719 the clinical consequences of that decision. Nor are we "introducing bias" (a term which we prefer to reserve for imbalance in the data), but only specifying boundaries in an attempt to quantify and build into the statistical design some of the value judgments that the clinician has to make. These judgments involve not only drug costs but all other con’sequences of a given trial result. You are wrong to suggest that all this should be discussed after the trial is over. Unless clinicians fix decision boundaries when their trials are planned, the outcome may well be the "neutral result" for which you unfairly blame the statistician. To paraphrase a well-known African politician, your editorial is a "sour grape of your own inaccount
vention". Department of Pharmacology and Therapeutics, London Hospital Medical College, London E1 2AD
D. M. CHAPUT D. W. VERE
DE
SAINTONGE
numbers of patients, but some of the other drugs are now being tested in multicentre trials. The outstanding problem in the medical treatment of duodenal ulcer is not how to heal the ulcers but how to keep them healed. Unfortunately, there is no established mechanism for ensuring that satisfactory long-term studies are done, and it is left to the pharmaceutical industry (which provides the drugs) to organise such clinical trials. In view of the financial implications for the N.H.S., this type of problem ought to be monitored by the Committee on Safety of Medicines, the Medical Research Council, or some such body. The range of drugs which promote healing of duodenal ulcers indicates that although we know quite a lot about the pathophysiology of duodenal ulcer, we know nothing about the aaiology of the disease. The low rate of healing of duodenal ulcers with placebo in the U.K., compared with other countries, may have important implications for the N.H.S. but it does mean that the U.K. is a good place to test anti-ulcer
drugs.
***Misunderstanding, possibly; sour grapes, never. In commenting on an interesting, but untested, idea we concentrated theory, which is admirably set out in two consecutive contributions in the British Journal of Clinical Pharmacology. If the decision boundaries fixed before a trial begins have to take account of cost and side-effects then drug prices and the frequency and severity of unwanted reactions must be known, and that is just the trouble. Drug prices are not constant (as Dr Chaput de Saintonge and Professor Vere found out), and how, for example, could clinical triallists have picked a suitable a value for practolol before anyone knew what a horrid drug it was?-ED. L. on
the
practicalities
not
Hospital,
Ninewells, Dundee DD2
1UB
K. G. WORMSLEY
the
TESTING ANTI-ULCER DRUGS SIR,-There have lately been dramatic improvements in our capacity to heal duodenal ulcers, advances which have, perhaps, not yet been sufficiently appreciated by the medical profession. At least nine drugs, with apparently different pharmacological properties, have been reported to heal approximately three-quarters of patients with duodenal ulcer within a month or so (see table). Only cimetidine has been studied in sufficient ULCER-HEALING DRUGS
*6 weeks’ treatment.
Ninewells
t2 weeks’
treatment.
tTripotassilum
dicitrato
CIMETIDINE AND MENTAL CONFUSION
StR,—Grimson* and
Dr Delaney and Dr Ravey (Sept. 3, p. describe confusion after treatment with cimetidine. We 512) have seen what we believe to be two more serious reactions to this drug. An otherwise healthy 55-year-old man presented with a long history of abdominal pain and was found, on gastroscopy, to have a duodenal ulcer. He had had no relief with antacids and liquorice derivatives but on cimetidine 200 mg three times a day with 400 mg at night he had rapid relief of symptoms. However, after a week of treatment he felt dizzy and had double vision so he stopped his evening dose and continued on three tablets daily. At routine review after a month’s treatment he was advised to take two tablets at night and omit daytime treatment. About 3 weeks later his wife noted that he was driving erratically’, and on the following day he had an episode of left-arm weakness with severe sudden pain in the left calf with swelling. He became emotionally upset and was kept in bed for 3 days but continued to take cimetidine two tablets at night for 1 week. When seen at a routine follow-up he had no centralnervous-system abnormality but his left calf was swollen, being 4 cm larger than the right, and clinically he had a resolving deep-venous thrombosis. A 65-year-old van driver was put on cimetidine by his general practitioner because of abdominal pain and a history of peptic ulceration. Towards the end of the course he began to have transient bouts of loss of concentration when he would stop speaking and appear confused. On several occasions he lost his way while driving and had to stop to rest. His mental deterioration has continued and he now has considerable memory loss with speech difficulty and confabulation. E.E.G. and brain scan show a lesion in the left parietal area due to a vascular occlusion. The association of symptoms with cimetidine treatment may be fortuitous but in view of these two cases and other reports we feel that symptoms of confusion should be an indication to stop the drug. Craigavon Area Hospital, Craigavon, Co. Armagh BT63 5QQ
T. J. ROBINSON T. O. MULLIGAN
bismuthate. 1 Burland, W. L., Simkins, M. A. (editors) Cimeditine. Oxford, 1977. 2. Bowers,J.,andothersGastroenterology, 1977, 72, 1032. 3. Wetterhus, S., and others Scand. J. Gastroent. 1977, 12, suppl. 43, 4. Ludwig, H. Therapiewoche, 1977, 27, 1664. 5. Davies, W. A., Reed, P. I. Gut, 1977, 18, 78. 6. Butti, A. Personalcommunication. 7. Shreeve, D.R. Postgrad. med.J. 1975, 51, suppl. 5, p. 33. 8. Peterson, W L. Gastroenterology, 1977, 72, 1112. 9. Gibinski, K., and others Gut, 1977, 18, 636.
CIMETIDINE AND RENAL FAILURE p. 33.
SiR,-Grimsonl and Dr Delaney and Dr Ravey (Sept. 3, p. 512) have warned against the use of cimetidine in cases of renal failure.
1. Grimson, T.A. Lancet,
1977, i, 858.
vention". Department of Pharmacology and Therapeutics, London Hospital Medical College, London E1 2AD
D. M. CHAPUT D. W. VERE
DE
SAINTONGE
numbers of patients, but some of the other drugs are now being tested in multicentre trials. The outstanding problem in the medical treatment of duodenal ulcer is not how to heal the ulcers but how to keep them healed. Unfortunately, there is no established mechanism for ensuring that satisfactory long-term studies are done, and it is left to the pharmaceutical industry (which provides the drugs) to organise such clinical trials. In view of the financial implications for the N.H.S., this type of problem ought to be monitored by the Committee on Safety of Medicines, the Medical Research Council, or some such body. The range of drugs which promote healing of duodenal ulcers indicates that although we know quite a lot about the pathophysiology of duodenal ulcer, we know nothing about the aaiology of the disease. The low rate of healing of duodenal ulcers with placebo in the U.K., compared with other countries, may have important implications for the N.H.S. but it does mean that the U.K. is a good place to test anti-ulcer
drugs.
***Misunderstanding, possibly; sour grapes, never. In commenting on an interesting, but untested, idea we concentrated theory, which is admirably set out in two consecutive contributions in the British Journal of Clinical Pharmacology. If the decision boundaries fixed before a trial begins have to take account of cost and side-effects then drug prices and the frequency and severity of unwanted reactions must be known, and that is just the trouble. Drug prices are not constant (as Dr Chaput de Saintonge and Professor Vere found out), and how, for example, could clinical triallists have picked a suitable a value for practolol before anyone knew what a horrid drug it was?-ED. L. on
the
practicalities
not
Hospital,
Ninewells, Dundee DD2
1UB
K. G. WORMSLEY
the
TESTING ANTI-ULCER DRUGS SIR,-There have lately been dramatic improvements in our capacity to heal duodenal ulcers, advances which have, perhaps, not yet been sufficiently appreciated by the medical profession. At least nine drugs, with apparently different pharmacological properties, have been reported to heal approximately three-quarters of patients with duodenal ulcer within a month or so (see table). Only cimetidine has been studied in sufficient ULCER-HEALING DRUGS
*6 weeks’ treatment.
Ninewells
t2 weeks’
treatment.
tTripotassilum
dicitrato
CIMETIDINE AND MENTAL CONFUSION
StR,—Grimson* and
Dr Delaney and Dr Ravey (Sept. 3, p. describe confusion after treatment with cimetidine. We 512) have seen what we believe to be two more serious reactions to this drug. An otherwise healthy 55-year-old man presented with a long history of abdominal pain and was found, on gastroscopy, to have a duodenal ulcer. He had had no relief with antacids and liquorice derivatives but on cimetidine 200 mg three times a day with 400 mg at night he had rapid relief of symptoms. However, after a week of treatment he felt dizzy and had double vision so he stopped his evening dose and continued on three tablets daily. At routine review after a month’s treatment he was advised to take two tablets at night and omit daytime treatment. About 3 weeks later his wife noted that he was driving erratically’, and on the following day he had an episode of left-arm weakness with severe sudden pain in the left calf with swelling. He became emotionally upset and was kept in bed for 3 days but continued to take cimetidine two tablets at night for 1 week. When seen at a routine follow-up he had no centralnervous-system abnormality but his left calf was swollen, being 4 cm larger than the right, and clinically he had a resolving deep-venous thrombosis. A 65-year-old van driver was put on cimetidine by his general practitioner because of abdominal pain and a history of peptic ulceration. Towards the end of the course he began to have transient bouts of loss of concentration when he would stop speaking and appear confused. On several occasions he lost his way while driving and had to stop to rest. His mental deterioration has continued and he now has considerable memory loss with speech difficulty and confabulation. E.E.G. and brain scan show a lesion in the left parietal area due to a vascular occlusion. The association of symptoms with cimetidine treatment may be fortuitous but in view of these two cases and other reports we feel that symptoms of confusion should be an indication to stop the drug. Craigavon Area Hospital, Craigavon, Co. Armagh BT63 5QQ
T. J. ROBINSON T. O. MULLIGAN
bismuthate. 1 Burland, W. L., Simkins, M. A. (editors) Cimeditine. Oxford, 1977. 2. Bowers,J.,andothersGastroenterology, 1977, 72, 1032. 3. Wetterhus, S., and others Scand. J. Gastroent. 1977, 12, suppl. 43, 4. Ludwig, H. Therapiewoche, 1977, 27, 1664. 5. Davies, W. A., Reed, P. I. Gut, 1977, 18, 78. 6. Butti, A. Personalcommunication. 7. Shreeve, D.R. Postgrad. med.J. 1975, 51, suppl. 5, p. 33. 8. Peterson, W L. Gastroenterology, 1977, 72, 1112. 9. Gibinski, K., and others Gut, 1977, 18, 636.
CIMETIDINE AND RENAL FAILURE p. 33.
SiR,-Grimsonl and Dr Delaney and Dr Ravey (Sept. 3, p. 512) have warned against the use of cimetidine in cases of renal failure.
1. Grimson, T.A. Lancet,
1977, i, 858.
