The Finding My Way UK Clinical Trial: Adaptation Report and Protocol for a Replication Randomized Controlled Efficacy Trial of a Web-Based Psychological Program to Support Cancer Survivors

Background Cancer survivors frequently report a range of unmet psychological and supportive care needs; these often continue after treatment has finished and are predictive of psychological distress and poor health-related quality of life. Web-based interventions demonstrate good efficacy in addressing these concerns and are more accessible than face-to-face interventions. Finding My Way (FMW) is a web-based, psycho-educational, and cognitive behavioral therapy intervention for cancer survivors developed in Australia. Previous trials have demonstrated that FMW is acceptable, highly adhered to, and effective in reducing the impact of distress on quality of life while leading to cost savings through health resource use reduction. Objective This study aims to adapt the Australian FMW website for a UK cancer care context and then undertake a single-blinded, randomized controlled trial of FMW UK against a treatment-as-usual waitlist control. Methods To an extent, our trial design replicates the existing Australian randomized controlled trial of FMW. Following a comprehensive adaptation of the web resource, we will recruit 294 participants (147 per study arm) from across clinical sites in North West England and North Wales. Participants will have been diagnosed with cancer of any type in the last 6 months, have received anticancer treatment with curative intent, be aged ≥16 years, be proficient in English, and have access to the internet and an active email address. Participants will be identified and recruited through the National Institute for Health Research clinical research network. Measures of distress, quality of life, and health economic outcomes will be collected using a self-report web-based questionnaire at baseline, midtreatment, posttreatment, and both 3- and 6-month follow-up. Quantitative data will be analyzed using intention-to-treat mixed model repeated measures analysis. Embedded semistructured qualitative interviews will probe engagement with, and experiences of using, FMW UK and suggestions for future improvements. Results The website adaptation work was completed in January 2021. A panel of cancer survivors and health care professionals provided feedback on the test version of FMW UK. Feedback was positive overall, although minor updates were made to website navigation, inclusivity, terminology, and the wording of the Improving Communication and Sexuality and Intimacy content. Recruitment for the clinical trial commenced in April 2021. We aim to report on findings from mid-2023. Conclusions Replication studies are an important aspect of the scientific process, particularly in psychological and clinical trial literature, especially in different geographical settings. Before replicating the FMW trial in the UK setting, content updating was required. If FMW UK now replicates Australian findings, we will have identified a novel and cost-effective method of psychosocial care delivery for cancer survivors in the United Kingdom. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN) 14317248; https://www.isrctn.com/ISRCTN14317248 International Registered Report Identifier (IRRID) DERR1-10.2196/31976

All appropriate 6. CONCLUSION This is a very well considered and well articulated proposal. it tapps into an area that requires research that I understand the team applying can deliver on. The proposed time frame seems very realistic. I believe this is a very important piece of research and commend the application. If Yes, please state the dates of collaboration and/or publications within the last five years.
I am aware of the applicants' work in the field. b) How do you rate the research standing and ability of the applicants to carry out the proposed work?
They applicants have produced high quality outputs, ensuring a rigorous approach to their research.

IMPORTANCE
How important to the understanding of cancer are the aims of the proposed work? In what way are they important?
The aims of the proposed work are important, as distress and anxiety are common during treatment for cancer, and effective evidence-based programmes are lacking. However, I question whether the proposed programme would be of greater benefit post-six months following diagnosis/treatment. This is often the time (once active treatment has ceased) when survivors are particularly struggling. I wonder whether this may also be why effective findings were not found in more outcomes in the Beatty et al paper (although I also appreciate this may be due to the nature of the control condition). Nonetheless, helping relieve psychological distress among survivors is of grave importance.

ORIGINALITY
Have others attempted to answer the same questions (or are they doing so now)? If so, please elaborate and indicate whether the work needs repeating or if the proposal offers anything new.
Obviously, this trial is a replication of a previous study; therefore, it is not necessarily original. However, it involves the adaptation of the programme. Based on the findings from the previous study, the programme warrants a larger RCT, as the programme has been developed in a rigorous evidence-based manner, and indicated promising effect sizes. However, whilst it is not an original programme, it would require adaptation for the UK context, and could offer benefits to the cancer survivors accessing the NHS.

METHODOLOGY
Is the Plan of Investigation likely to yield important results and, if so, on what time scale? Please give reasons and feel free to suggest improvement.
The proposed methodology has been well thought out, and adopts a rigorous approach -ensuring that the adaptation/development work is not rushed. It is likely to yield important results, in terms of whether the programme is effective, by the end of the 2.5 years. What has not been accounted for in the timeline, and should be, is time to implement further changes to the programme based on the qualitative findings. This is important, particularly if the programme is to be rolled out.
A concern of mine also relates to evaluating the programme among all cancers, regardless of the diagnosis. Whilst there will be commonalities of experiences across the different cancer groups, there is likely to be concerns specific to the cancer itself which will not be addressed, or are irrelevant to some. The prior Beatty et al evaluative study was primarily made up of breast cancer patients, and therefore is not necessarily representative of all other cancers. The more generalised nature of the material (i.e. not specific to cancers) may also be another reason why effective findings were not identified across more outcome measures. It is therefore difficult to know whether the larger sample size proposed in the present study would overcome this problem, and lead to significant findings.

LEVEL OF FINANCIAL SUPPORT
Please comment on the costs requested for: This seems reasonable.

(b) Expenses
These seem to have been reasonably calculated.

(c) Equipment
This seems reasonable for the cost of two computers/laptops. If Yes, please state the dates of collaboration and/or publications within the last five years.
d) How do you rate the research standing and ability of the applicants to carry out the proposed work?
The research team that has been assembled is excellent. A range of disciplines are represented including health psychology, oncology, health economics and medical statistics. Within this, the research team demonstrates considerable experience of online psychosocial interventions which will be invaluable for the current study. The international collaborative nature of the team which includes the authors of the original Australian intervention is also a benefit.
The publication records of the research team demonstrate an ability to publish high quality papers related to psycho-oncology. Members have also secured funding for complementary studies, although in some cases these are small grants.

IMPORTANCE
How important to the understanding of cancer are the aims of the proposed work? In what way are they important? As outlined in the study, distress among cancer survivors remains burdensome both to the individual in terms of quality of life and to the health service in terms of increased costs. There is currently little available to support psychosocial wellbeing of people diagnosed with cancer.
Although not addressed in this study, distress is likely to also be related to adherence to adjuvant medication and lifestyle modifications that may be required to reduce recurrence after the primary cancer is treated. A number of recently published studies have identified that depression and anxiety are important issues among cancer survivors and often constitute an unmet need, particularly as patients are discharged into open access follow-up where this type of non-clinical outcome is difficult to monitor and address by the clinical nurse specialists. An online intervention may therefore be particularly feasible and desirable for this population.

ORIGINALITY
Have others attempted to answer the same questions (or are they doing so now)? If so, please elaborate and indicate whether the work needs repeating or if the proposal offers anything new.
There is a lot of research currently being undertaken in the area of e-health in psychooncology. However, this application is noteworthy because of the efficient design of testing an intervention which has already been developed in a different country. This will provide both important replication data and provide the opportunity to tailor the intervention to be culturally specific to a different healthcare system. As the original trial showed improvements in quality of life and distress over time but no group differences, this study would be improved by including both an active control (in line with the previous study) and TAU in order to determine true intervention effects. This would be beneficial not only for the local implementation of the intervention but also for the global perspective. Overall, the methodology plan is suitable to trial this type of online psychosocial intervention. The timescale is mostly appropriate, although if ethical approval is required from the institution before sponsorship can be agreed for the NHS HRA ethics application, then this may require some additional time -time for amendments to add additional recruitment sites if necessary should also be considered as this can take up to 3 months. The costs and time that have been allocated to modify an existing intervention rather than design a new one are realistic and represent good value for money.
There are a number of positive highlights from the proposed study. The research team have designed a high quality replication of a previous study which showed promising results in Australia. Replication is an important and often overlooked part of the scientific process. A good recruitment strategy has been proposed and the researchers have evidenced that they have worked with the sites successfully in previous studies. As the study would be eligible to be listed on the CLRN portfolio and the recruitment process is not too onerous on the research nurses, this should be a successful strategy. The researchers have also embedded high quality PPI into the study from writing the application through to dissemination with an expert patient co-applicant.
There are some comments on the methodology that could be addressed; 1) The study on which this trial is based showed no significant differences between groups on the primary or secondary outcomes, which the authors postulate is because of the active control. The treatment as usual (TAU) group proposed for the current study appears to not be a true TAU and may weaken the effect. Given the results of the previous study in Australia, it would be useful to employ a three arm trial of intervention, active control and TAU to determine, although that would require a larger sample size. 2) As all types of cancer are eligible for the study, this may dilute the effect of the intervention. The content could be more specific and tailored to particular cancerspecific issues which may increase the effectiveness. The researchers state that "efforts will be made to balance cancer types between groups" but it is unclear how this will be done. Will stratification by cancer type be carried out? 3) Participants will not be screened for distress. Although I understand that the researchers intend to replicate a naturalistic setting, the lack of screening will minimise the potential effectiveness of the intervention; i.e. if a participant is not distressed then it is not possible to improve this outcome. Although an online intervention, resources would be required to implement the intervention into usual care and therefore it may be more prudent to concentrate on those who most require it. Alternatively, the sample size calculation should take into account a suitable sensitivity analysis to determine the effects for those most distressed, which does not currently appear to be the case. 4) There is currently little information about how distress and series adverse events will be detected and how the routes for referral. Will content of the website be monitored, and if not, will this be made clear to participants. These issues however will be covered as part of the ethics application. 5) Emotional factors are well covered in the measurement of outcomes, however cognitive factors (e.g. illness perceptions) are not. These are likely to be related to some of the outcomes of interest and process variables. 6) Recruitment options are sensible, however the researchers may consider including more funds to cover advertisement for online recruitment and postal data collection.

LEVEL OF FINANCIAL SUPPORT
Please comment on the costs requested for: Costs are mostly appropriate, however the researchers may consider including more funds to cover advertisement for online recruitment and postal data collection.
It would be appropriate for the PI and principle researcher to visit the intervention development team in Australia and the costs included for this are justifiable. However, the backfill for the one week of PI team could be reconsidered.