- Email: [email protected]
This is the first study
Correspondence
Women
Men
CEA Number randomised Mean years of follow-up Immediate hazard of stroke or death Other first events (annual risk)† Nature of events Non-perioperative stroke Vertebrobasilar or haemorrhagic Cardioembolic Other Perioperative stroke (after deferred CEA)‡
Deferral
CEA
This is the first study
Both sexes Deferral
CEA
Deferral
539 537 1021 1023 1560 1560 3·83 3·94 3·87 3·83 3·86 3·87 18/483 (3·7%) 23/961 (2·4%) ·· 41/1444 (2·8%) ·· 16 (0·8%) 43 (2·0%) 35 (0·9%) 106 (2·7%) 51 (0·8) 149 (2·5)
2 4 10 -
4 2 33 4/91
10 3 22 -
18 6 75 7/169
12 7 32 -
22 8 108 11/260
CEA=carotid endarterectomy. *Patients contribute to analyses only until their first such event. †Includes 1 woman and 5 men who were allocated immediate CEA but then had a stroke before CEA was undertaken. ‡Number and denominator exclude those with stroke before CEA.
Table: Stroke (or perioperative death) within 6 years of randomisation into ACST, by sex and treatment allocation*
tically stable overall results from ACST rather than the less stable subgroup results. This proposal remains appropriate even when, as for women, the relevant subgroup involves about a third of the whole study (and is even more appropriate when, as for those on anticoagulants at entry, the subgroup involves only a few percent of the whole study population). Nevertheless, as an example, the table describes the ACST results separately for women only (a much discussed subgroup), for men only, and for both sexes together. For Women
Event-free
100
95
Immediate 7·8% (SE 1·3)
90 Deferred 11·8% (SE 1·8) 85
Women: 6-year difference 4·0% (SE 2·2), p=0·07 0
Number at risk Immediate 539 Deferred 537
Men
1
2
3
4
5
6
480 486
416 417
353 372
298 314
244 254
185 188
Event-free
100
95
Immediate 7·4% (SE 1·0)
90
Deferred 13·9% (SE 1·3)
85
Men: 6-year difference 6·6% (SE 1·6), p=0·0001
0 Number at risk Immediate 1021 Deferred 1023
1
2
3 Years
4
5
6
920 924
800 805
686 687
582 569
452 458
341 338
Figure: Kaplan-Meier estimates of the proportions of women and men who would be free of stroke (or perioperative death) at various times, in the absence of other causes of death: updated 6-year ACST results
1126
the table we used the latest update of the ACST results, so it includes a few more months of follow-up than did our original report. In the table, women have a risk of 3·7% from immediate carotid endarterectomy (95% CI 2·2–5·9), and benefit by 1·25% per year (or slightly more, if the woman who had a stroke 6 months after randomisation but before surgery is excluded). The annual benefit is significant (p= 0·0004), but has a relatively wide 95% CI of 0·55–1·95. If among women a hazard of 3·7% is followed by benefit of 1·25% per year then the curves (figure) will meet at about 3 years for women, as opposed to 1·5 years for men. However, if the perioperative hazard for women had been taken to be 5% then the curves would have taken about 4 years to meet. Although the 6-year net benefit is seperately significant only for men, it is not significantly different for men and women (especially if, to meet the correspondents’ concerns about mechanisms or chance imbalances in unrelated abnormalities, the analyses exclude strokes classified as cardioembolic, vertebrobasilar, or haemorrhagic). Reliable assessment of the longer-term net benefit for women, for men, and for both sexes will, of course, depend on followup of the stroke incidence rates for several more years—ie, until well after the curves have crossed over.
ACST Writing Committee, on behalf of the ACST Collaborative Group [email protected]
As is my habit, for a recent plane trip I packed a grocery bag with unread journals for catch-up reading. On the plane, I skim the articles and tear out selected papers for later careful reading (often wishfully). By the time I have reached my destination the grocery bag is filled with the remainder for discarding. On this particular trip I was struck by the times I came across words such as “this is the first study” or “to the best of our knowledge this is the first study”. I spent some time thinking about why investigators seem so compelled to stake superlative claims, but I could not come up with a satisfactory explanation. It seems to me that such claims have less to do with the actual science and a result’s validity, and more to do with the cleverness and insight of the investigators. Yet the latter are generally evident from reading the report. Or could it be an attempt by researchers to emphasise and add importance to their work? It might be interesting to study such published claims and see how many turn out to be true, even the “we are unaware” ones; it takes only one black swan. In the absence of such a study, I would prefer to see those claims omitted and to let the design, data, analyses, and conclusions speak for themselves. Leave it to the editorialists and time to determine which study was the first.
Mark D Grant [email protected] 4907 S Kimbark Avenue, Chicago, IL 60615, USA
Department of Error Weir REP, Whitehead DEJ, Zaidi FH, Greaves BBG. Pupil blown by a puffer. Lancet 2004; 364: 415—In this Correspondence letter (July 31, p 415), reference 1 and the text associated with it should have been deleted.
www.thelancet.com Vol 364 September 25, 2004
Women
Men
CEA Number randomised Mean years of follow-up Immediate hazard of stroke or death Other first events (annual risk)† Nature of events Non-perioperative stroke Vertebrobasilar or haemorrhagic Cardioembolic Other Perioperative stroke (after deferred CEA)‡
Deferral
CEA
This is the first study
Both sexes Deferral
CEA
Deferral
539 537 1021 1023 1560 1560 3·83 3·94 3·87 3·83 3·86 3·87 18/483 (3·7%) 23/961 (2·4%) ·· 41/1444 (2·8%) ·· 16 (0·8%) 43 (2·0%) 35 (0·9%) 106 (2·7%) 51 (0·8) 149 (2·5)
2 4 10 -
4 2 33 4/91
10 3 22 -
18 6 75 7/169
12 7 32 -
22 8 108 11/260
CEA=carotid endarterectomy. *Patients contribute to analyses only until their first such event. †Includes 1 woman and 5 men who were allocated immediate CEA but then had a stroke before CEA was undertaken. ‡Number and denominator exclude those with stroke before CEA.
Table: Stroke (or perioperative death) within 6 years of randomisation into ACST, by sex and treatment allocation*
tically stable overall results from ACST rather than the less stable subgroup results. This proposal remains appropriate even when, as for women, the relevant subgroup involves about a third of the whole study (and is even more appropriate when, as for those on anticoagulants at entry, the subgroup involves only a few percent of the whole study population). Nevertheless, as an example, the table describes the ACST results separately for women only (a much discussed subgroup), for men only, and for both sexes together. For Women
Event-free
100
95
Immediate 7·8% (SE 1·3)
90 Deferred 11·8% (SE 1·8) 85
Women: 6-year difference 4·0% (SE 2·2), p=0·07 0
Number at risk Immediate 539 Deferred 537
Men
1
2
3
4
5
6
480 486
416 417
353 372
298 314
244 254
185 188
Event-free
100
95
Immediate 7·4% (SE 1·0)
90
Deferred 13·9% (SE 1·3)
85
Men: 6-year difference 6·6% (SE 1·6), p=0·0001
0 Number at risk Immediate 1021 Deferred 1023
1
2
3 Years
4
5
6
920 924
800 805
686 687
582 569
452 458
341 338
Figure: Kaplan-Meier estimates of the proportions of women and men who would be free of stroke (or perioperative death) at various times, in the absence of other causes of death: updated 6-year ACST results
1126
the table we used the latest update of the ACST results, so it includes a few more months of follow-up than did our original report. In the table, women have a risk of 3·7% from immediate carotid endarterectomy (95% CI 2·2–5·9), and benefit by 1·25% per year (or slightly more, if the woman who had a stroke 6 months after randomisation but before surgery is excluded). The annual benefit is significant (p= 0·0004), but has a relatively wide 95% CI of 0·55–1·95. If among women a hazard of 3·7% is followed by benefit of 1·25% per year then the curves (figure) will meet at about 3 years for women, as opposed to 1·5 years for men. However, if the perioperative hazard for women had been taken to be 5% then the curves would have taken about 4 years to meet. Although the 6-year net benefit is seperately significant only for men, it is not significantly different for men and women (especially if, to meet the correspondents’ concerns about mechanisms or chance imbalances in unrelated abnormalities, the analyses exclude strokes classified as cardioembolic, vertebrobasilar, or haemorrhagic). Reliable assessment of the longer-term net benefit for women, for men, and for both sexes will, of course, depend on followup of the stroke incidence rates for several more years—ie, until well after the curves have crossed over.
ACST Writing Committee, on behalf of the ACST Collaborative Group [email protected]
As is my habit, for a recent plane trip I packed a grocery bag with unread journals for catch-up reading. On the plane, I skim the articles and tear out selected papers for later careful reading (often wishfully). By the time I have reached my destination the grocery bag is filled with the remainder for discarding. On this particular trip I was struck by the times I came across words such as “this is the first study” or “to the best of our knowledge this is the first study”. I spent some time thinking about why investigators seem so compelled to stake superlative claims, but I could not come up with a satisfactory explanation. It seems to me that such claims have less to do with the actual science and a result’s validity, and more to do with the cleverness and insight of the investigators. Yet the latter are generally evident from reading the report. Or could it be an attempt by researchers to emphasise and add importance to their work? It might be interesting to study such published claims and see how many turn out to be true, even the “we are unaware” ones; it takes only one black swan. In the absence of such a study, I would prefer to see those claims omitted and to let the design, data, analyses, and conclusions speak for themselves. Leave it to the editorialists and time to determine which study was the first.
Mark D Grant [email protected] 4907 S Kimbark Avenue, Chicago, IL 60615, USA
Department of Error Weir REP, Whitehead DEJ, Zaidi FH, Greaves BBG. Pupil blown by a puffer. Lancet 2004; 364: 415—In this Correspondence letter (July 31, p 415), reference 1 and the text associated with it should have been deleted.
www.thelancet.com Vol 364 September 25, 2004