the pharmaceutical industry. Such economic studies are now being published in a wide range of journals and are increasingly being used in promotional literature and publicity handouts by the pharmaceutical companies. Many of these studies are using decision trees with which to represent clinical problems and perform analysis of the costs of treatment. This paper reviews the principles and practice of analysis using these techniques, providing guidance on the critical review of such studies

Stewart, A.

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Decision trees andprescriber choicesAlan StewartPSSRU discussion paper 1102November 1994PSSRUPersonal Social ServicesResearch Unitwww.ukc.ac.uk/PSSRU/Downloaded publicationin Acrobat formatThe PSSRU retains thecopyright in this publication.It may be freely distributed asan Acrobat file and on paper,but all quotations must beacknowledged and permissionfor use of longer excerpts mustbe obtained in advance.We welcome comments aboutPSSRU publications. We wouldparticularly appreciate beingtold of any problemsexperienced with electronicversions as otherwise we mayremain unaware of them.Email: pssru_library@ukc.ac.ukThe PERSONAL SOCIAL SERVICES RESEARCH UNIT undertakes social and health care research, supported mainly by the UnitedKingdom Department of Health, and focusing particularly on policy research and analysis of equity and efficiency in community care, long-termcare and related areas — including services for elderly people, people with mental health problems and children in care. The PSSRU wasestablished at the University of Kent at Canterbury in 1974, and from 1996 it has operated from three sites:Cornwallis Building, University of Kent at Canterbury, Canterbury, Kent, CT2 7NF, UKLondon School of Economics, Houghton Street, London, WC2A 2AE, UKUniversity of Manchester, Dover Street Building, Oxford Road, Manchester, M13 9PL, UKThe PSSRU Bulletin and publication lists can be viewed and downloaded from the Unit’s website and are available free from the unit librarian inCanterbury (+44 (0)1227 837773; email pssru_library@ukc.ac.uk).Email: PSSRU@ukc.ac.uk Website: http://www.ukc.ac.uk/PSSRU/DECISION TREES AND PRESCRIBER CHOICESALAN STEWARTAll correspondence to:Alan StewartPSSRUUniversity of Kent at CanterburyCanterburyKent CT2 7NFPSSRU Discussion Paper 1102PSSRU Discussion Paper 1102, last revised 16 November 19941IntroductionPrescriber decisions are increasingly being pressured by a supply of economic information inthe form of cost-effectiveness studies, or similar evaluations, of a range of pharmaceuticals. These have been welcomed by Virginia Bottomley and a set of guidelines for these studieshas been drawn up by the Department of Health and the pharmaceutical industry1.Such economic studies are now being published in a wide range of journals and areincreasingly being used in promotional literature and publicity handouts by thepharmaceutical companies.  Many of these studies are using decision trees with which torepresent clinical problems and perform analysis of the costs of treatment.  One recentexample compared alternative NSAIDS in the treatment of osteoarthritis2.Figure 1The study that constructed the above diagram tells the reader that there is "an expected costfor three months treatment of £89.12 for oral ibuprofen and £54.57 for topical piroxicam gel".Patients w ith  m ild  osteo-arthritisof the superficial jointsTop ica l P iroxicam  ge lS ystem ic Ibupro fenU lcerA m bulatory careA m bulatory careM edica l careM edica l careS urgical care100 ,000100 ,00099,90099,850100150141 .996.0194.664.08 .012.05 .341.34S urgical careH osp italadm iss ionH osp italadm iss ionU lcerN o u lcerN o u lcerIIIIIIIIIIIIIVIVPSSRU Discussion Paper 1102, last revised 16 November 19942Such answers raise the question of what it is that they actually mean and what they can offerto a clinician.  They may appear to be a marketing ploy, but they do offer potential to be usedpositively by clinicians, pharmacists and others involved in pharmaceutical prescribing orpurchasing.Decision AnalysisThese studies are based on the principles of decision analysis and represent given clinicalproblems using a fairly standard diagrammatic representation and notation.  In Figure 1 thelines represent paths through standard treatment options.  The points where a clinician makesa choice between alternatives are represented by an open rectangle.  Where there isuncertainty as to the outcome of an event, such as a treatment involving a possibility ofsuccess or failure, this is represented by an open circle.  The end point of the analysis isshown by a shaded circle.  They lay out a defined and structured set of events that may occurin a defined sequence. This structure incorporates a number of probabilities at various points,defined as chance nodes, which generate cumulative chances of arriving at any particular endpoint in the diagram via a particular discrete path through the defined set of events.  Thesetechniques are not just used in economic analysis, they have also been used in pure clinicaldecision making3.  The tree itself is just a flow diagram that visually represents decisions andoutcomes in a set order.Data SourcesBut where does all the data come from for this analysis?  One source that is often used isexisting results from clinical trials, where decision analysis techniques can be used togenerate retrospective economic evaluations.  This has been done recently in some studiesevaluating antidepressants in the context of the current debate over using SSRIs orTCAs4,5Alternatively, data is often `synthesised' by evaluating a range of existing pieces ofclinical research though a process of literature search and review that may be extended to aPSSRU Discussion Paper 1102, last revised 16 November 19943formal meta-analysis.  This is a valuable procedure, but one that is subject to a number ofpossible biases: if followed it should be performed rigorously and with regard to principleslaid down in the existing literature6, 7.  It is important that the clinical data used is credibleand rigorously constructed.  If there is any doubt about this, the conclusions of economicstudies may be strongly criticised, as shown in a recent exchange of views on one of theantidepressant evaluations referred to earlier8,9.Evaluation and outputsMoving on from this set of probabilities, the carrying out of cost analysis and ultimately cost-effectiveness analysis is the next stage in the evaluation.  While these models calculatecumulative probabilities along their paths they also aggregate the costs incurred at each stageof the process.  Thus each end point has an accumulated probability of a patient arriving atthat discrete point and also an aggregate expected cost for the health care resources utilisedalong the way.  If one then multiplies each of these aggregate expected costs by the associatedprobability, the result is a weighted cost for that particular point: the sum of these weightedcosts is the average expected cost of any patient being entered into the analysis at the firstpoint in the tree.The above process may sound complex or arithmetically tortuous, but in most studies theactual calculation of expected costs will be performed by one of a number of softwarepackages available in the market. The analyst's role is in defining the problem and setting upthe structure for analysis, then supplying the inputs of costs and clinical data.This process therefore generates an average expected cost for all patients starting a course oftreatment.  For a clinician seeking to understand the economic implications of prescribingdecisions, this means that for each patient entering therapy, using the selected treatment, theexpected cost will equal the given figure. Individual patients will vary widely in terms of theirclinical progress and hence their consumption of resources and resulting costs.  This isPSSRU Discussion Paper 1102, last revised 16 November 19944reflected in the decision tree by their completion at different end points. But these variationsare accounted for in the tree by the use of probabilities providing a weighting to eachaggregate set of costs.  Ideally, a decision analysis paper should present not just thiscalculated expected cost, but also the actual costs that will be incurred if patients experiencespecific sets of clinical outcomes.  For example, the paper could list costs for those who are"cured" by the drug without any side-effects or need for repeated courses and for those at theother extreme, who do not respond and hence need other treatments.Therefore the end result, the expected cost, is what we expect to happen if a specifictreatment is chosen and offered as therapy to a representative sample of patients. By repeatingthe analysis for different drugs or therapeutic options, with differing sets of probabilities, wecan evaluate the cost implications of switching from the existing option to one of a range ofalternative therapies.Testing the resultsThese figures should however, be tested and evaluated by performing thorough sensitivityanalysis.  During this process the assumptions in the analysis are tested by systematicallyvarying the values used for key elements in the study which may be sensitive to change.  Thisarea has recently been reviewed10 and some key aspects of its role identified.  For example,one can test for the uncertainty relating to variability in sample data, such as the actualpackage of resources that are used in providing care.  Not all clinicians will treat patients inthe same manner: sensitivity analysis can allow comparisons of costs where differentquantities of specific items are provided.  Or the costs of providing care within a givenfacility may well vary according to the intensity with which the capacity is used.  Theadjustments allowed in sensitivity analysis allow a range of results to be generated that willcover a range of circumstances.There may also be uncertainty as to the evidence used for efficacy: are the results obtained inPSSRU Discussion Paper 1102, last revised 16 November 19945a clinical trial setting generalisable to clinical practice?  By using sensitivity analysis, one canexamine the impact of efficacy at levels that clinicians would expect to see in everydaypractice.Some analyses may go beyond the calculation of costs or cost-effectiveness ratios andintroduce ideas of the quality of life, performing what is called cost-utility analysis11.  Thegeneral principles of criticism described here apply to these studies as well, but they also raisefurther issues on quality of life measurement which are dealt with in the specialistliterature12,13.SummaryBut when the analysis produces an expected cost, what does that figure actually represent?  Itis an estimate of the average cost that will fall on the health services, per patient treated, if avery large number of patients are treated following the treatment pattern suggested in thestudy.  As shown in the decision tree various sub-groups of patients will incur differentfigures for total costs.  But over the whole range of patients, the high and low cost outcomeswill balance out to give the average figure, which is the expected cost.  Clinicians cancompare these figures as part of the process of considering whether they really should switchbetween drugs on the basis of differing prices.  It may well be that giving in to pressures toswitch to lower-price drugs will not actually help health care budgets, regardless of theimpact on patient well-being.So what are the key points to remember when evaluating these decision analysis studies?i. Does the treatment path represent a credible set of events and decisions i.e. canclinicians recognise the decision tree as representing procedures that approximate totheir own practices?PSSRU Discussion Paper 1102, last revised 16 November 19946ii. Is the data used in the study credible and valid for this particular piece of analysis?iii. If it comes from a clinical trial the usual discretion must be exercised before acceptingthe validity of the toleration, efficacy and adverse events figures.iv. If the data is synthesised from available literature, have rigorous meta-analysisprocedures been followed?  Or is the literature search and review guilty of biases,such as careful selection of papers to be used or of `footnote chasing' where the use ofreferences from papers known to the author shapes the final set of papers incorporatedinto the analysis.All the above areas have to be examined by the reader of any economic study presenting adecision tree.  If the study is accepted as having dealt with these points then it may be usefulas a way for clinicians to move towards a more optimal allocation of their prescribingbudgets.  If the reader is unsatisfied with the rigour of the study's design, methodology andanalysis, then its conclusions should be regarded with the same caution and suspicion thatwould be attached to a clinical trial report that did not appear to be methodologicallyrigorous.PSSRU Discussion Paper 1102, last revised 16 November 19947References1. Department of Health (1994) Press release 94/2512. McKell D., Stewart A. (1994) Cost-minimisation analysis comparing topical vssystemic NSAIDS in the treatment of mild osteoarthritis of the superficial joints,British Journal of Medical Economics, 7, 137-146.3. Thornton J.G., Lilford R.J., Johnson N. (1992) Decision analysis in medicine, BritishMedical Journal, 304, 1099-1103.4. Stewart, A. (1994) Antidepressant pharmacotherapy: cost comparison of SSRIs andTCAs, The British Journal of Medical Economics, 7, 67-79.5. Jönsson, B. and Bebbington, P.E. (1994) What price depression? The cost ofdepression and the cost-effectiveness of pharmacological treatment, British Journal ofPsychiatry, 164, 665-673.6. Cooper H. and Hedges L.V. (eds) (1994) The Handbook of ResearchSynthesis,Russell Sage Foundation, New York.7. Glass G.V., McGaw B. and Smith M.L. (1981) Meta-Analysis in Social Research,Sage Publications, Beverley Hills.8. Freemantle N. and Maynard A. (1994) Something rotten in the state of clinical andeconomic evaluations? Health Economics, 3, 63-67.9. Jönsson B. (1994) Economic Evaluation and Clinical Uncertainty: Response toFreemantle and Maynard, Health Economics, 3, 305-307.10. Briggs A., Sculpher M. and Buxton M. (1994) Uncertainty in the economic evaluationof health care technologies: the role of sensitivity analysis Health Economics, 3, 95-104.11. Hatziandreu, E.J., Brown, R.E., Revicki, D.A., Turner, R. Martindale, J.J., Levine, S.and Siegel, J.E. (1994) Cost-utility of maintenance treatment of recurrent depressionwith sertraline versus episodic treatment with dothiepin, Pharmacoeconomics, 5, 3,249-264.12. Bowling, A. (1991) Measuring Health, Open University Press, Buckingham.13. Walker S.R. and Rosser R.M. (1993) Quality of life assessment: key issues in the1990's, Kluwer Academic Publishers, London.

Decision trees and prescriber choices

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