Pharmaceutical industry, academia and people with experience of mental illness as partners in research: a need for ethical guidance [version 1; peer review: 1 not approved]

Background: Several social and policy developments have led to research partnerships in mental health research, which depart from traditional research models. One form of such partnerships is among research institutions, industry (pharmaceutical and biotech) and people with lived experience of mental illness (RIPs). There are several benefits but also ethical challenges in RIPs. An ethics-based approach to anticipating and addressing such ethical issues in mental health research is lacking. Given the expansion of RIPs in treatment development for mental health illness, guidance to support ethical and trustworthy collaborative mental health research projects is essential. Methods: To develop a moral framework for evaluating the ethics of RIPs, we systematically searched PubMed for peer-reviewed literature discussing good practices in research partnerships. Searches were also conducted in websites of known organizations supporting patient engagement with industry in mental health research and in the references of short-listed articles. Following application of exclusion criteria, remaining articles were critically examined and summarised to synthesise principles for ethically acceptable RIPs and inform clear guidance and practices. Results: Critical analysis and synthesis of the short-listed articles highlighted the need for two sets of principles to guide ethical RIPs: principles for (a) RIPs as a trustworthy enterprise (e.g. public accountability, transparency) and (b) fair RIPs (e.g. effective governance, respect). We discuss the application of these principles in problem-solving strategies that can support best practice in establishing fair and successful mental health research partnerships among research institutions, industry and people with lived experience of mental illness. Conclusions: Ethical guidance is needed to prevent and address challenges in RIPs and to promote the scientific and social benefits of these new research partnership models in mental health research. We Open Peer Review


Introduction: Industry, academia and people with experience of mental illness as partners in research and the rise of new ethical challenges
Several social and policy developments have led to research partnerships in mental health research which depart from traditional research models. One form of such research partnerships is among research institutions, industry (pharmaceutical and biotech) and people with lived experience of mental health challenges (RIPs). There are different types of RIP partnerships (e.g. EU Innovative Medicines Initiative; UK Clinical Research Collaboration; Clinical Trials Transformation Initiative) and various kinds of collaboration strategies i . RIPs are promoted by government, industry and academia as advantageous due to their potential for scientific progress and benefits to society (https://www.nihr.ac.uk/blog/its-simple-mental-health-researchcollaboration-will-improve-lives/11036). Yet, despite current enthusiasm about their value, RIPs present new challenges to mental health research, which could affect the potential of long-term collaborations and the research itself. These challenges include: the aim to combine competing interests and priorities of diverse research partners; the existence of systemic power imbalances among mental health stakeholders; and a lack of transparency in the structure of roles and mutual obligations of the three partnering entities 1 .
Progress is being made in developing ethical guidance for research partnerships in mental health research in two areas: managing conflicts of interest in academia-industry partnerships 2 ; identifying ethical and practical challenges presented in PPI in research 3 . However, an ethics-based approach to anticipating and addressing ethical issues that arise when academia, industry and PPI stakeholders are partnering in mental health research is lacking. Existing guidance documents directed at the pharmaceutical industry, patient groups, clinicians/researchers and other stakeholders (e.g. Consensus Framework for Ethical Collaboration 4 ; EUPATI Ethical Framework 5 ) aim to provide ethical guidance for health research in general and thus do not grasp the complexities of RIPs in mental health research.
Given the expansion of RIPs in the development of treatments for mental health illness, it is important that practical and ethical guidance is provided on potential conflicts and barriers to research when these partnerships are formed. It is also important that such guidance not only recognises the intrinsic social purpose of conducting research but also takes into account the wider social and political context in which such partnerships are formed. Here we propose a moral framework to guide research partners in designing, sustaining and assessing an ethical and trustworthy collaborative mental health research project. We then briefly discuss problem solving strategies to stimulate future research in this area.

Methods
To acquire a comprehensive overview of ethical principles that should guide research partnerships among industry, academia and psychiatric users, we first conducted a scoping literature review.

Eligibility criteria and information sources
To be included in the review, papers needed to focus on ethical principles or practices for partnerships in health research. To identify potentially relevant documents, the MEDLINE database was searched for peer-reviewed literature from January 2015 to May 2020. The search strategy was developed and conducted twice by the authors (the second time for validation) and can be found in Table 1. The search was conducted in PubMed. Peer-reviewed journal papers were included only if they were written in English.
The electronic database was supplemented by scanning websites of known organizations supporting patient engagement with industry in mental health research (e.g. the United Kingdom's National Institute for Health Research (NIHR) the European Patients Academy (EUPATI)) and international standards guidelines and ethics codes, such as the World Medical Association's Declaration of Helsinki, the European Federation of Pharmaceutical Industries and Associations (EFPIA), and others. Finally, the reference lists of these sources were examined to identify any additional publications. No filters regarding country of origin were used.

Selection of sources, data charting and synthesis
We evaluated the titles and abstracts of all publications for potential relevance. A data-charting form was used by the authors to determine the criteria for inclusion. Sources were classified based on the types of entities in collaboration and the associated proposed best practices. Articles and codes of practice were excluded if they (a) were not related to ethics (b) were focusing only on resource-limited settings or (c) did not concern partnerships/networks/collaborations with at least two of the three entities in RIPs. The remaining sources were full-texted assessed for eligibility by excluding those that did not describe specifically best practices in research partnerships/networks/collaborations with at least two of the three entities in RIPs. Finally, the proposed principles and strategies in the resulting set of sources were critically examined, summarised and synthesised. For a visual representation of the search strategy and the results, please see the flow diagram in Figure 1.

Selection of sources
The PubMed search resulted in 279 papers. 12 extra records were identified through manual scan of reference lists of key papers and 7 extra records were identified through manual scan of websites of established organisations. Evaluation of paper titles and abstracts resulted in 74 shortlisted papers. These either (a) described the ethics of patient stakeholder engagement/involvement in industry-sponsored clinical research or medicines research and development or (b) described the ethics of academia-industry partnerships or (c) discussed i In the IMI model, public-private partnership between the European Union and the European pharmaceutical industry is well valued while PPI is strongly encouraged; In the NIHR services PPI is a requirement at the very start of academic research but with a less clear role in industry-sponsored studies.

Synthesis of individual sources
We reviewed the contents of all 37 included articles/reports to determine their usefulness for creating the principles of ethically acceptable RIPs. We then quantified the number of times each foundational principle and best practice was reported. Yet, we identified several important limitations with this approach: A) Not all reported principles guiding research partnerships between two of the three partnering entities of RIPs might be applicable or appropriate to guide ethical RIPs ii . B) The fact that an ethical principle or value is not frequently reported does not imply that it is less relevant or important for RIPs.
To address these problems, we drew on the principles of hermeneutic review 6 to critically examine, summarise and synthesise existing principles and strategies for ethically acceptable RIPs. We thematically grouped the foundational principles and best practices identified from the scoping review based on how they captured the unique features and challenges presented in RIPs. This approach enabled us to both identify weaknesses in the dominant ethical approaches for addressing the complexity of RIPs and to develop a theoretically informed framework based on a range of resources and adapted to be useful in practice. We ended up with two distinct but inter-related set of principles that should guide ethical RIPs in mental health research: 'Ethical principles that should guide trustworthy RIPs' and 'Ethical principles that should guide fair and effective RIPs'.
In the following paragraphs we present the results of this analysis and propose a framework for ethically evaluating RIPs in mental health research. We have two objectives: one is to enhance clarity about the ethical acceptability of RIPs; the second is to help RIP partners in taking actual steps to ensure that best practices are followed when planning and forming such partnerships and conducting research.
A moral framework for evaluating the ethics of RIPs RIPs as a trustworthy research enterprise. Academic researchers, pharmaceutical companies and lay partners have interests (e.g. scientific recognition, financial gain, political agenda) that can conflict with the primary goal and the ethical conduct of health research. Conflicts of interests, if not effectively managed, may introduce unreliability into the research process and undermine the social value of the study and public trust. These problems are intensely prevalent in mental health research 7 and add further complications in RIPs. In particular, challenges regarding patient representation and diversity raise important issues of impartiality and accountability for RIPs at both partnership and public level. Recent studies suggest that researchers may favour PPI groups that are likely to share their views and legitimise their scientific endeavours 8 . Additionally, concerns are often expressed of industry's undue influence on other partners and the ways by which pharmaceutical companies can mask their role in selecting and even managing mental health projects (e.g. by discouraging contrary viewpoints, offering incentives, and delaying the release of research results 9 ). Recent accusations against some patient groups for failure to reveal the scale of drug company investment [10][11][12][13] and for encouraging therapies with problematic clinical profiles and cost effectiveness 14 add further concerns for the ethical credibility of RIPs in mental health research. Given, the ethically problematic history of relations between the profession of psychiatry and psychiatric 'users' and the accusations of unethical practices regarding the role of industry in this already fragile enterprise (e.g. data fabrication, violation of academic freedom, suppression of negative results, etc), clarity and guidance is important for the ethical acceptability of RIPs.
For RIPs to have the same legitimacy and credibility as traditional models in mental health research, the following ethical criteria iii must be fulfilled:

Scientific integrity
For a mental health study to be ethically justified it must have scientific and social value. A necessary condition then for RIPs to be trustworthy is to ensure that their studies are scientifically sound (e.g. follow the core scientific principles of objectivity, transparency, and quality assurance) and likely to generate valuable information 4,15-17 . RIPs must avoid scientific misconduct (data falsification, plagiarism, etc.), address any methodology or bias concerns and ensure that highest standards are followed when their studies are designed, conducted, and reported.

Commitment to research ethics principles
Research partnerships can constitute mutual beneficial collaborations but to be ethically acceptable the potential for each partner to pursue their own interests needs to be constrained by the ethical imperatives of research ethics. This means that the ethical acceptability of RIPs rests on a shared commitment to maximise the potential benefit to society by the production of new knowledge while abstaining from any mistreatment or injustice to research participants and their communities (e.g. studies resulting in serious harms for participants must be terminated despite financial consequences or professional or personal disappointments) 4,5, 15 . For RIPs to be ethically credible all partners should jointly comply with relevant legal and ethical requirements for the conduct of mental health research as they apply in each case (biomedical research, psychological ii for instance, 'equality' may be a fundamental ethical principle for certain partnership models between psychiatric users and academic researchers but lead to exploitation in partnership models where responsibilities among partners cannot/should not be equally distributed.
iii The aim of this paper is not to respond to concerns about the value of patient involvement in research or whether industry-academia partnerships can be ethically attenable. As both these positions may be controversial, we presume that if RIPs follow a set of acceptable ethical standards, they are ethically justifiable.
research, etc) 14,18 . RIPs should ensure that all partners involved are appropriately educated and trained to fulfil their ethical responsibilities according to their role 16 .

Professional autonomy and independence
For RIPs to be a trustworthy and ethical research enterprise, all partners should demonstrate common commitment to professional integrity and autonomy. Partners interactions, arrangements and relationships should be appropriate over all stages of research 4,5, 9,17 . When academic researchers are engaging with funders and patient groups they should adhere to the ethical codes of their own organisation and the existing legislations (e.g. not compromise their academic freedom, independent inquiry, the right to publish etc) 4, 14,15 . Pharmaceutical industry should operate according to their rights (or lack thereof) as a partner with regard to all aspects of research (e.g. ownership and access to research data) 18 . The independence of patients/patient organizations and other provisions set out in existing codes of conduct should be respected by all partners 19 . No financial or other benefits should be sought, provided or accepted that may compromise their ethical obligations to their research participants and society.

Transparency
Transparency is important to restore public's trust in science and research collaborations in mental health as it helps partners to identify (and potentially address) ethical issues that could undermine the trustworthiness of research. RIPs should establish clear disclosure processes (e.g. formal written conflict of interest management plans), so that partners' (present and past) commitments and affiliations with other parties or companies, their political and financial interests and the partnership's objective, scope and policies are visible and known to the public 4,9,20,21 .

Public accountability
To maintain public trust RIPs have ethical obligation to ensure public accountability of research and its results. RIPs should ensure that all research partners adhere to the underlying principles for the potential social benefits of research, prospectively register their studies 14 , comply with recognised publication ethics guidelines, and disclose both positive and negative results 14 . RIPs should also develop transparent and clear communication strategies for the public to be aware about their aims, policies and the results of their work and promote public discussion 4, 9,17 .

RIPs as an effective and fair research enterprise.
Competing interests and priorities among partners may cause internal ethical problems in RIPs and present barriers to the conduct of research. Disagreements may arise in setting research agendas, research methodologies, recruitment strategies, the analysis or communication of research 22-25 . Disagreements may also arise because of partners' different expectations about their roles and contribution or about how partnership should work in practice. Such conflicts are common in research partnerships and subject to negotiation 26 . However, managing tensions in RIPs may be challenging for both ethical and practical reasons. First, due to substantial heterogeneity within both mental health researcher communities and patient/carers communities, tensions arising from differing perspectives may occur among partners and within each partner group. In these cases, weighting diverse interests and views cannot be a straightforward process. Second, in RIP models, the third partner is not explicitly in relationship with the other two primary partners iv . Lack of transparency regarding RIP structures may further complicate transparent articulation of processes to address irreconcilable differences. Third, systemic power and control inequalities imbedded in the mental health context may affect partnership dynamics and partners negotiations (i.e. the extent to which they will be involved in decisions and research processes). According to evidence, negotiations among unequal partners often result in unfair practices regarding authorship, ownership, and remuneration in research collaborations 21,23 . To ensure that internal problems in RIPs do not cause barriers to knowledge production, consume resources or exacerbate existing inequalities among mental health stakeholders, partners should rely on concrete ethical principles and follow fair practices.
In the following paragraphs we suggest ethical principles that would support successful partnerships, worthwhile health projects 27 and promote fair and ethical relationships among partners in mental health research; these are principles that should guide RIPs at the organisational level.

Respect
For the contribution of all partners to be acknowledged, all research partners (irrespectively of their role or the degree of their involvement) should be considered as valued members of the project and treat each other with respect. RIP members should avoid any act that may cause physical, social or sociological harm to those involved in the project 4,5 and ensure that the rights and reputation of their partners are respected by adhering to highest possible ethical standards 9,17 .

Fairness
To avoid exploitative practices, RIPs should rely on policies and processes that can be shared by all partners involved. RIPs must ensure that their policies recognise the capacities and commitments of all partners, acknowledge everyone's contribution and achievements (e.g. in research publications) and provide compensation when appropriate (e.g. to cover costs for researchers and lay partners training) 5,19 . Commitment to fairness also suggests that research partners must consider the moral responsibilities that each of them has in promoting fair partnerships in the studies they are involved in and the commitments they need to make such partnerships work. For instance, a useful and structured training for research partners on how to iv In the NIHR model for example, the relationship of lay partners with industry and academic researchers is not clear and thus not specified whether patient priorities should be integrated in industry-sponsored research conducted within the NHS. This however is a requirement in all other kinds of NIHR-supported studies.
address conflicts or improve communication could be considered a necessary condition to meaningful working relations rather than a costly and time-consuming practice for those involved 28,29 .
Effective governance Effective governance suggests that RIPs are structured in a way that would facilitate productive research by developing clear management plans regarding roles and responsibilities of each partner (degree and stages of their involvement), expectations of reciprocal benefit and risk sharing. RIPs should also ensure that suitable mechanisms and clear processes exist to foster effective communication among partners 4,25 and fair decision-making processes to control potential conflicts and competing commitments of partners 19,30 and to address problems arising at the beginning and throughout the course of research projects 17 .

Transparency and accountability within RIPs
RIPs should rely on clear, transparent procedures that ensure mutual understanding and promote fairness. Although openness and disclosure are not a panacea 31 for addressing all disagreements and conflicts of interests in research partnerships, they allow research partners to evaluate such conflicts, to determine their likely impact 19,32 and to consider possible solutions. Transparency within RIPs is also important to hold partners accountable to each other in their collaborative activities and ensure that their interactions with each other do not compromise their professional integrity or their obligations towards their research participants and society 5, 9,17 .

Summary
The critical analysis and synthesis of the 37 included articles highlights the need for two sets of principles that should guide ethical RIPs: (a) Principles for RIPs as a trustworthy enterprise (e.g. public accountability, transparency) (b) Principles for RIPs as a fair and effective enterprise (e.g. effective governance, respect).

Discussion: Developing strategies for ethical RIPs in mental health research
To establish ethical and productive RIPs, it is important that the ethical principles discussed above inform clear guidance and practices. To ensure that RIPs are publicly committed to rigorous standards of practice, systems which could prevent and address risks that might undermine meaningful research need to be developed without however putting unnecessary burdens to productive and meaningful partnerships. Below we propose strategies that focus on minimising potential or actual conflicts; and we provide actions that can support best practice in establishing fair and successful mental health research partnerships.

RIPs as a trustworthy enterprise
Updating existing guidelines. For RIPs to have the same credibility and legitimacy as traditional models in mental health research, existing research ethics guidelines need to be tailored appropriately. We recommend updating conflict of interest policies to take into account partners' political, social and commercial interests, prior and existing commitments and affiliations with other organisations and/or businesses. Such disclosure is an important means of minimising risk of bias and undue influence in the conduct and report of research. Existing guidelines should also describe what an appropriate form of accountability may be for different RIP models and types of research.
Enhancing ethics reviews. Current institutional oversight paradigms based on traditional research partnership models do not accommodate RIPs, are thus insufficient to address the unique ethical challenges they present in their research (e.g. conflicts regarding data sharing and intellectual property). As partnership models evolve in mental health research, ethics committees' standard operating procedures should be adapted to ensure that all elements of the framework set out in this paper are adequately addressed. In certain cases (e.g. high-risk studies) monitoring systems may also be appropriate to ensure that steps to properly address conflicts are taken throughout the course of scientific investigation and to ensure that research ethics principles are not breached (e.g. regarding participants protection from harm) after permission of the study has been granted.

RIPs as an effective and fair research enterprise
RIPs differ in terms of structure, processes, objectives and outcomes. This suggests that there may be different but legitimate ways of addressing ethical disagreements among partners and supporting transparent and fair partnerships. Some of the strategies we list below may be appropriate for some RIPs or help them consider how they might be applied with some modification to support good practice in their own collaborative projects.

Addressing disagreements by relying on transparent processes and impartiality
a. Consensus-based approaches to decision-making: To ensure transparency and impartiality in partners' negotiations, RIPs may adopt one of the consensus-based approaches to decision-making listed below: Nominal group technique 18 is based on structured small group decisions followed by a shared voting or ranking exercise. This technique is useful when decisions need to be made quickly and everyone's opinion should be taken into account.
Delphi technique 18 is undertaken predominantly by a questionnaire followed by a group discussion. This approach takes into account diverging values and viewpoints among partners. It is especially useful in contexts where participants are not equal and are knowledgeable in different areas 33,34 .
Consensus development conference combines consensus with some form of metrics. Summary statements are debated in a meeting and then participants seek consensus on the most important of these statements 18,33 b. Neutral facilitators Another strategy to ensure that all partners have equally contributed to decision-making processes is by using a neutral facilitator to undertake the coordination and administration of partnership negotiations. Neutral facilitators are individuals who are able to listen to, respect and incorporate into the process different perspectives. In other cases, this role may be taken by an executive committee, an advisory group 33,35 , a steering committee 17 or an independent board of trustees. Neutral facilitators aim to ensure impartiality, and that potential conflicts are avoided, and partners' independence is not compromised 36 .
Supporting effective governance a. Partners' governance documents An important step to ensure the ethical integrity of research partnerships is to inform and develop RIPs' governance documents v based on the ethical considerations discussed earlier. Self-regulatory codes of conduct and principles are essential for RIPs' effective governance and accountability 9,19 . Governance documents should specify appropriate interactions among partners, who should be held accountable when misconduct occurs (e.g. all partners, the project manager, etc) and outline agreed procedures regarding decision-making, resolution of disputes, dissemination of research findings, data sharing, intellectual property, and others.
b. Legal binding contracts Developing governance documents into binding contracts among research partners can be another way to address potential and actual issues related to fairness, accountability and transparency. Relying on legal binding arrangements could be a practical step to formalise the roles and responsibilities of each partner as well as their expected contribution and remuneration 37 . A binding contract among research partners could help partners avoid confusion and misunderstandings, recognise each other's professional role and broader commitments and ensure that partners' obligations are met and harms that could potentially result from exploitative processes are prevented. Regulatory protections are also important to ensure that for each partner professional independence is maintained and that all partners are protected from coercion or other kinds of harm (e.g. reputational harm, compromise of academic freedom; involvement of people with first-hand experience of mental illness in processes they may be uncomfortable with, etc).

c. Consultants
Another strategy by which RIPs can improve the quality of their governance is by involving Individuals with relevant technical, ethical, administrative experience as consultants to provide organisational content expertise 16 . Consultants can help with coordination of the meetings, facilitate negotiations or provide training and supervision according to partnership needs 25 .

d. Shared management
In some cases, research collaborations are perceived as 'successful' when all partners take a role in managing the relationship 38 . A shared management model will be appropriate for RIPs relying on the equal contribution of all partners. In shared-management models each partner entity selects an individual to become a 'relationship manager', 'champion' or 'facilitator'. Relationship managers are dedicated to making the partnership a successful collaboration 39 and in some cases to maintain partners relationship following completion of a project.

Improving research processes and establishing good relationships among partners a. Sharing good practices within partnerships
The relationship of research partners is an essential part of ethical collaborative mental health projects. To form the foundation for trustworthy and ethical RIPs, sharing good practices and lessons learnt within RIPs is important. Opportunities for shared learning can facilitate transparent decision-making and relationship building within partnerships 40,41 and address bias and presumptions that partners may hold for each other.
b. Partnership evaluations Assessing the quality of partners' relationships in different RIP models and types of research is important to identify and address the unique challenges they present. Understanding how partners share information with each other and how they value each other's contribution in various types of RIPs may help partners identify possible insufficiencies in adopted strategies and potential and actual barriers in establishing meaningful partnerships in different contexts. Such evaluations can also help partners to appreciate the importance of creating the right platforms where they can meaningfully work together 42,43 (and share good practices and lessons learned as mentioned earlier).
Evaluations are also important to increase the quality and acceptability of the decision-making processes 33,44 and reflect on the progress made towards planned research goals 25 . This can take the form of formal evaluations 39 , regular reviews, compliance and ethics follow up tools 18

Conclusion
There are several benefits but also ethical challenges in RIPs. Ethical guidance is needed to prevent and address these challenges but also to promote the scientific and social benefits of these new research partnership models. The aim of this paper was to provide a platform for further articulation of ethical practices in RIPs rather than to provide an exhaustive action list for those involved in such partnerships. We claimed that to establish ethical and productive RIPs, robust ethical principles should inform clear guidance and practices. These principles were identified through a scoping review and critical analysis. We need however to note that a broader and more thorough review of the literature is needed to confirm or challenge our results. Based on our findings we proposed strategies that can support best practice in establishing fair and successful mental health research partnerships among academia, industry and people with experience of mental illness. We hope that this work will stimulate further discussion and encourage empirical work to assess whether and how a prospective ethical tool may promote ethical partnerships and support socially valuable mental health research.

Data availability
Underlying data All data underlying the results are available as part of the article and no additional source data are required.

Anna Chiumento
Department of Psychological Sciences, University of Liverpool, Liverpool, UK Many thanks for inviting me to review this article which presents a scoping review and the authors recommendations regarding the need for ethical guidance to support effective partnerships between the pharmaceutical industry, academia, and service users when conducting collaborative mental health research. Overall I found the article made some interesting points, but lacked clarity of focus and failed to present a sustained and persuasive argument of the need for additional ethical guidelines. Below I identify a range of overarching and specific comments for the authors to engage with to enhance their manuscript.
Overarching comments: In the background the authors make an effort to situate their paper in the mental health field, developing a case for the need to conduct a scoping review to develop ethical guidelines for collaborative mental health research. However, in its brevity, this background doesn't present why these additional guidelines are necessary. The authors for example allude to the complexities of mental health research being particularly important, but the reader is never informed of what these complexities are, nor why they present distinctive ethical issues. I realise there is another paper which the authors have written (and referenced -Lignou, Geddes & Singh (2020)) that explores this in detail, however more information is needed here to substantiate their position in this paper.

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Similarly this reader is acutely aware of the plethora of ethical guidelines already available, many of which are included in this articles scoping review. In light of this, I was struggling to see what was unique or distinctive about the particular framework the authors propose, and how this might help address some of the shortcomings of previous frameworks which seems to lie in the operationalisation or application of principles rather than the principles not already being identified in existing frameworks. The need for a new framework, and how this addresses the limitations of existing frameworks, needs to be made more explicit to identify the importance of this work.

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Relatedly, the authors seem to move between an argument for ethical / normative ○ framework, and the importance and role of trustworthiness (e.g. in the introduction stating "Here we propose a moral framework to guide research partners in designing, sustaining and assessing and ethical and trustworthy collaborative mental health research project"). Can support be provided for the role of trust in ethical research conduct / action, and how these are being brought together in the framing of this study and the conclusions drawn? Methods: I found the description of the study methods lacked detail which made it difficult to assess methodological rigor. I realise as a scoping review full systematic approach is not applicable, but it would be helpful if the authors could clarify whether they followed any guidelines, e.g. the PRISMA extension for scoping reviews. In addition, could the authors please address the following.
Identify the question they set out to address with this scoping review, and the aims and objectives for conducting this (which are mentioned on p.5 but should come in the methods section).
principles and follow fair practices". I am interested in the idea that there are "concrete ethical principles" which the authors appear to suggest would be a way to prevent poor practice or exploitation of partners -can this be explored further?
The authors also seem to have an implicit framing in mind of various levels at which ethical principles might operate, for example at the "organisational level" or partnership level. Could this be explored further, for example are the authors suggesting that some principles are specific to an organisation autonomous actions that might not apply or apply differently in a partnership context? ○ Similarly on p.6 under the principle of "respect" the authors identify physical, social, and sociological harm. Can you please clarify what is meant by sociological harm? Also given the focus on mental health could it be relevant to include emotional harm or distress here? As well as in the context of industry it could perhaps be important to include reputational harm (which may be a component of social harm)?
○ Discussion: Here the authors focus on proposing strategies for minimising potential or actual conflicts. I found this unexpected, and the relationship between the results of the review and the points in the discussion needs to be significantly strengthened -do these discussion points arise out of the scoping review or from elsewhere? I was not persuaded that this discussion added anything novel or useful, and may detract from the core focus of the paper which is on the need for additional ethical frameworks. Here were have a selection of other tools which may or may not be relevant in a range of circumstances, and does not seems to add anything to the existing knowledge or literature in this area.
As a more minor comment on p.7 the authors refer to enhancing ethics reviews -can you please clarify what ethics review this is referring to, research or clinical ethics? Relatedly, how do the issues in this paragraph, which largely appear to be governance related, fit within the scope and remit of an ethics committee more broadly?
Editing points: Please review footnotes for acronyms that are not defined elsewhere in the paper.

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References require some attention to ensure completeness -e.g. reference 41 appears to be missing the journal title, and only have the starting page number.
○ I found the acronym RIPs a little off-putting given the association in everyday English with "rest in peace".I'm not sure if others would have the same difficulty, but I would recommend that the authors consider an alternative shorthand. ○ I hope that these comments are useful to the authors in strengthening the clarity of this paper to ensure its contribution to the literature is fully realised.

Is the study design appropriate and is the work technically sound? Yes
Are sufficient details of methods and analysis provided to allow replication by others?