Conclusions

Objectives

The aim of understanding the issues for cancer survivors and then iteratively developing an intervention requiring limited resources was achieved.

Implications of our findings for future research and practice in quality of life for cancer survivors

This is one of the few trials of brief multidimensional support for cancer survivors who are likely to have persistently lower quality of life in primary care and documents improvement in quality of life among participants given detailed evidence-based generic lifestyle advice. Comparing the Renewed interventions with generic advice there was limited evidence of between group differences in overall quality of life at 6 months. However, there were small differences between the supported Renewed intervention and the generic advice group by 12 months. Potentially more important and longer-term differences for both the Renewed groups compared with generic advice were found in global rating of health, symptom management, and enablement by 12 months.

Overall, quality of life improved both for participants encouraged to use a link to the NHS LiveWell website (Generic advice) and for participants given access to the Renewed interventions. The improvement in all groups is unlikely to be a reflection of the natural history in our sample (where the mean time since treatment was 4 years), since groups with poor HRQoL remain consistently poor in this population after 2 years,42 and in particular groups with low quality of life do not improve. We anticipated a long-term impact, but the primary analysis time point was chosen as 6 months because that was the timescale previous systematic reviews had reported.37 There were no significant differences between groups overall by 6 months, although participants with prostate cancer in the support group improved significantly more than those given the generic healthy lifestyle link.

By 12 months the generic advice group had stopped improving but improvement was maintained in the intervention groups, significantly so for participants in the support group. Most of the effect was seen in the subgroup with prostate cancer which may be important given the significant stigmatisation and need for support in this patient group.43,44 The results for symptoms subscales demonstrated a small but significantly improved rating of global health at 6 months compared with the generic advice group, but limited evidence of between group differences in the other subscales. By 12 months both renewed groups continued significantly to improve ratings of global health compared to the generic advice group and there were also modest but significant between group differences in several other functional or symptom subscales, and enablement. Of the 14 subscales addressing function or symptoms (excluding the financial subscale which the intervention could not address), all but one subscale demonstrated improvement in the Renewed group compared to the generic advice group. Three out of the 14 were significantly different; for the Renewed plus support group all 14 subscales improved compared to the generic advice group and 7 of them were significant. This makes chance a very unlikely explanation. Most important of the subscales is arguably the improvement in self-rated global health, which improved significantly at 6 months and the effect was greater by 12 months. Self-rated global health is clinically important, since it has consistently been shown to be a strong predictor of mental health, physical health and mortality in the longer term.45–51 The symptoms consistently improved compared to generic advice in both Renewed groups by 12 months were dyspnoea and constipation, also suggesting these were not chance findings. This is likely to be due to the development of specific, salient, advice tailored to address cancer survivors’ issues19 to better enable participants to manage their symptoms. The finding that enablement improved with Renewed (both with and without support), albeit with less complete data, is probably also important in its own right since in the ColoREctal Wellbeing colorectal cohort confidence to self-manage was highly predictive of subsequent health and well-being outcomes.52 Mean NHS primary care costs were lower in Renewed and Renewed plus support groups (–£141, –£63, respectively) which resulted in both interventions being cost-effective based on standard National Institute for Health and Care Excellence thresholds. The modest longer-term improvement over and above the impact of detailed generic advice in most subscales particularly the global health subscales suggests that Renewed is a useful adjunct to generic advice, particularly given the primary care NHS cost savings.

There is some evidence from systematic reviews of trials that yoga, physical exercise more generally, cognitive–behavioural therapy, mindfulness-based stress reduction programmes, and dietary interventions can improve quality of life37,53–59 but very little evidence of benefit at 6 months from multidimensional home-based interventions59 and no evidence of benefit in the longer term. Although cohort studies suggest diet may impact recurrence and mortality,60 the evidence from trials is less clear.53,61 To our knowledge, there has been no trial with longer-term follow-up of robustly developed, brief multidimensional support for cancer survivors in primary care for pragmatic applicability in everyday practice.

Thus, the current study provides reasonable evidence that a novel bespoke intervention to support cancer survivors could be integrated into current practice since there are some longer-term benefits with lower costs to the NHS. However, all trial participants by definition had to engage with the trial and trial procedures, and so may not represent the wider patient population, and all were followed up with questionnaires and with phone calls where questionnaires were not returned. This could be mimicked in routine practice by brief follow-up contacts, but whether the effects in routine practice will turn out to be as useful as the current trial suggests requires a larger implementation study.

The contribution of patient and public involvement

The PPI involvement throughout this programme aimed to ensure that patients’ needs and preferences were understood and accommodated wherever possible within the research. This included ensuring that the intervention itself was useful, reassuring, persuasive and motivating and that the research studies were accessible and feasible for people to participate in. The PPI group were an integral part of all stages of the research cycle. They helped design the research, optimise the research strategy (e.g. suggesting ways to optimise recruitment), helped with the interpretation of the study findings and with dissemination of these findings. PPI members contributed to larger meetings with the full research team, but also met with two researchers in smaller meetings to discuss issues in more depth. They also provided written input on the study documentation and intervention.

Our work with PPI contributors made a significant contribution to the CLASP research programme. Box 1 provides specific examples of how our PPI group improved the research.

1. Improving patient study documents to promote study engagement and patient experience.
   • - Improving clarity of statements in the Participant Information Sheet for the RCT to make the description of the intervention groups and procedures involved easier to understand.
2. Intervention design.
   • - Choosing the name of the intervention (Renewed).
   • - Choosing between design mock ups for the look and feel of the Renewed website.
   • - Suggesting the number of human support appointment contacts and frequency that would be most suitable.
   • - Suggesting factors that might motivate patients to engage in behaviour change that were incorporated into the motivational quizzes (e.g. within Getting Active).
3. Intervention optimisation.
   • - Testing the Renewed intervention and highlighting places that were confusing or harder to understand or navigate, enabling optimisation.
4. Providing a PPI perspective on findings.
   • - The PPI group helped interpret the findings from the qualitative optimisation studies, main trial and process evaluation. For example, some highlighted that the intervention might have been more successful in those with prostate cancer because this group receive less support after discharge from primary treatment than those with bowel/breast cancer.
   • - Suggesting additional questions to explore within the analyses – for example two PPI members suggested examining whether uptake of nurse support was different across cancer types within the process evaluation (it was not, but this was a useful avenue to explore).
5. Dissemination.
   • - Inputting to discussions about how the intervention should best be disseminated to reach members of the public and those who have survived cancer.
   • - Inputting into all of the academic publications resulting from this programme of research.
   • - Volunteering to help disseminate the research findings within workshops for cancer survivors.

Strengths, successes, limitations and challenges

Strengths and successes

The complex intervention was developed robustly for a range of cancer survivors with a user centred approach, the Person-Based-Approach, which has been shown to be effective for the development of other complex behavioural interventions with brief support.14,62,63 This is one of the largest trials to assess the impact of brief support to cancer survivors and addressed contrasting cancers. The method of invitation (a non-specific ‘cold-calling’ invitation to capture most potentially eligible patients) was largely successful, but inevitably resulted in a relatively low take up; reassuringly only 25% (2649/10,697) declined due to lack of internet access. This is similar to the national figure of 20% for 64–75 years old in 2018 (https://www.ons.gov.uk/businessindustryandtrade/itandinternetindustry/datasets/internetusers; accessed 6 March 2025). The sample had high levels of comorbidity as would be expected,17,64,65 and among those assessed for eligibility only 6% (291/4858) of eligible participants declined which supports the generalisability of the trial.

Limitations and challenges

A small percentage of ethnic minority participants would be expected for the target population of patients; nevertheless, fewer were recruited than census data would suggest, which reflects the difficulty of recruiting in ethnic minority areas. Recruitment for participants with colorectal cancer was an unexpected challenge and for no clear reason that we could discern; hence we had limited power for the colorectal cancer subgroup. We also did not control for any variability in initial cancer treatment, but the size of the study means that that randomisation should have balanced out possible confounders. Developing a complex intervention suitable for supporting a variety of cancer survivors was certainly a challenge, but the flexibility in Person-Based Approach made this possible. A major challenge in designing the research was the choice of outcome measure – which needed to be validated and brief enough to make completion rates robust. For such a brief intervention the impact on quality of life would be expected to be small, so the subgroups overall are arguably underpowered, and the choice of overall EORTCQLQ score could be criticised as a blunt instrument for such low intensity interventions. In retrospect a measure more suited to cancer survivors in primary care settings would have been better or to consider using other measures of global health.

The sample only included those with lower quality of life scores initially, so regression to the mean is one possibility for the change in the generic advice group. However, in our sample, most of whom were beyond 2 years following primary treatment; quality of life would be expected to be stable42 with low quality of life consistent over time.52 We found that if anything the effect of intervention was more pronounced for those 4 years or more after finishing primary treatment. The ‘generic’ advice to the NHS website has a lot of click-throughs to more in-depth advice and support for people (e.g. physical activity programmes or mental health programmes that people can follow). This is more input than many cancer survivors would routinely receive in primary care and may be an important reason behind the useful improvement seen in the control group, and which would be expected to reduce any differences between groups. Two to three per cent of the study population compared with 6% from the 2021 census were non-White, and which reflects the difficult of recruiting in ethnic minority areas.

For the health economic analysis, although the first change in prescribed medications were costed and for subsequent changes the average cost per patient of the first change was used (due to the huge variability in recording of medication), this probably had little impact on overall cost per patient, as medications accounted for a low proportion of total costs. Inclusion of all service use during the trial led to possible overestimation of costs given that some such service use had no plausible connection to the intervention, and as expected the main reductions in cost were observed in primary care, but even using the total costs both interventions incurred lower costs than the control group. A societal analysis was not performed but since the NHS analysis suggested the interventions were cost-effective, it is likely that a societal analysis would provide even stronger evidence of cost-effectiveness.

Summary and recommendations for future research

Recommendations for future research

The cost-effectiveness and benefits for symptom management self-rated health for both Renewed interventions suggest that an implementation study is the next step.

To consider using and/or developing more sensitive primary outcome measures among cancer survivors, particularly for briefer, low resource interventions – since the overall EORTCQLQ-C30 summary score is not sensitive to change, in contrast to both symptom subscales and self-rating of health.

To develop QALY measures that capture the benefit to QoL for low-intensity, low-resource interventions among cancer survivors given that neither the EQ-5D-5L nor the EORTC-8d reflected important changes in patients’ self-rating of health.

To explore possible barriers for ethnic minority groups, and individuals with different cancer types to participate

Implications for health care

Cancer survivors with lower quality of life given detailed generic online support improve significantly, including those where the primary course of treatment was several years previously – where improvement in quality of life would not be expected. Providing a robustly developed website to address peoples’ support needs, with minimal additional resource implications, is likely to provide modest but significant further longer-term improvement in enablement, symptom management and most importantly self-rated global health, and with lower NHS costs, particularly costs in primary care.