Clinical Evidence and study designs in Breast Surgery and surgery
The proposed PhD is seeking a highly motivated medical graduate who has previously demonstrated a strong research interest, strong motivation and who is focused on becoming a future clinical academic leader in surgical research. It would be encouraging if the said incumbent has also demonstrated some research track record.
The PhD will teach the candidate to investigate the extent of the existing published evidence in particular areas that merit future investigation in the field and therefore will form the basis of developing a future multicentre randomized controlled clinical trial in which the PhD candidate could potentially become a future co-Chief Investigator.
The methods will cover the Cochrane approach to systematic reviews and will develop protocols on which to base the aims, content and scoring of respective study designs. Scoring tools will be adopted for non-randomised and randomized studies. The systematic reviews will be registered either in the Cochrane or in the PROSPERO international register before data extraction is commenced. Existing systematic reviews will also be scored using the AMSTAR checklist. The incumbent will be taught all aspects of developing high quality systematic reviews in order to propose future study designs.
Other methods to consolidate the basis for a new trial will include national surgeon surveys and developing and conducting patient focus groups. The candidate will also need to develop a national practice questionnaire for health care professionals (HCPs). Qualitative research methods that are well established will be conducted involving purposive patients groups and HCPs.
The areas under investigation have previously been mooted by individual international cancer centres and form the basis for developing robust clinical evidence in the form of an RCT. These are new innovations in thinking regarding the concept of ‘surgical minimization’.
The first of these is developing the evidence base for recommending breast conserving surgery (BCS) after first in-breast cancer recurrence. Currently, the premise of a standard recommended mastectomy is predicated on the inability to administer further whole breast external beam radiotherapy (RT) after initial BCS. However recent evidence from the TARGIT-A/B trial using intra-operative RT (IORT) permits the delivery of IORT after whole breast irradiation. The proposal will be to evaluate existing evidence and to develop the basis for a RCT investigating the new intervention of a second BCS after local in-breast recurrence in conjunction with IORT.
The second area under investigation is the mooted correlation between post-operative wound infection and breast cancer recurrence. This is based on a number of postulated studies but has not become established in surgical thinking. The same principles underlying establishing the evidence base for a RCT will be applied. In this case there will also be a translational aspect that relates to new evidence regarding circulating ‘blood factors’ such as inflammatory gene single nucleotide polymorphisms and circulating cell free DNA that are permissive for cancer recurrences. The possibility that patients with surgical complications could be given aspirin or other anti-inflammatories as a new intervention versus no aspirin would be an exciting new surgical question and builds on the basis of the new ‘Add Aspirin’ MRC clinical trial evaluating the preventative impact of anti-inflammatory agents in all cancers.
1) Ergina PL et al. BMJ 2013; 346:f3011
2) Gentilini O et al. Ann. Surg. Oncol 2012; 19: 3771-3776
3) Vaidya JS et al. The Lancet 2014; 383:603-13
4) Murthy BL et al. BJC 2007; 96: 1211-17
5) Shi QS et al. Cancer 2015; 121:1138-46