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Monitoring clinical trials—interim data should be publicly available

BMJ 2001; 323 doi: https://doi.org/10.1136/bmj.323.7310.441 (Published 25 August 2001) Cite this as: BMJ 2001;323:441

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Interim data from clinical trials

EDITOR - The opinions expressed by Lilford and colleagues1 regarding
monitoring of clinical trials are very relevant to a current UK trial of
radiotherapy for breast cancer. The international standard fractionation
regimen consists of 50 Gray in 2 Gray fractions on 5 days per week, but
the evidence base for this is tenuous. Many years ago it was suggested
from reviews of treatment of advanced disease and skin metastases that
fewer larger fractions may be more effective against breast cancer2, but
radiotherapists have been reluctant to do this because of fear of
increased late morbidity.

In 1986 two oncology centres embarked on a randomised trial comparing the
standard 50 Gray with two schedules treating 5 times per fortnight, 39
Gray and 42.9 Gray, both in 13 fractions. Interim data were presented in
1994, showing a significantly lower morbidity for the 39/13 schedule:
there was no difference in the rates of local recurrence of carcinoma, but
there had been very few recurrences at that time3. The trial closed in
1998 with 1400 patients enrolled. The schedules were continued as one of
the arms of the multicentre START trial4, in order to obtain larger
numbers and therefore more conclusive results. The trial data were taken
over by the START data-monitoring committee and are being kept secret on
the basis that their publication would prejudice recruitment to START.

The final results of START will not be known for several years; meanwhile
25 fractions remains the standard.
The median follow-up of these 1400 patients is now 8 years. If there is
still no evidence of a significantly higher risk of recurrence from the 13
-fraction schedule and the data were made publicly available,
radiotherapists could reasonably offer women with breast cancer a course
of treatment involving fewer hospital attendances and with less side-
effects, rather than continuing to give the standard 25 fractions while
awaiting results of START. Other cancer patients would also benefit from
the consequent reduction in the workload and therefore shorter waiting
lists in our hard-pressed radiotherapy departments. The points raised by
Lilford and colleagues make a good case that is now time to publicise the
latest data from this trial.

1. Lilford RJ, Braunholtz D, Edwards S, Stevens A. Monitoring
clinical trials - interim data should be publicly available. BMJ
2001;323:441-2 (25 August).

2. Cohen L. Radiation response and recovery. In:Schwarz EE, ed. The
biological Basis of Radiation Therapy. London:Pitman, 1966.

3. Yarnold JR, Bliss JM, Regan J, Broad B, Davison J, Harrington G,
Ebbs SR. Randomised comparison of a 13-fraction schedule with a
conventional 25-fraction schedule of radiotherapy after local excision of
early breast cancer: preliminary analysis. Radiother Oncol 1994;32 suppl
1:S101.

4. START trial management group. Standardization of breast
radiotherapy (START) trial. Clin Oncol 1999;11:145-7.

Competing interests: No competing interests

04 September 2001
J M Henk
hon consultant clinical oncologist
Royal Marsden Hospital Sutton Surrey