Aplicabilidad de las estrategias del Plan

UK’s submission for the INTRABEAM Photon Radiotherapy

System for early breast cancer Multiple Technology Appraisal

Comprehensiveness of ascertainment of published studies

Clinical effectiveness

The MS contains a narrative summary of the key RCT and other studies (non-randomised) with the results of each study presented separately. One table is presented in the executive summary detailing nine studies reporting on cosmesis and toxicity. Tables of patient and tumour characteristics are presented separately for each included study in Appendix 1. There is no formal systematic review of clinical effectiveness evidence although a systematic literature search is described.

l Were databases and dates of searches specified?

¢ Yes, pages 6 and 7 report that three databases were searched up to December 2013, with literature included only from 2007 onwards.

l Were search strategies supplied?

¢ Yes.

l Was enough detail provided to be reproducible?

¢ Yes.

l Did they search/report on ongoing studies?

¢ No searches for ongoing studies are reported.

l Did they search for conference proceedings?

¢ Unclear– conference proceedings may have been included in the three databases searched but this is not specifically stated. Information is included from some conference posters.

l How many of the data are commercial in confidence/academic in confidence?

Searches identified

l Note the number of studies.

¢ The MS does not state how many citations were identified by the search. The MS does not describe the processes or criteria (other than‘related to the subject to be evaluated’) for selecting included studies. The MS does not state how many studies overall have been included in the submission. The reviewer has identified 26 studies, of which six are described as poster abstracts.

l Note what study types.

¢ The MS does not consistently identify the study types for the studies included in the review. Only one RCT is included, the majority of the remaining 25 citations appear to be cohort studies.

l Did these meet our inclusion criteria?

¢ The included RCT meets our inclusion criteria as do the studies reporting on subgroups of TARGIT-A participants. The remaining studies included in the MS did not meet our inclusion criteria, chiefly on the grounds of study design.

l Were any studies identified that we have not included?

¢ No.

l Any key details/issues?

¢ No.

Clinical analysis

l Any major differences in evidence reported?

¢ The MS discusses evidence from four articles that are all based on the key TARGIT-A trial and which are also included in the SHTAC’s systematic review. The MS has not included evidence from the initial TARGIT-A trial publication from 201064_{stating that this is because more recent data are}

available and the 2010 results are expected to be included in the most recent (2014) publication.65

The SHTAC’s systematic review does include evidence on early complications from the 2010 TARGIT-A trial publication as these are not reported by the more recent 2014 trial paper. The MS also does not include a study published by Sperk et al.67_{reporting on long-term toxicity following treatment either}

with the INTRABEAM (n= 54) device or WB-EBRT (n = 55) at one trial centre in Mannheim, Germany. The MS does, however, include a cohort study79_{that reports on post-operative complications within}

the first week following surgery among 208 patients treated with INTRABEAM at a centre in

Mannheim, Germany, who were participating in the TARGIT-A trial. Tuschy et al.79_{is excluded from the}

SHTAC’s systematic review because it is likely that the data reported are either partially or wholly contained within the early complications reported by the initial TARGIT-A trial publication64_{and, in}

addition, Tuschy et al.79_{report no comparable data for the WB-EBRT group.}

¢ The MS also discusses evidence from n= 22 studies (six only reported as conference abstracts) that did not meet the inclusion criteria of the SHTAC’s review.

¢ The MS provides a narrative summary for each individual study that has been included. Individual tables of baseline patient characteristics for 13 of the included studies are provided in an appendix. Aside from one table for eight of the nine studies listed in section 1.2,‘Literature related to side effects and cosmetic outcome after IORT as a single treatment’, the MS does not provide summary tables for the included studies. There is no quality assessment of the included studies.

l Are their conclusions similar to ours?

¢ In the MS section‘Interpretation of clinical evidence’ subsections a, b, and c, the focus is on the TARGIT-A trial data and, consequently, with only one included trial there is no evidence to draw together and interpret. Therefore, for the outcomes of recurrence and overall survival the MS and the SHTAC’s systematic review that report on the same data as published in the 2014 TARGIT-A trial publication.65

¢ In some of the remaining subsections of the MS‘Interpretation of clinical evidence’, the MS discusses evidence for outcomes that are also included in the SHTAC’s systematic review (e.g. subsection

d: Cosmetic outcome and toxicities, subsection f: Quality of life) drawing not only on evidence from the TARGIT-A trial but also on evidence from included cohort studies that support the data from the TARGIT-A trial. Where the SHTAC’s review reports a small amount of additional information on early complications reported by the initial TARGIT-A trial publication64_{this does not impact on the overall}

conclusions. Other subsections of the MS‘Interpretation of clinical evidence’ draw on cohort or other non-RCT studies to provide information to support other hypotheses that are not included within the SHTAC’s systematic review (e.g. subsection e: Side effects and impacts on critical organs are less in IORT than EBRT, subsection g: IORT can be administered to patients where EBRT is not advised, subsection i: Low risk of inducing secondary cancer).

l Any indirect comparisons and if so, was this appropriate and what were key results?

¢ There is no indirect comparison.

l Any extra adverse event information?

¢ None that meets the inclusion criteria for the SHTAC’s systematic review. Interpretation

l Does their interpretation of the clinical data match their analyses?

¢ As already noted above, with only one included trial there is no evidence to draw together and interpret.

Questions

l Any areas of uncertainty/discrepancy compared with the SHTAC’s review?

¢ None related to the key TARGIT-A trial. Other evidence presented by the MS does not meet the inclusion criteria for the SHTAC’s systematic review.

Southampton Health Technology Assessments Centre’s critique