Discussing surgical innovation with patients: a qualitative study of surgeons’ and governance representatives’ views

Objectives Little is known about how innovative surgical procedures are introduced and discussed with patients. This qualitative study aimed to explore perspectives on information provision and consent prior to innovative surgical procedures. Design Qualitative study involving semi-structured interviews. Interviews were audio recorded, transcribed and analysed thematically. Participants 42 interviews were conducted (26 surgeons and 16 governance representatives). Setting Surgeons and governance representatives recruited from various surgical specialties and National Health Service (NHS) Trusts across England, UK. Results Participants stated that if a procedure was innovative, patients should be provided with additional information extending beyond that given during routine surgical consultations. However, difficulty defining innovation had implications for whether patients were informed about novel components of surgery and how the procedure was introduced (ie, as part of a research study, trust approval or in routine clinical practice). Furthermore, data suggest surgeons found it difficult to establish what information is essential and how much detail is sufficient, and governance surrounding written and verbal information provision differed between NHS Trusts. Generally, surgeons believed patients held a view that ‘new’ was best and reported that managing these expectations could be difficult, particularly if patient views aligned with their own. Conclusions This study highlights the challenges of information provision and obtaining informed consent in the context of innovative surgery, including establishing if and how a procedure is truly innovative, determining the key information to discuss with patients, ensuring information provision is objective and balanced, and managing patient expectations and preferences. This suggests that surgeons may require support and training to discuss novel procedures with patients. Further work should capture consultations where new procedures are discussed with patients and patients’ views of these information exchanges.

BUT, this is exactly the same in the situation of getting informed consent for standard surgery! We do not know with 100% certainty what are the risks and benefits, and outcomes/successes, of ANY surgery. There might be smaller confidence intervals around risks, benefits, and outcomes of standard surgery, but uncertainty and the need to educate patient about it, is still present.
Here is an excerpt from the narrative, which is an example of the type of narrative/comparison that I object to: "There was a consensus both across and within participant groups that if a procedure is deemed to be innovative, patients should be provided with additional information extending beyond that given during routine surgical consultations. The potential risks and benefits, alternative treatment options, and the novel status of the procedure were universally regarded as essential information…" Does this statement mean that the participantsor investigatorsbelieved that individuals getting a "routine" surgical procedure do NOT have to be told about risks and benefits or alternative treatments? I really hope not. But it is instances like this that reduce my enthusiasm for this presentation of this study.
To this reviewer, the current manuscript sets up innovative surgery as something that is qualitatively different from standard surgery. However, this seems to me to be an inappropriate way to think about it. And there is justification for this view even in the narrative itself. For example, one of the included quotes discusses that it is really a continuum.
Thus, to me the counter positioning of standard vs innovative is a mistake and distraction. Instead, I would see all surgeries (and any type of medical intervention actually), as on a continuum of "familiarity" where at one end there are interventions such as cataract surgery (thousands done every year, and quite precise information on the likelihood of success or different side effects). And at the other end are things like the Concorde Lift Expandable Interbody Device. Therefore, the idea of a continuum rather than "Comparison of different types of things" might make more sense.

"Stakeholders"
The results presented here include only information from physicians and "government representative". Because patients or potential patients are not included in this study (or at least the data presented here), there is a gaping hole in the information on the topic of discussions of innovative surgical procedures. Without the patient view, it is much harder to find or describe how this research will contribute to the overall issue of informing patients about innovative surgical procedures.
Therefore, if the overall study did also collection information from patientswho in my mind are the most important "stakeholders" in this situation -I would strongly encourage the investigators to include those data in this manuscript.

Title & Relationship to Informed Consent:
Because the title uses the phrase "Informed consent", I was expecting that the results would in fact say something about informed consent. But instead, although the narrative lightly links the information received from the "stakeholders" to the informed consent process, this is really NOT a study of informed consent as it is so narrowly focused and doesn't yield any specific insights that can help informed consent.

Conclusions in the abstract
As written, the "Conclusion" section of the abstract seems to indicate that there were NO useful findings from the research described here. I would suggest making sure that there are clear statements in the conclusions about what was done and why it is important.

Recruitment and participants
In the methods section on Sampling and recruitment, clarification is needed with respect to the number of potential participants who were invited to take part (n=83, according to the text), vs. the number who were interviewed (n=42). Of the 41 who were invited but did not participate, how many declined and why? How many were "dropped" by the study because saturation had been reached? Laurels

Methods: Data analysis
The processand description of the processfor analyzing the qualitative data was well described and complete. Too many qualitative studies have very weak descriptions of their analyses, or claim that they are using a certain analysis procedure ("grounded analysis" is a huge one), when in fact they are not.

Adaptation of the interview guides/schedules
I applaud the methodology of allowing the interview schedule to develop and be modified based on the information collected (and overall tenor) of the initial interviews.

1)
Since this paper is about informed consent, the authors should state the current legal and ethical requirements for informed consent in the UK at the outset of the paper. 2) There is no clearly stated question or objective to anchor the paper. 3) Methodology has not been addressed and methods require support from the literature. 4) It is not clear how innovations that are introduced via research channels (e.g. clinical trials) fit into this study. Once the authors have had an opportunity to address this feedback, I would gladly review the article again.

Abstract •
The authors state that 26 clinicians participated in this study. If all 26 clinicians were surgeons, please replace "clinician" with "surgeon". Summary of Strengths and Limitations • Bullet #2-Replace "patient" with "patients". Introduction • Para 1, Sentence 2-Provide a citation for the Montgomery ruling.
• Para 1, General Comment-Since the legal standards for informed consent are of great importance in the context of this manuscript, I recommend that the authors use the first paragraph to clearly set out the current legal requirements for informed consent. Specifically, I recommend clearly explaining that the previous standard (the Bolam test) focused on whether the physician had acted in line with responsible body of opinion, whereas the Montgomery ruling set a new standard whereby physicians must ensure that patients are made aware of any material risks (i.e., risks that a reasonable person in the patient's position would find significant). This gives the reader a muchneeded point of reference in terms of what physicians should be doing. • Para 2, Sentence 6-Please revise this sentence for improved accuracy. Suggested wording: "Recognizing these issues, the RESEng has recently published guidelines for the development, implementation and dissemination of surgical innovation, which contains guidance on informed consent". • Para 2, Sentence 7-The listed items do appear in the guidance document that is cited, however, the original citation for these items is a review by Broekman et al. Suggesting wording: "This document suggests, based on findings of a review by Broekman et al citation, that patients should be informed of…..". • Para 3, Sentence 1-The authors state that "…consent in early phase surgical studies or when new or modified surgical treatments are introduced as part of routine clinical practice (e.g., via trust governance processes) has not previously been explored." However, there seems to be a rather substantial body of literature that exploring consent relevant to surgical innovations, as evidenced by the content analysis (Bracken-Roche et al) and other articles (Reitsma and Moreno; Char et al) that are cited by the authors. Please clarify. • Para 3, Sentence 4-The authors refer to a "scarcity of research in this area". What area exactly? There is literature on informed consent in the context of surgical innovation. Is it that the perspectives of stakeholders on how to approach informed consent has not been studied? Please be more explicit with regard to the knowledge gap that is being addressed.
• Para 4, Sentence 1-Similar to the previous comment, the authors write "To address this evidence gap…". Which gap? Please revise paragraph 3 to improve clarity regarding the evidence gap that is being addressed. • Para 4-The specific research objective(s) and/or research question(s) being addressed by this study is unclear. Is the objective to explore how surgical innovations are currently being introduced and discussed with patients in the UK? Please explicitly state. Methods • General Comment-What is the methodology that is being used? The type of qualitative approach, relevant theory/frameworks, and research paradigm have not been addressed.
• General Comment-The methods described are indeed commonly used in qualitative research, however, the methods section is lacking appropriate citations to demonstrate that the approach is based on established practices. The only citation in the entire methods section is for Braun and Clarke, which is a beginner's guide that is geared toward students. This section would be strengthened by the addition of appropriate references (for sampling strategies, use of semi-structured interviews, interview guide design, analytic approach etc.). • Design, Para 1, Sentence 3-Revise to state, "The study is reported in line with the Standards for Reporting Qualitative Research (SRQR) citation." • Sampling and Recruitment, Para 1, Sentence 5-The authors mention that individuals with experience in "first in human procedures" were included in the study. This indicates that the interviews with participants also included conversations about innovations introduced as part of clinical trials. This may have influenced study findings substantially. For example, interventions introduced as part of a clinical trials may be more readily identified by surgeons as "innovative". Moreover, given that consent to participate in research is typically subject to unique regulatory requirements and processes (e.g., REB approval, use specific forms, etc.), it is likely that informed consent requirements in a research-context are more clearly set out compared to a nonresearch context. Please provide information about whether this study encompassed responses pertaining to surgical innovations introduced as research, versus those being introduced solely as clinical care (i.e., no research component), and the implications for study findings.
• Data Collection-The authors have identified two distinct stakeholder groups with whom interviews were conducted: (1) surgeons, and (2) governance representatives. These two groups of individuals would have very different experiences with and perspectives on informed consent in the context of surgical innovation. Please explain why each of these two stakeholder groups were selected and what information you hoped to gain from each groups (e.g., "Governance representatives were included in this study because….").
• Data Collection-The authors explain that the interview guide was developed iteratively. How did the initial interview guide change over the course of the study? • Data Collection-Related to the previous comment, the interview guide that was provided as Appendix 1 seems much more geared toward surgeons. Please provide details about how the questions/focus of the interviews differed between the two groups. How was it adapted for governance representatives?
• Data Analysis-Were transcripts anonymized, or deidentified? If anonymized, please explain process of anonymization. Results • General Comment-Consider reframing the first two themes so that they are not worded as questions.
• General comment -The very first paragraph provides details on study participants, as well as information on data collection. Rather than being placed in the results section, I suggest that this information be placed in the methods section under the appropriate sub-heading (i.e., sampling and recruitment, or data collection data collection).
• "What is Innovation?", fifth quote-The fifth quote under this theme seems to bring up research again (" …if you're not trialling the instrument to see if it's safe…". The quote speaks to recognition that the standards for informed consent differ when the innovation is being introduced as part of clinical trial. The difference in context (research vs. non-research) needs to be addressed by the authors in the manuscript. How do innovations introduced via research channels fit in to this study.
• "What should patients be told?", paragraph 2-The authors identify several types of information (evidence, experience, training, safety precautions, national guidance) as not frequently discussed by physicians, but use quotes that state that experience and evidence are in fact discussed by physicians. I would suggest selecting different quotes to better illustrate the point being made (i.e., quotes illustrating that these things are not frequently discussed). Discussion • Para 2, Sentence 3-Change to "innovative treatments" • Para 5-This is the first time that the authors explicitly address research. The difference in how research is regulated compared to practice changes occurring outside of the scope of research are very different. This should be addressed at the outset of the paper, and warrants substantial attention in the discussion. Re: Standards for reporting qualitative research • Purpose or research question-Not explicitly stated. • Qualitative approach and research paradigm-Not addressed.
• Researcher characteristics and reflexivity-Not addressed. Comments for authors: This manuscript reports results of a qualitative study which collected information from both physicians and government representative on the topic of innovative surgical procedures. Although this topic is an interesting and potentially important topic, and the investigators /manuscript have several laudable facets (noted below), there are also a number of concerns which substantially reduce my enthusiasm for the manuscript as written.
These concerns are described first below, and are somewhat ordered by importance. Laudatory elements of the manuscript follow.

"Innovative surgery" compared to "standard surgery"
Perhaps this is a philosophical or semantic quibble, but I don't think so. I was unhappy with the comparison throughout the manuscript of "innovative" versus "standard" surgery and so how the informed consent process for innovative surgery must be quite different from "standard" surgery. For example, much is made of the fact that there are uncertainties in risks and benefits in innovative surgeryand thus the need for good communication between physicians and patients for good informed consent. BUT, this is exactly the same in the situation of getting informed consent for standard surgery! We do not know with 100% certainty what are the risks and benefits, and outcomes/successes, of ANY surgery. There might be smaller confidence intervals around risks, benefits, and outcomes of standard surgery, but uncertainty and the need to educate patient about it, is still present. Here is an excerpt from the narrative, which is an example of the type of narrative/ comparison that I object to: "There was a consensus both across and within participant groups that if a procedure is deemed to be innovative, patients should be provided with additional information extending beyond that given during routine surgical consultations. The potential risks and benefits, alternative treatment options, and the novel status of the procedure were universally regarded as essential information…" Does this statement mean that the participantsor investigatorsbelieved that individuals getting a "routine" surgical procedure do NOT have to be told about risks and benefits or alternative treatments? I really hope not. But it is instances like this that reduce my enthusiasm for this presentation of this study.
To this reviewer, the current manuscript sets up innovative surgery as something that is qualitatively different from standard surgery. However, this seems to me to be an inappropriate way to think about it. And there is justification for this view even in the narrative itself. For example, one of the included quotes discusses that it is really a continuum. Thus, to me the counter positioning of standard vs innovative is a mistake and distraction. Instead, I would see all surgeries (and any type of medical intervention actually), as on a continuum of "familiarity" where at one end there are interventions such as cataract surgery (thousands done every year, and quite precise information on the likelihood of success or different side effects). And at the other end are things like the Concorde Lift Expandable Interbody Device. Therefore, the idea of a continuum rather than "Comparison of different types of things" might make more sense.

Response:
We thank the reviewer for highlighting these critical points. It is absolutely correct that for standard surgery it is the responsibility of the surgeon to discuss with patients the risks and benefits and the treatment alternatives we were not proposing otherwise. This would be in keeping professional guidance for information provision for informed consent. We also agree with the point made that there is a spectrum and continuum of standard practice through to true innovation. We do think, however, that at the 'innovation end' of this spectrum the process of informed consent and information provision differs to that required for more routine procedures because of the additional 'unknown unknowns'. We have amended the methods section and the discussion to clarify these points and to include the helpful comments from the reviewer.
Changes to the methods section (page 6): As there is no standardised definition for innovation (14,26,27), and because surgical innovation is unlikely to involve a single discrete development and it is often a continuum from standard practice through to true innovation (28, 29), participants were asked to reflect what the term meant to them and describe procedures that they deemed to be innovative.
Changes to the discussion section (page 16):

"Stakeholders"
The results presented here include only information from physicians and "government representative". Because patients or potential patients are not included in this study (or at least the data presented here), there is a gaping hole in the information on the topic of discussions of innovative surgical procedures. Without the patient view, it is much harder to find or describe how this research will contribute to the overall issue of informing patients about innovative surgical procedures. Therefore, if the overall study did also collection information from patientswho in my mind are the most important "stakeholders" in this situation -I would strongly encourage the investigators to include those data in this manuscript.

Response:
We completely agree that exploring patient views are very important. This is part of the next phase of the study and it will inform a separate report.
We have now acknowledged this as a key limitation in the strengths and imitations summary section, as well as the abstract conclusion (pages 2/3/4):

'Further work should capture patients' views on information provision in this context, so that recommendations can be made to improve transparency and communication.'
'Further work should capture consultations where new procedures are discussed with patients and patients' views of these information exchanges.'

Title & Relationship to Informed Consent:
Because the title uses the phrase "Informed consent", I was expecting that the results would in fact say something about informed consent. But instead, although the narrative lightly links the information received from the "stakeholders" to the informed consent process, this is really NOT a study of informed consent as it is so narrowly focused and doesn't yield any specific insights that can help informed consent.

Response:
We agree this should have been clearer and the focus if more on information provision than informed consent (although they are linked). We have now changed the title of the manuscript and updating the discussion to include detail on the relationship between information provision and informed consent: New title of manuscript:

"Discussing surgical innovation with patients: A qualitative study of surgeons' and governance representatives' views"
Changes to the discussion section (pages 16/17). We also updated the introduction on page 5see response to the second reviewer below (page 6 of this document): Prior research has shown patients do not always feel fully informed about the different treatment options available to them(52, 53). It is likely that the added complexity associated with innovative treatments (e.g. unknown unknown risks and benefits, lack of long-term data, limited surgeon experience of the technique) makes discussing treatments options particularly challenging for surgeons. This has an impact on the process of information provision within the context of gaining informed consent to undergo the procedure. As many innovations are undertaken within the context of clinical practice and not research, then the information provision is at the discretion of the surgeon. Study participants recognised the importance of communicating the risks and benefits, treatment alternatives, and novel status of a procedure to patients. However, it was less common for interviewees to identify prior training, experience with undertaking the procedure, and the evidence base supporting the innovation as important components of consent in information provision. These elements of information provision are recognised as key to gain informed consent (2,9). The variation observed in this study suggests there is a lack of clarity in guidance for surgeons on what should be disclosed during the content of informed consent discussions in the context of innovative surgery, meaning that some patients are likely to be better informed than others when making treatment decisions. This is a concern given that information provision within the context of informed consent has been linked to patient satisfaction and rates of litigation following surgery(54-56).
Aligning with previous research, our data suggests surgeons may not disclose their personal experience of performing a procedure to patients and this is important to patients (57). In this study few surgeons identified, or reported discussing, surgical experience and/or training as a component of information provision. While we cannot conclude from the current data, the disclosure of this information could lead to conversations regarding the surgical learning curve such discussions could help emphasise to patients that a procedure is novel and there are potential uncertainties in terms of risks and benefits.

Conclusions in the abstract
As written, the "Conclusion" section of the abstract seems to indicate that there were NO useful findings from the research described here. I would suggest making sure that there are clear statements in the conclusions about what was done and why it is important.
Response: Thank you for pointing this out. We have rewritten the conclusion in the abstract to specifically address the implications on informed consent and information provision (pages 2/3): This study highlights the challenges of information provision and obtaining informed consent in the context of innovative surgery, including establishing if and how a procedure is truly innovative, determining the key information to discuss with patients, ensuring information provision is objective and balanced, and managing patient expectations and preferences. This suggests that surgeons may require support and training to discussing novel procedures with patients. Further work should capture consultations where new procedures are discussed with patients and patients' views of these information exchanges.

Recruitment and participants
In the methods section on Sampling and recruitment, clarification is needed with respect to the number of potential participants who were invited to take part (n=83, according to the text), vs. the number who were interviewed (n=42). Of the 41 who were invited but did not participate, how many declined and why? How many were "dropped" by the study because saturation had been reached?
Response: We apologise that this was unclear. We have now added this information on Page 7 of the methods (page 9): Of the 83 participants that were approached, 42 participants were recruited (those who did not participate were unable to find time for an interview or did not respond to the researcher).

Methods: Data analysis
The processand description of the processfor analyzing the qualitative data was well described and complete. Too many qualitative studies have very weak descriptions of their analyses, or claim that they are using a certain analysis procedure ("grounded analysis" is a huge one), when in fact they are not.
Response: Thank you for this positive feedback.

Adaptation of the interview guides/schedules
I applaud the methodology of allowing the interview schedule to develop and be modified based on the information collected (and overall tenor) of the initial interviews.
Response: Thank you for your encouraging comment.

Reviewer 2: Comments
Thank you for the opportunity to review this manuscript. This paper addresses a topic area that has important clinical, legal, and ethical implications-that of informed consent. The submitted manuscript is promising, but I believe it would be strengthened by a number of revisions. I have provided my feedback below and expect that the majority of recommendations will be relatively easy to incorporate, although some will require substantial revisions. Overall, the main things that I feel need to be addressed are as follows: 1) Since this paper is about informed consent, the authors should state the current legal and ethical requirements for informed consent in the UK at the outset of the paper.
Response: Thank you for making this important point. We have now added an overview of the legal requirements (page 5): Until recently, the Bolam ruling meant that a doctor's duty to inform patients prior to surgery was used to judge on whether they had acted in line with the view of a responsible body of medical opinion (1,2). The 2015 Montgomery ruling(3) redefined the standard of informed consent in the United Kingdom (UK) and represented a shift from a paternalistic model of consent to a more patient-centred approach (4,5) meaning that a patient should be told whatever they want to know, not what the doctor thinks they should be told (6).
2) There is no clearly stated question or objective to anchor the paper.
Response: Thank you for pointing this out. We have now added the following to the introduction (page 6): The current study sought to explore surgeons' and governance representatives' views of information provision and informed consent for the introduction of new invasive procedures in the United Kingdom (UK).
3) Methodology has not been addressed and methods require support from the literature.

Response:
We apologise about not including more detail and feel this is an important point. We have now added the following paragraph to the analysis section on page 8:  (Table 2) showing participants' experiences of governance for new procedures: There was variation in how the procedure had been introduced in participants' hospitals. Within this, surgeons' own experiences included requesting approval from their trust's new procedure committee, conducting the procedure in the context of a research study or deeming that approval was not necessary as the procedure was a variation of an existing one (from either judgement of the surgeon or confirmation from a committee).   Para 2, Sentence 6-Please revise this sentence for improved accuracy. Suggested wording: "Recognizing these issues, the RESEng has recently published guidelines for the development, implementation and dissemination of surgical innovation, which contains guidance on informed consent".
Response: Thank you for your suggestionthis has now been updated in the introduction (page 5).
 Para 2, Sentence 7-The listed items do appear in the guidance document that is cited, however, the original citation for these items is a review by Broekman et al. Suggesting wording: "This document suggests, based on findings of a review by Broekman et al citation, that patients should be informed of…..".

Response:
We agree this is a much clearer way of phrasing this and have updated the text with your suggestion on page 5: This suggests, based on findings of a review by Broekman et al (9), that patients should be informed of the innovative nature of the procedure, surgeons' experience with the procedure and the learning curve, the risk and benefitsincluding unknown or unforeseeable risks or outcomes, the evidence or lack thereof, and alternatives to the innovative procedure.
 Para 3, Sentence 1-The authors state that "…consent in early phase surgical studies or when new or modified surgical treatments are introduced as part of routine clinical practice (e.g., via trust governance processes) has not previously been explored." However, there seems to be a rather substantial body of literature that exploring consent relevant to surgical innovations, as evidenced by the content analysis (  (13).
 Para 3, Sentence 4-The authors refer to a "scarcity of research in this area". What area exactly?
Response: We agree this was too vague. We have now added two paragraphs into the introduction section explaining what previous research did and explained how our research builds on this (pages 5 and 6): (13). (14) (15) (16) (17), none have specifically looked at information provision and informed consent. Moreover, these studies were conducted in Australia and Canada and findings may not be generalisable to other countries and different healthcare systems (18). New invasive procedures may be introduced in the context of formal research studies or via local hospital policies (19). The National Institute for Health and Care

Excellence (NICE) recommends that local NHS organisations have appropriate governance structures in place to review, approve and monitor the introduction of new invasive procedures (20). The current study sought to explore surgeons' and governance representatives' views of information provision and informed consent for the introduction of new invasive procedures in the United Kingdom (UK).
 There is literature on informed consent in the context of surgical innovation. Is it that the perspectives of stakeholders on how to approach informed consent has not been studied? Please be more explicit with regard to the knowledge gap that is being addressed.
We have now also added a sentence in the strength and limitations summary box, which explains how this study is unique (page 4):

This is the first qualitative study to conduct in-depth, semi structured interviews to understand current practice for information provision and informed consent for innovative surgical procedures in the United Kingdom.
 Para 4, Sentence 1-Similar to the previous comment, the authors write "To address this evidence gap…". Which gap? Please revise paragraph 3 to improve clarity regarding the evidence gap that is being addressed.
Response: As previously described, we have rewritten the introduction so that it is clearer how the study builds on previous research (page 5 and 6): (13).

Whilst a handful of qualitative studies have been conducted exploring how innovative procedures have been introduced (14) (15) (16) (17), none have specifically looked at information provision and informed consent. Moreover, these studies were conducted in Australia and Canada and findings may not be generalisable to other countries and different healthcare systems(18). New invasive procedures may be introduced in the context of formal research studies or via local hospital policies (19). The National Institute for Health and Care Excellence (NICE) recommends that local NHS organisations have appropriate governance structures in place to review, approve and monitor the introduction of new invasive procedures (20). The current study sought to explore surgeons' and governance representatives' views of information provision and informed consent for the introduction of new invasive procedures in the United Kingdom (UK).
 Para 4-The specific research objective(s) and/or research question(s) being addressed by this study is unclear. Is the objective to explore how surgical innovations are currently being introduced and discussed with patients in the UK? Please explicitly state.
Response: Thank you for highlighting this, we have now added a specific objective to the introduction section as also explained above (page 6):

Methods
 General Comment-What is the methodology that is being used? The type of qualitative approach, relevant theory/frameworks, and research paradigm have not been addressed.

Response:
We have now added the following paragraphs to the methods section (pages 6 and 8): Interviews were considered to be the most appropriate method for this study because they provided the opportunity to encourage participants to think carefully about their own experiences (21), enable the interviewer to respond and follow up on issues raised by the interviewee (22), and that some participants may feel intimidated at the prospect of discussing their experiences within a focus group setting(23).

Thematic analysis was undertaken using the constant comparison technique of grounded theory (41, 42), which involved using the inductive identification of codes from the data to generate new hypotheses about phenomena that are derived or grounded in the data (43). Its central principle is of constant comparison, where new findings are systematically compared with existing data so that similarities and differences can be identified and emerging theories refined through the ongoing assimilation of data (41, 44).
 General Comment-The methods described are indeed commonly used in qualitative research, however, the methods section is lacking appropriate citations to demonstrate that the approach is based on established practices. The only citation in the entire methods section is for Braun and Clarke, which is a beginner's guide that is geared toward students. This section would be strengthened by the addition of appropriate references (for sampling strategies, use of semi-structured interviews, interview guide design, analytic approach etc.).

Response:
Thank you for pointing this out, we completely agree that this will strengthen the methods section considerably. We have added the following information about the methods (pages 6-9): Interviews were considered to be the most appropriate methodology for this study because they provided the opportunity to encourage participants to think carefully about their own experiences [1], enable the interviewer to respond and follow up on issues raised by the interviewee [2], and that some participants may feel intimidated at the prospect of discussing their experiences within a focus group setting [3].
Study recruitment ceased when the qualitative team agreed that theoretical saturation had been achieved (where no new themes were forthcoming from three consecutive interviews) [4,5].
The interviewer began the discussion with more general questions to build rapport [6] such as the participants' background and general views of defining innovation. The interviewee's comments were restated and incorporated into further questions to check with the interviewer that they had understood correctly [7]. In order to gain more detailed and comprehensive understanding of the descriptions given by participants, they were asked to elaborate their comments with explanations and examples (such as, 'Why do you feel this was?') [7], or fillers (such as 'mmm' or 'yeah') were used by the interviewer to show the participant this was something they were interested in and to encourage them to continue [8]. Towards the end of the interview, participants were given an opportunity to raise issues that were important to them that had not already been covered [6].
Thematic analysis was undertaken using the constant comparison technique of grounded theory [9,10], which involved using the inductive identification of codes from the data to generate new hypotheses about phenomena that are derived or grounded in the data [11]. Its central principle is of constant comparison, where new findings are systematically compared with existing data so that similarities and differences can be identified and emerging theories refined through the ongoing assimilation of data [9,12]. Interview recordings were transcribed and anonymised before being imported into a data management program (NVivo version 11) to organise the data systematically, allow for quick searching and refining of codes and categories, increase the transparency of the analysis process and enable team comparisons of coding [4,13]. First, analysts (JZ, DE & SP) read and re-read transcripts before independently coding a sample of five transcripts to begin familiarising themselves with the data [4,14]. Interesting features were coded, whereby a segment of data was assigned a label [15], and on-going potential ideas and coding schemes were noted at every stage of analysis [16]. Codes were compared to ensure some consistency and ensure rigour in the findings [17], whereby differences were discussed thoroughly until a consensus was met and an initial coding frame was developed We have also added the references throughout the methods section so that the following references are included:  Sampling and Recruitment, Para 1, Sentence 5-The authors mention that individuals with experience in "first in human procedures" were included in the study. This indicates that the interviews with participants also included conversations about innovations introduced as part of clinical trials. This may have influenced study findings substantially. For example, interventions introduced as part of a clinical trials may be more readily identified by surgeons as "innovative". Moreover, given that consent to participate in research is typically subject to unique regulatory requirements and processes (e.g., REB approval, use specific forms, etc.), it is likely that informed consent requirements in a research-context are more clearly set out compared to a non-research context. Please provide information about whether this study encompassed responses pertaining to surgical innovations introduced as research, versus those being introduced solely as clinical care (i.e., no research component), and the implications for study findings.
Response: Thank you for pointing this out. As previously mentioned, we have now added the following to the results section on page 9: There was variation in how the procedure had been introduced in participants' hospitals. Within this, surgeons' own experiences included requesting approval from their trust's new procedure committee, conducting the procedure in the context of a research study or deeming that approval was not necessary as the procedure was a variation of an existing one (from either judgement of the surgeon or confirmation from a committee).   Data Collection-The authors have identified two distinct stakeholder groups with whom interviews were conducted: (1) surgeons, and (2) governance representatives. These two groups of individuals would have very different experiences with and perspectives on informed consent in the context of surgical innovation. Please explain why each of these two stakeholder groups were selected and what information you hoped to gain from each groups (e.g., "Governance representatives were included in this study because….").

Response:
We have now added the following information to the introduction and methods on page 6: New invasive procedures may be introduced in the context of formal research studies or via local hospital policies (19). The National Institute for Health and Care Excellence (NICE) recommends that local NHS organisations have appropriate governance structures in place to review, approve and monitor the introduction of new invasive procedures (20).
Governance representatives (defined as those involved in regulating the introduction of new/modified procedures and/or devices at trust or national levels) were included to understand what processes were in place for the introduction of new procedures (17). Surgeons were recruited to explore experiences of introducing new/modified procedures or devices into clinical practice.
 Data Collection-The authors explain that the interview guide was developed iteratively. How did the initial interview guide change over the course of the study?

Response:
We have now provided the following information about the topic guides in the section on data collection on page 7 and 8: Separate topic guides were developed for governance representatives and surgeons. All interview schedules contained core topics of interest (e.g. 'How would you define innovation?', 'What does informed consent mean to you?') [18,19], although these were flexible to allow participants to shape the direction of conversations [7,20]. Governance representatives were asked how applications were processed and how these procedures are integrated into practice, whereas surgeons were about their experiences of introducing a procedures and what patients had been told. An example of an interview schedule is provided in the supplementary files (Additional files 2 and 3).

Topic guides were developed iteratively during the study period, in consideration of emerging insights from interviews and better ways of phrasing questions(29, 35). For instance, interviewers (non-clinical academics) used more prompts to encourage the surgeons to describe procedures in a non-technical manner (31). Topic guides were initially very long so
were reduced to include more 'mapping' questions that addressed the core components of interest (such as, 'I understand you've conceptualised a new procedure. Can you talk me through this?'). Additional prompts were added from emerging findings (i.e. colleagues' reactions to procedures and written information).
 Data Collection-Related to the previous comment, the interview guide that was provided as Appendix 1 seems much more geared toward surgeons. Please provide details about how the questions/focus of the interviews differed between the two groups. How was it adapted for governance representatives?

Response: We have now included examples in the Supplementary files.
 Data Analysis-Were transcripts anonymized, or de-identified? If anonymized, please explain process of anonymization.

Response:
We have now clarified that transcripts were de-identified on page 8: Interview recordings were transcribed and de-identified so that names and identifiable information were removed.

Results
 General Comment-Consider reframing the first two themes so that they are not worded as questions.

Response:
We have rephrased the theme names, as summarised on page 9:

Findings related to informed consent are presented under four main themes: difficulty defining innovation, differing views on whatand how -patients should be told, the challenges of discussing uncertainty, and managing patient expectations.
 General comment -The very first paragraph provides details on study participants, as well as information on data collection. Rather than being placed in the results section, I suggest that this information be placed in the methods section under the appropriate sub-heading (i.e., sampling and recruitment, or data collection data collection).
Response: Thank you for spotting thiswe have now moved this information into the sampling and recruitment section in the methods on page 9:  "What is Innovation?", fifth quote-The fifth quote under this theme seems to bring up research again (" …if you're not trialling the instrument to see if it's safe…". The quote speaks to recognition that the standards for informed consent differ when the innovation is being introduced as part of clinical trial. The difference in context (research vs. non-research) needs to be addressed by the authors in the manuscript. How do innovations introduced via research channels fit in to this study.
Response: As mentioned, we have now added a section in the results about the difference contexts that innovative procedures can be introduced (see pages 7 and 8 of this document).
 "What should patients be told?", paragraph 2-The authors identify several types of information (evidence, experience, training, safety precautions, national guidance) as not frequently discussed by physicians, but use quotes that state that experience and evidence are in fact discussed by physicians. I would suggest selecting different quotes to better illustrate the point being made (i.e., quotes illustrating that these things are not frequently discussed).
Response: Thank you for bringing this to our attention. We have now rephrased this on page 12, and added different quotes:

Discussion
 Para 2, Sentence 3-Change to "innovative treatments" Response: This has been updated on page 16 (now paragraph 3, sentence 2)-thank you for noticing this: It is likely that the added complexity associated with innovative treatments  Para 5-This is the first time that the authors explicitly address research. The difference in how research is regulated compared to practice changes occurring outside of the scope of research are very different. This should be addressed at the outset of the paper, and warrants substantial attention in the discussion.

Response:
We have now added the following information to the introduction (page 5): New invasive procedures may be introduced in the context of formal research studies or via local hospital policies (16). The National Institute for Health and Care Excellence (NICE) recommends that local NHS organisations have appropriate governance structures in place to review, approve and monitor the introduction of new invasive procedures (17).
On pages 11 and 12 we have also added a section to the results section if surgeons obtained approval to perform the procedure, and whether this was as part of a research study or approved by a hospital committee (see pages 7 and 8 of this document). We have also now reflected upon this in the discussion on page 15:

Response:
We have now clarified the objectives of the research on page 5: The current study sought to explore stakeholder views of information provision for the introduction of new invasive procedures in the United Kingdom (UK).
 Qualitative approach and research paradigm-Not addressed.
Response: More information has been added on page 7 of the methods section:

GENERAL COMMENTS
Thank you for the opportunity to review this revised manuscript. I commend the authors for their careful consideration of reviewer comments and the great deal of effort that was clearly put into revising this manuscript. It is my opinion that the manuscript has been much improved and more effectively communicates the work that was carried out. In particular, I think the revisions to the introduction and methods sections were very well done. After reading through the revised manuscript, I do have additional comments, which are listed below (most are editorial in nature).
Specific comments: Title page-The title has changed. Does the running head need to change as well? Introduction-The authors have done a great job of explaining the current body of literature and identifying knowledge gaps. Introduction, paragraph 1, sentence 2-Change "a doctor's duty to inform patients prior to surgery was used to judge on whether they had acted in line with the view of a responsible body of medical opinion" to "a doctor's duty to inform patients prior to surgery was judged based on whether they had acted in line with the view of a responsible body of medical opinion." Introduction, paragraph 2, sentence 4-Change "patients-clinician" to "patient-clinician".  Table 2 highlights that how the…" with " Table 2 highlights that the." Results, Analysis, Difficulty defining innovation-The table regarding governance (which I think is helpful) is followed by a quote ("So, I'm not convinced that every innovative thing in the trust goes through the committee…). In looking at the markup version, I believe this may have been included in error. Results, Analysis, Differing views on what-and how-patients should be told, paragraph 2-Replace "such be disclosed" with "should be disclosed". Results, Analysis, The challenges of discussing uncertainty-I realize the title of this theme has already been changed once, but I am still not sure that the current title accurately reflects the description of the theme. To be, theme seems to be about the challenges of discussion innovations with patients, not so much the challenges of discussing uncertainty (which comprises only a small portion of the description of the theme). Results, Analysis, Managing patient expectations-Regarding the sentence "Managing patients' preferences, particularly if they align with the personal preferences, appeared challenging for some", should this be "particularly if they align with the personal preferences of the surgeon"? Discussion, paragraph 2, sentence 6-Replace "This meant that patient information provided…" with "This meant that information provided to patients…". The title of Additional File 2 is "Topic guide for interviews with data committee members". Consider changing to "Topic guide for interviews with governance representatives". The title of Additional File 3 is "Topic guide for interviews stakeholders". Consider changing to "Topic guide for interviews with surgeons".

Reviewer: 1
The authors of this manuscript have done a very detailed and comprehensive revision based on the reviews that they received. They have satisfactorily addressed all of my concerns and (I believe, although up to the other reviewer) the concerns of the other reviewer as well.
Response: Thank you for the positive feedback. We were grateful for your comments and felt they very much strengthened the manuscript.

Reviewer 2
Thank you for the opportunity to review this revised manuscript. I commend the authors for their careful consideration of reviewer comments and the great deal of effort that was clearly put into revising this manuscript. It is my opinion that the manuscript has been much improved and more effectively communicates the work that was carried out. In particular, I think the revisions to the introduction and methods sections were very well done. After reading through the revised manuscript, I do have additional comments, which are listed below (most are editorial in nature).

Specific comments:
Title page-The title has changed. Does the running head need to change as well?
Response: This has been updated (page 16).
The title of Additional File 2 is "Topic guide for interviews with data committee members". Consider changing to "Topic guide for interviews with governance representatives".

Response:
The title has now been updated.
The title of Additional File 3 is "Topic guide for interviews stakeholders". Consider changing to "Topic guide for interviews with surgeons".

Response:
The title has now been updated.

VERSION 3 -REVIEW REVIEWER
Cynthia Kendell Nova Scotia Health Authority, Canada REVIEW RETURNED 15-Jun-2020

GENERAL COMMENTS
Thank you for inviting me to review these additional revisions. I have read through the manuscript, and again appreciate the effort that has gone into these changes. Several additional changes are required to the most recently uploaded version of the manuscript, which is due in part to the fact that one of my comments was not well communicated. My apologies for not being clear. I have attempted to provide clarification in my comments below.

Methods •
The authors stated in their response that the ethics statement could now be found under "Methods", but it does not seem to appear anywhere in the manuscript (likely just a copy and paste error). Please ensure this statement is included.

Methods, Design •
My previous comment about this section was not clear. In order to be clearer, I have provided an example of how this section may be structured and worded. Please be sure to include an appropriate citation for grounded theory. "This qualitative study employed a grounded theory methodology [citation]. Grounded theory methodology was chosen because/is appropriate because____________. Consistent with grounded theory methodology, semi-structured interviews were conducted with relevant stakeholders." • Currently the following text appears under Design: Governance representatives (defined as those involved in regulating the introduction of new/modified procedures and/or devices at trust or national levels) were included to understand what processes were in place for the introduction of new procedures 17. Surgeons were recruited to explore experiences of introducing new/modified procedures or devices into clinical practice. As there is no standardised definition for innovation and it is often a continuum from standard practice through to true innovation 14 21 22, and because surgical innovation is unlikely to involve a single discrete development 23 24, participants were asked to reflect what the term meant to them and describe procedures that they deemed to be innovative. This information feels out of place under Design. I suggest moving this text back to where it was previously found, under Participants and Recruitment. Methods, Data Collection

•
The authors have included the following passage under Data Collection: Interviews were considered to be the most appropriate method for this study because they provided the opportunity to encourage participants to think carefully about their own experiences 36, enable the interviewer to respond and follow up on issues raised by the interviewee 37, and that some participants may feel intimidated at the prospect of discussing their experiences within a focus group setting27 I have two comments about this passage of text. First, I suggest moving it to the very beginning of the Data Collection subsection. As such, the first several paragraphs under Data Collection would appear in the following order: 1) "Interviews were considered to be the most appropriate…" 2) "All participants received…" 3) "The interviewer began the discussion…" My second comment is that I suggest removing "and that some participants may feel intimidated at the prospect of discussing their experiences within a focus group setting27" and adding the following sentence in its place " Interviews were chosen instead of focus groups as it was felt that some individuals may feel intimidated at the prospect of discussing their experiences within a focus group setting."

VERSION 3 -AUTHOR RESPONSE
Reviewer's comments: Thank you for inviting me to review these additional revisions. I have read through the manuscript, and again appreciate the effort that has gone into these changes. Several additional changes are required to the most recently uploaded version of the manuscript, which is due in part to the fact that one of my comments was not well communicated. My apologies for not being clear. I have attempted to provide clarification in my comments below.

Response:
We are very pleased to see that the changes to the paper were well-received and we appreciate the reviewer's helpful and constructive comments. We have listed our response to each point raised by the reviewer and highlight the changes made to the manuscript. We look forward to your response.

Methods
The authors stated in their response that the ethics statement could now be found under "Methods", but it does not seem to appear anywhere in the manuscript (likely just a copy and paste error). Please ensure this statement is included.

Methods, Design
My previous comment about this section was not clear. In order to be clearer, I have provided an example of how this section may be structured and worded. Please be sure to include an appropriate citation for grounded theory.
"This qualitative study employed a grounded theory methodology [citation]. Grounded theory methodology was chosen because/is appropriate because____________. Consistent with grounded theory methodology, semi-structured interviews were conducted with relevant stakeholders."

REVIEWER
Cynthia Kendell Nova Scotia Health Authority, Canada REVIEW RETURNED 03-Sep-2020

GENERAL COMMENTS
Thank you to the authors for your careful consideration of the feedback provided throughout the review process. All of my comments have been satisfactorily addressed in the most recent version of the manuscript. I have no additional comments.