The PCPI was organised and run jointly by the two patient support organisations CAUK and Cavernoma Ireland, under the responsibility of the Trustees and Chief Executive of CAUK. We created a diverse PAG of 12 members ranging in age and including patients, parent carers and unpaid carers which reported to the TMG and TSC. The PAG met via Zoom (Zoom Video Communications, San Jose, CA, USA) every other month during the recruitment phase, and then as required. The chief investigator, trial manager and Dr Julia Wade (QuinteT) and the chief executive of CAUK attended PAG meetings as observers. The work of the PCPI input varied according to the phases of the trial.
Funding application
In 2015, CAUK co-ordinated a James Lind Alliance Priority Setting Partnership of cavernoma patients and clinicians ‘Priorities for research into cavernoma’ that placed the subject of the CARE trial as its top priority. CAUK ran a focus group in July 2019 to consider the overall design of CARE.
Cavernomas A Randomised Effectiveness start-up
Cavernoma Alliance UK developed comprehensive resources on its website with input from the chief investigator and QRI researchers. This was constantly updated and included: Frequently Asked Questions, Recruitment & Eligibility, Information Leaflets, Importance of Randomised Controlled Trials and Contacts. The site had two explanatory videos (https://cavernoma.org.uk/care-study/).
The PAG provided feedback on the patient information leaflets. A key focus of the PAG input was in shaping the content and presentation of a table included in the participant information leaflets showing processes, risks and benefits involved with each arm within the CARE pilot RCT (Table 4). The PAG shaped the content and presentation of information in both the short and supplementary adult participant information leaflets. This content, in turn, fed into codevelopment with the trial team of other participant information leaflets (child with capacity, children 0–5 years, children 6–10 years, parent guardian) shaped by advice from parents with children. The main concern of feedback from the sponsor and REC was the retention of adults who may lose mental capacity during the trial. Other major topics discussed were outcome measures and how the helpline should address referral to study sites. The PAG expressed its gratitude for the spirit of collaboration that Professor Salman brought to the meeting, with the emphasis of reaching consensus.
| Medical and surgical management | |||
|---|---|---|---|
| Medical management | Neurosurgery | Stereotactic radiosurgery | |
| What may be involved? | Treat symptomsPrevent seizuresRehabilitationBrain scan | Treat symptomsPrevent seizuresRehabilitationBrain scan | Treat symptomsPrevent seizuresRehabilitationBrain scan |
| Hospital admission for daysGeneral anaestheticOpening in the skullOperation to remove cavernomaFollow-up brain scanMust not drive for 6 months | Hospital attendance for a dayAnaesthetic not neededHead fixed in a temporary frameFocused radiation given onceFollow-up brain scans | ||
| What are the possible benefits? | Bleed/stroke risk reduces as time passesAvoids risks of neurosurgery or radiosurgery | Risk of bleed/stroke lower if cavernoma removedLess worry about symptoms returning | Risk of bleed/stroke may be lower if cavernoma stabilised, but these benefits are uncertainLess worry about symptoms returning |
| What are the possible risks? | Future bleed/stroke due to cavernoma | Bleed/stroke due to neurosurgery | Bleed/stroke despite radiosurgery |
| Can be mild | Can be mild | Can be mild | |
| May be disabling | May be disabling | May be disabling | |
| Rarely be fatal | Rarely be fatal | Rarely be fatal | |
| Risk higher for cavernoma in brainstem | Risk higher for cavernoma in brainstem | Risk higher for cavernoma in brainstem | |
| Epileptic seizures, which may be difficult to controlCavernoma remains in the brain, so the risks of stroke and seizure may never go awayWorry about symptoms returning | Epileptic seizures may not go awayComplications of treatment (e.g. infection or damage to brain around the cavernoma)Cavernoma may come back | Epileptic seizures may not go awayComplications of treatment (e.g. damage to brain around the cavernoma)Cavernoma not removed | |
All those answering the CAUK helpline during the recruitment phase received training from the QRI team (May 2021). This included tips on how to present information in a way that conveyed equipoise, to respond to people who expressed preferences and explaining the reason for randomisation.
Recruitment
The primary role during the recruitment phase was to promote CARE to potential participants:
- CAUK ran a telephone and e-mail helpline throughout the CARE recruitment phase, supporting trial candidates, enrolled participants and unpaid carers by providing objective and unbiased information, alongside emotional support.
- The helpline team attended refresher training courses delivered by the QRI and CARE trial teams in November 2021 and February 2022.
- The co-chief investigators gave an introduction to the CARE study to the annual meeting of CAUK’s Annual International Forum in June 2021 with very positive feedback.
- CAUK’s outreach community worker posted regular updates and recruitment promotions on Facebook [Meta Platforms, Inc. (formerly Facebook, Inc.) Menlo Park, CA, USA], Twitter [X Corp. (formerly Twitter) San Francisco, CA, USA] and Instagram (Meta Platforms, Inc Menlo Park, CA, USA).
- CAUK’s monthly newsletter, circulated to all members of CAUK (2800 in 2020, 3500 in March 2023), had a CARE update.
Follow-up
There were no meetings of PAG during the follow-up phase of the trial, although a representative from each of CAUK and from Cavernoma Ireland continued to attend meetings of the TMG and the TSC.
Documentation
The PAG met twice to provide feedback on late drafts of the following documentation: QRI report, clinical trial report, NIHR synopsis and the plain language summary. The PCPI representatives led on the creation of a video abstract to disseminate results to the public, participants, patients and carers.
Study results
Helpline
The helpline responded to 253 inputs (calls 34%, e-mails 64% and 2% other) from 131 individuals, of whom 24 were seen by a study site team. Of the calls/e-mails, 40% were for general information, 36% for how to take part and 7% concerning special problems of referral to a study site with an assortment of other matters. The average time for each input was 23 minutes, that is, roughly 100 hours in total. As shown in Tables 5 and 6, 58% of those calling the helpline heard about CARE through CAUK sources.
| Source | N | % |
|---|---|---|
| CAUK website | 96 | 39 |
| Caller’s neurologist | 26 | 11 |
| CAUK social media | 24 | 10 |
| Helpline chat | 20 | 8 |
| Caller’s neurosurgeon | 7 | 3 |
| Trial site | 4 | 2 |
| Team | 4 | 2 |
| Other | 65 | 25 |
| Source | N | % |
|---|---|---|
| CAUK website | 142 | 39 |
| Participant information leaflet | 126 | 34 |
| Site study team | 24 | 7 |
| CARE website | 9 | 2 |
| None | 29 | 8 |
| Other | 36 | 10 |
Social media
Facebook, Instagram, Twitter and LinkedIn (LinkedIn, Sunnyvale, CA, USA) were used as communication channels to reach the widest possible audience, to support recruitment to the project. Engagement was strong throughout with an uptake in helpline enquiries after each post (Figure 1).
FIGURE 1 Helpline calls over time. (Figure not reproduced here; see the original article.)
Website
The CAUK webmaster estimated that he spent about 8 week’s work, spread over the 3 years of the project, on work maintaining the website. Most of this work was paid within the terms of his contract with CAUK (i.e. not funded from CARE study funds).
Discussion and conclusions
The attention paid by the TMG to the PAG’s comments on the various documents it considered suggested to the PAG that it had a significant input into their quality for patients and carers. All the PAG input was given true consideration, and most adopted. The efforts of the PAG brought the CARE pilot trial to the attention of members of CAUK and Cavernoma Ireland on a regular basis via social media and monthly newsletter and to a wider audience via the CAUK website. Data protection and clinical confidentiality issues prevented CAUK being able to report which callers to CAUK helpline subsequently contacted a CARE pilot study site and whether CAUK input influenced the decision to take part. Qualitative data captured by the QRI team included positive comments about the support received from CAUK from people choosing to take part. Some CAUK members reported to the helpline having contacted CARE sites, and we asked those patients to comment on the contribution the PCPI/CAUK had on their decisions to take part in CARE (Table 7).
| Comment | Respondent |
|---|---|
| ‘I also went onto the Cavernoma Alliance UK website which I found very informative and which led me to other associated sites, including the Edinburgh University and Prof Salman’s involvement. From the CAUK website I was made aware early on that there were many other cavernoma sufferers with much worse symptoms than mine, which made their life very difficult’‘My contact with CAUK was always helpful and supportive. My questions were always answered and I was put in touch with parents who could also support me. If I had queries as to how CARE study would proceed I was given extra information. Or if I had not heard back from the hospital I was given support in prompting the hospital to make contact with me, etc’ | Took part and was randomised to intervention. Had neurosurgeryParent of child who joined the study but later opted out |
| ‘My contact with CAUK was helpful. They pointed me in the correct direction and outlined a bit about the study’ | Took part and was randomised to stereotactic radiosurgery, delivered outside the target 3-month window |
| ‘Although there was plenty of information on the CAUK website, it was useful to chat it through. It was particularly relevant to me … that CAUK was involved in the RCT as a partner, and reassuring that I could get in touch if I needed to. I also attended the online presentation from Prof Salman in summer 2023 (by which stage I had already had surgery), organised by CAUK and was pleased this was made available’ | Took part and was randomised to intervention. Had neurosurgery |
| ‘My contact with CAUK was very helpful to understand the specialists in the areas and options for surgery’ | Decided not to take part in the study |
| ‘[My contact with CAUK] was extremely helpful in two main ways. Firstly, being able to speak to someone that could provide support and understanding during such a stressful time when the way ahead was very unclear made a huge difference. Especially when there was some time to wait for hospital appointments and tests to be organised. Secondly the knowledge and information provided helped to increase not just my understanding of what might be happening but also possible ways forward. It was also very helpful to me to take part in the focus group as this brought me into contact with other people who had been impacted in many different ways by cavernomas and also to hear about the plans for future studies’ | Decided not to take part in the study |
| ‘[My contact with CAUK] was helpful in the fact that the team at [site] have said I do not have any cavernoma and that the lesions are likely to be amyloid deposits. I had all my original MRIs at [site]. The CARE study MRI was carried out in [site], I understand they are better MRIs. I wish I had known this at my original contact with [site], as I would have asked for my MRIs to have been carried out in [site]. This would have saved months/years of worry for myself and my family’ | Asked to take part, but then found not eligible |
Reflections
What went well from a patient and public involvement perspective was the role played by CAUK and Cavernoma Ireland in supporting patient recruitment, retention and compliance through the helpline, website and other communication channels. The PAG was also gratified by the willingness of the TMG to incorporate their feedback and ensure patient information was accessible and inclusive.
What was problematic, because it was not anticipated by PCPI representatives, was the delay to CARE study sites opening, in particular the lack of study sites opened in central England in the first year and no study sites opened in Ireland. This was, in part, a consequence of the impact of COVID-19 on research in clinical establishments and is documented in the CARE pilot trial publication.40 CAUK’s promotion of CARE started in a major way in July 2021, yet the first site did not open until the end of August 2021. This meant that early on, people contacting the helpline, and people to whom CAUK was promoting CARE, had no easily accessible study site when they were most geared up to considering CARE. CAUK could have also benefited from having more consistent guidance on how to arrange for an interested patient to contact a study site in England.