The generalisability of randomised clinical trials : an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer
(2020) In Breast Cancer Research and Treatment 180(1). p.167-176- Abstract
Purpose: None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC). Methods: In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1–T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are... (More)
Purpose: None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC). Methods: In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1–T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years. Results: Overall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (p = 0.015), with smaller tumours (p = 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%, p < 0.001) and less nodal tumour burden (only 1 macrometastasis in 78.8 versus 79.9 versus 87.3%, p = 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time. Conclusions: This interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials.
(Less)
- author
- de Boniface, Jana ; Ahlgren, Johan ; Andersson, Yvette ; Bergkvist, Leif ; Frisell, Jan ; Lundstedt, Dan ; Olofsson Bagge, Roger ; Rydén, Lisa LU and Sund, Malin
- author collaboration
- organization
- publishing date
- 2020-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Breast cancer, Clinical trial, Omission of axillary dissection, Sentinel lymph node biopsy
- in
- Breast Cancer Research and Treatment
- volume
- 180
- issue
- 1
- pages
- 10 pages
- publisher
- Springer
- external identifiers
-
- pmid:31989379
- scopus:85078500324
- ISSN
- 0167-6806
- DOI
- 10.1007/s10549-020-05537-1
- language
- English
- LU publication?
- yes
- id
- 64149891-ac43-45ce-a347-6ff77e5b3ba5
- date added to LUP
- 2020-02-06 14:15:00
- date last changed
- 2024-06-27 12:57:12
@article{64149891-ac43-45ce-a347-6ff77e5b3ba5, abstract = {{<p>Purpose: None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC). Methods: In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1–T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years. Results: Overall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (p = 0.015), with smaller tumours (p = 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%, p < 0.001) and less nodal tumour burden (only 1 macrometastasis in 78.8 versus 79.9 versus 87.3%, p = 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time. Conclusions: This interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials. </p>}}, author = {{de Boniface, Jana and Ahlgren, Johan and Andersson, Yvette and Bergkvist, Leif and Frisell, Jan and Lundstedt, Dan and Olofsson Bagge, Roger and Rydén, Lisa and Sund, Malin}}, issn = {{0167-6806}}, keywords = {{Breast cancer; Clinical trial; Omission of axillary dissection; Sentinel lymph node biopsy}}, language = {{eng}}, number = {{1}}, pages = {{167--176}}, publisher = {{Springer}}, series = {{Breast Cancer Research and Treatment}}, title = {{The generalisability of randomised clinical trials : an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer}}, url = {{http://dx.doi.org/10.1007/s10549-020-05537-1}}, doi = {{10.1007/s10549-020-05537-1}}, volume = {{180}}, year = {{2020}}, }