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fluid (1-1-5 5 g/1) is likely to reduce the risk of hypoglycaemicaccidents.

Service de Reanimation, Groupe HospitalierPitié-Salpétrière, Paris 75013 K. SAMII

Centre d’Hémodialyse Edouard Rist,14 rue Boileau, Paris 75016 CH. CIANCIONI

Service de Néphrologie, Groupe HospitalierPitié-Salpétrière, Paris 75013

J. ROTTEMBOURGF. BISSELICHES

C. JACOBS

DOUBLE-BLIND TRIALS

SIR,-We welcome and support the findings of Dr Hill andher colleagues (Feb. 14, p. 352). Like them we have followedJoyce’s lead, but in two ways:

(1) When a trial is still in the design stage, we always havea "placebo tasting session" when a "blind" group triesto distinguish drug from dummy.

(2) During trials the observers, whether they be doctorsmaking clinical observations or patients completingdiary cards, are asked to try to break the code by notingwhich remedy they think is being provided at each clinicvisit.

The reason for the second procedure is that blindness cannever be assumed, as Dr Hill and others show, so the trialistmust either improve placebo matching until it is perfect, whichis impossible, or measure its imperfection, which can be done.We therefore collect doctors’ or patients’ views on their medi-cation and analyse them statistically.

Inevitably the distribution of these views about the identityof the treatments is not completely random. Two importantquestions follow: how much bias is associated with a givendegree of code breaking, and how will this bias alter the treat-ment outcome? We are still looking for the answers and for themoment content ourselves with accepting only small depar-tures from randomness as likely to affect the trial adversely.

These practices have led us into some amusing experiences,and have failed on some occasions. For example in one trial ofinjected gold for rheumatoid disease, a perfect placebo matchwas obtained at the start of the trial, but was lost a few weekslater when the gold solution turned yellow while the placeboremained white. In another trial a patient found that he couldbreak a nearly perfect match by scratching the tablets lightlywith his finger nail. One set developed a sheen when held upto the light, the other did not. An anaesthetist found that hecould distinguish autoclaved from filtered dextrose solutions bylistening as the needle went in; autoclaved bottles emit a softhiss. One pharmaceutical company kindly supplied a beauti-fully matched set of drug and placebo ampoules, but the word"placebo" was printed on half of them!

However, it is very satisfying to find that subjects cannotbreak a code; that is the final test. Even medical students seemunable to decode trinitrin set in the hollow of ’Polo’ mints withhard icing sugar.

Perfectly matching treatments can also cause problems. Inmany diseases (especially those associated with pain) the pa-tient’s expectations are important determinants of the treat-ment outcome. If the patient gets benefit from the first of aseries of identical treatments the beneficial effect may carryover into successive treatment periods, the patient believing histherapy to be unchanged. This effect may be avoided by mak-ing the treatment distinctive and telling the patient that theyare all different. This is in effect a "double dummy" approach,one dummy being for the drug, the other for the emotional im-pact of its appearance. In a recent trial (unpublished) of threeantacids in duodenal ulceration it became clear that the tasteof one of the treatments could not easily be disguised or

matched in the placebo. Furthermore the trial consisted of 24

1. Joyce, C. R. B. in Psychopharmacology Dimensions and Perspectives (editedby M. Balint); p. 215. London, 1968.

treatment periods of one day each, so carry-over effects couldbe serious. They were avoided by packing each treatment infoil packs of a distinctive colour and telling the patients thatthree different tablets were being tested. To preserve the clini-cians’ blindness the correspondence between colour of the

packs and their contents was varied from patient to patient.This approach may, however, encourage the development ofbias as the trial progresses.

Whichever way the problem of blindness is approached themeasurement of bias and its implications still constitutes thecore of uncertainty in the apple of the best-planned clinicaltrial. The benefits of the double-blind trial have been welldemonstrated. Progress is likely to come from better methodsto measure bias than from a return from double-blindness tothe greater bias which preceded it.Clinical Trials Unit,Department of Pharmacologyand Therapeutics,London Hospital Medical College,E1 2AD

D. W. VERE

D. M. CHAPUT DE SAINTONGE

FLUPHENAZINE DECANOATE

SIR,- Your editorial does less than justice to the advan-tages of slow-release injections in the maintenance treatmentof schizophrenia. I am concerned lest young psychiatrists andothers involved in the management of these patients infer thatthere is some special therapeutic benefit implicit in prolongedinstitutional care as opposed to current, albeit imperfect, com-munity methods based upon chemotherapy. You seem to com-mend a lukewarm attitude towards discharge from hospital un-less and until funds and other resources for hostels, shelteredworkshops, and the like are forthcoming. I believe that such

equivocation will not only cause patients, families, and staff to

lose heart, but also, in the broader perspective, remove thestimulus necessary to elicit the funds needed for these com-munity facilities. Few would wish to put the clock back to theasylum pattern of care. Surely the "quality of life" in the realworld is preferable to that of an institution, however well-in-tentioned ?

Many would agree that schizophrenia is a condition withsocial implications and that there have been considerable

advances, notably by the Maudsley M.R.C. Social PsychiatryUnit, of our understanding of the ways in which these in-fluence prognosis. Of course, such factors have to be consid-ered before discharge of the patient. Nevertheless, schizo-

phrenia is also a disease (or diseases) suffered by patients, andmedical models of care are apposite.Good or bad outcome patients, irrespective of whether they

are discharged on drugs or not, cannot yet be reliably pre-dicted but only known post hoc. However, many patients withdiscrete psychoses of excellent outcome would be spared the in-convenience of long-term depot injections if a careful clinicaldistinction between affective illness and schizophrenia weremade, and if this form of treatment were reserved for thesecond and subsequent admissions to hospital.Much about depot fluphenazine and flupenthixol is still un-

clear-especially, the duration and dose of maintenance

therapy, whether they can ever safely be withdrawn, and theprevention and reversibility of extrapyramidal symptoms.Answers will appear in time, but meanwhile there is littledoubt that over the ten years these preparations have beenavailable, they have been overwhelmingly a force for goodCertainly the many schizophrenics now maintained on them,who are reintegrated and resettled in society, would acknow-ledge this.Northwick Park Hospital andClinical Research Centre,Watford Road, Harrow,Middlesex HA1 3UJ M. W. P. CARNEY

1. Lancet, 1975, ii, 1193.