Current Medical Research and Opinion
Vol. 5 , No. 7, 1978
Diflunisal in general practice
E. C. Huskisson, M.D., M.R.C.P.. T. N. Williams,* B.Sc., M.I.S., L. D. Shaw,* B.Sc., and
J. Kerry* Curr Med Res Opin Downloaded from informahealthcare.com by Washington University Library on 01/03/15 For personal use only.
Sr. Bartholomew's Hospital, London, and *Merck Sharp & Dohmf Ltd.,
Hoddesdon, England Curr. Med. Res. Opin., (1978), 5, 589.
Paper read: 19th June 1978
Summary A large-scale, double-blind comparative study was carried out in general practice to assess the relative efficacy and tolerance of diflunisal and aspirin in patients suffering ,from acute painful conditions such as sprains and strains, osteoarthritis, etc. Patients received either 250 mg or 500 mg diflunisal twice daily, or 600 mg aspirin 4-times daily for 5 days. The results of subjective assessments ofpain relief from the daily records of 1902patients (967 on dijlunisal, 935 on aspirin), and the overall assessment ojresponse by both doctors and patients, showed that diflunisal was significantly better than aspirin. Gastric side-efects were more common and more severe in patients receiving ospirin, and more often led to withdrawal of treatment. Key words: Diflunisal - aspirin - sprains and strains - osteoarthritis
Introduction Drugs should be tested in a setting as close as possible to that in which they are used. Most trials take place in hospitals, but most drugs are used in general practice. This study was an attempt to assess diflunisal, used as a simple analgesic, in general practice using scientifically acceptable trial methodology. The trial was controlled, comparing diflunisal and aspirin, and an attempt was made to obscure the nature of the medication in any particular patient.
Patients and methods A total of 500 general practitioners throughout the U.K. were each asked to select 5 patients who had acute pain for which a simple analgesic would normally be prescribed. The age and sex of thepatients, site and cause ofpain, initial pain severity, concomitant illness and concomitant medication were recorded before the start of the study. Each general practitioner treated his trial patients with only one of the test drugs, diflunisal or aspirin, and all the participating doctors in a particular area gave the same treatment to avoid any comparison by patients or doctors of the tablets or instructions. Diflunisal was supplied as peach-coloured, pillow-shaped tablets (250 mg) to be taken in an initial dose of 500 mg, then either 250 or 500 mg twice 589
Curr Med Res Opin Downloaded from informahealthcare.com by Washington University Library on 01/03/15 For personal use only.
Diflunisal in general practice
daily depending on response. Aspirin, called ‘DQ 174’ to obscure its nature, was supplied aspink tablets (300 mg) to be taken in a dosage of up to 600 mg 4-times daily. During the study, patients were asked to complete a daily record of pain relief, using a 5-point descriptive scale, and to make a note of the number of tablets they had taken. At the end of the 5-days’ treatment period both patient and doctor made a global assessment of response, using a 5-point descriptive scale. The patients were asked a standard question: “Has the treatment upset you in any way?”. Side-effects elicited in this way were recorded with their severity. In patients who failed to complete 5 days of treatment, the reasons were recorded.
Results Of the 1902 patients whose records were analyzed, 967 received diflunisal and 935 received aspirin. The two groups were well matched for age, sex, and initial pain severity. Table I gives details of the site and cause of pain, and of any concomitant illness and therapy in the total patient population. Table I. Site and cause of pain, and any concomitantillness and treatment in 1902 patients studied Patient details
% total no. patients
Site ofpain Back Shoulders Neck Knees Head Others
30 14 11 10 5 30
Cause of pain Sprains and strains Osteoarthritis Trauma Other painful conditions, e.g. shingles, neuralgia, toothache, fibrositis, etc. Unknown Concomitant illness None Hypertension Depression Peptic ulcer Bronchitis Others Concomitant therapy None Anti-hypertensive Antirheumatic Antidepressant Antacid Others
590
19 14 10 45 12 79.0 3.1 2.0 1.6 1.4 12.3 74.5 5.5
2.1 1.7 0.6
15.6
E. C. Huskisson, T. N. Williams, L. D. Shaw and J. Kerry
Curr Med Res Opin Downloaded from informahealthcare.com by Washington University Library on 01/03/15 For personal use only.
The commonest sites of pain were the back, shoulders, neck and knees, and the commonest causes were sprains and strains, and osteoarthritis. It is clear that musculo-skeletal problems formed a very large part of this group of patients who required simple analgesics. Most of the patients had no other illness and were not taking any other treatment. Patients’ assessment The patients’ daily assessment of pain relief showed that diflunisal was slightly more effective than aspirin at all times. Both drugs took a few days to exert their maximum effect. Table I1 shows the number of tablets of diflunisal or aspirin taken by patients on each of the 5 days of the study. Approximately equal numbers of patients took 2 (250 mg b.d.) and 4 (500 mg b.d.) tablets of diflunisal daily. Most of the patients on aspirin continued to take 8 tablets (2.4 g) daily. Table 11. Number of tablets of diflunisal and aspirin taken on each day of study: percentage of patients
No. tablets per day
Day 1
Diflunisal group 2 46.3 3 15.5 4 34.6
Day 2
Day 3
Day 4
Day 5
34.8 16.8
36.2 15.1 44.9
31.1 13.5
40.5
45.5
11.9 42.9
4.7 9.9 83.5
5.3 12.2 79.9
8.2 11.6 16.5
45.5
Aspirin group
4 6 8
20.3 19.8 51.9
4.4 9.9 83.1
Note: various other numbers of tablets per day were taken by the remaining patients
0verall assessment Doctors’ and patients’ assessments of response after 5-days’ treatment are summarized in Table 111. In both assessments, diflunisal was significantlybetter than aspirin. Table 111. Patients’ and doctors’ overall assessment of response to treatment: percentage of patients
Response
Excellent Good Fair Poor None Significance of difference in favour of diflunisal
Patients’ assessment
Doctors’ assessment
Diflunisal
(n=967)
Aspirin (n =935)
Diflunisal (n =961)
(n=930)
11.6 39.4 25.6 14.1 9.3
12.0 34.9 22.9 18.9 11.2
11.7 39.6 26.2 14.1 7.9
12.1 34.8 24.2 19.1 9.8
xz =12.5, p
Vol. 5 , No. 7, 1978
Diflunisal in general practice
E. C. Huskisson, M.D., M.R.C.P.. T. N. Williams,* B.Sc., M.I.S., L. D. Shaw,* B.Sc., and
J. Kerry* Curr Med Res Opin Downloaded from informahealthcare.com by Washington University Library on 01/03/15 For personal use only.
Sr. Bartholomew's Hospital, London, and *Merck Sharp & Dohmf Ltd.,
Hoddesdon, England Curr. Med. Res. Opin., (1978), 5, 589.
Paper read: 19th June 1978
Summary A large-scale, double-blind comparative study was carried out in general practice to assess the relative efficacy and tolerance of diflunisal and aspirin in patients suffering ,from acute painful conditions such as sprains and strains, osteoarthritis, etc. Patients received either 250 mg or 500 mg diflunisal twice daily, or 600 mg aspirin 4-times daily for 5 days. The results of subjective assessments ofpain relief from the daily records of 1902patients (967 on dijlunisal, 935 on aspirin), and the overall assessment ojresponse by both doctors and patients, showed that diflunisal was significantly better than aspirin. Gastric side-efects were more common and more severe in patients receiving ospirin, and more often led to withdrawal of treatment. Key words: Diflunisal - aspirin - sprains and strains - osteoarthritis
Introduction Drugs should be tested in a setting as close as possible to that in which they are used. Most trials take place in hospitals, but most drugs are used in general practice. This study was an attempt to assess diflunisal, used as a simple analgesic, in general practice using scientifically acceptable trial methodology. The trial was controlled, comparing diflunisal and aspirin, and an attempt was made to obscure the nature of the medication in any particular patient.
Patients and methods A total of 500 general practitioners throughout the U.K. were each asked to select 5 patients who had acute pain for which a simple analgesic would normally be prescribed. The age and sex of thepatients, site and cause ofpain, initial pain severity, concomitant illness and concomitant medication were recorded before the start of the study. Each general practitioner treated his trial patients with only one of the test drugs, diflunisal or aspirin, and all the participating doctors in a particular area gave the same treatment to avoid any comparison by patients or doctors of the tablets or instructions. Diflunisal was supplied as peach-coloured, pillow-shaped tablets (250 mg) to be taken in an initial dose of 500 mg, then either 250 or 500 mg twice 589
Curr Med Res Opin Downloaded from informahealthcare.com by Washington University Library on 01/03/15 For personal use only.
Diflunisal in general practice
daily depending on response. Aspirin, called ‘DQ 174’ to obscure its nature, was supplied aspink tablets (300 mg) to be taken in a dosage of up to 600 mg 4-times daily. During the study, patients were asked to complete a daily record of pain relief, using a 5-point descriptive scale, and to make a note of the number of tablets they had taken. At the end of the 5-days’ treatment period both patient and doctor made a global assessment of response, using a 5-point descriptive scale. The patients were asked a standard question: “Has the treatment upset you in any way?”. Side-effects elicited in this way were recorded with their severity. In patients who failed to complete 5 days of treatment, the reasons were recorded.
Results Of the 1902 patients whose records were analyzed, 967 received diflunisal and 935 received aspirin. The two groups were well matched for age, sex, and initial pain severity. Table I gives details of the site and cause of pain, and of any concomitant illness and therapy in the total patient population. Table I. Site and cause of pain, and any concomitantillness and treatment in 1902 patients studied Patient details
% total no. patients
Site ofpain Back Shoulders Neck Knees Head Others
30 14 11 10 5 30
Cause of pain Sprains and strains Osteoarthritis Trauma Other painful conditions, e.g. shingles, neuralgia, toothache, fibrositis, etc. Unknown Concomitant illness None Hypertension Depression Peptic ulcer Bronchitis Others Concomitant therapy None Anti-hypertensive Antirheumatic Antidepressant Antacid Others
590
19 14 10 45 12 79.0 3.1 2.0 1.6 1.4 12.3 74.5 5.5
2.1 1.7 0.6
15.6
E. C. Huskisson, T. N. Williams, L. D. Shaw and J. Kerry
Curr Med Res Opin Downloaded from informahealthcare.com by Washington University Library on 01/03/15 For personal use only.
The commonest sites of pain were the back, shoulders, neck and knees, and the commonest causes were sprains and strains, and osteoarthritis. It is clear that musculo-skeletal problems formed a very large part of this group of patients who required simple analgesics. Most of the patients had no other illness and were not taking any other treatment. Patients’ assessment The patients’ daily assessment of pain relief showed that diflunisal was slightly more effective than aspirin at all times. Both drugs took a few days to exert their maximum effect. Table I1 shows the number of tablets of diflunisal or aspirin taken by patients on each of the 5 days of the study. Approximately equal numbers of patients took 2 (250 mg b.d.) and 4 (500 mg b.d.) tablets of diflunisal daily. Most of the patients on aspirin continued to take 8 tablets (2.4 g) daily. Table 11. Number of tablets of diflunisal and aspirin taken on each day of study: percentage of patients
No. tablets per day
Day 1
Diflunisal group 2 46.3 3 15.5 4 34.6
Day 2
Day 3
Day 4
Day 5
34.8 16.8
36.2 15.1 44.9
31.1 13.5
40.5
45.5
11.9 42.9
4.7 9.9 83.5
5.3 12.2 79.9
8.2 11.6 16.5
45.5
Aspirin group
4 6 8
20.3 19.8 51.9
4.4 9.9 83.1
Note: various other numbers of tablets per day were taken by the remaining patients
0verall assessment Doctors’ and patients’ assessments of response after 5-days’ treatment are summarized in Table 111. In both assessments, diflunisal was significantlybetter than aspirin. Table 111. Patients’ and doctors’ overall assessment of response to treatment: percentage of patients
Response
Excellent Good Fair Poor None Significance of difference in favour of diflunisal
Patients’ assessment
Doctors’ assessment
Diflunisal
(n=967)
Aspirin (n =935)
Diflunisal (n =961)
(n=930)
11.6 39.4 25.6 14.1 9.3
12.0 34.9 22.9 18.9 11.2
11.7 39.6 26.2 14.1 7.9
12.1 34.8 24.2 19.1 9.8
xz =12.5, p
