Patient comprehension is an important component of the informed consent process within clinical research (Ruske et al, 2021). Nevertheless, studies have indicated that clinical trial patients remember little of the information that is discussed during the informed consent process, and their level of understanding around essential information is often overestimated (Ruske et al, 2021). Systematic reviews into the informed consent process have outlined that the level of patient knowledge gained from informed consent is frequently inadequate and that further educational interventions need to be developed (Castillo et al, 2021).
There has been longstanding criticism of informed consent within clinical research, and it is often seen as a process that meets only the regulatory requirements imposed, rather than a truly ethical process that produces informed and voluntary participation within clinical research (Wexler et al, 2022).
The literature consistently reports a variety of challenges related to the sheer volume and complexity of information that patients receive during the informed consent process (Svobodova et al, 2022). Millum and Bromwich (2021) stated that patients are often given extremely detailed information; however, this does not consistently ensure the development of a high level of comprehension of the full nature and implications of the clinical trial.
Researchers have proposed that the informed consent process in cancer clinical trials has even more limitations, and that disease severity can play an important role in patients' decision-making process (Castillo et al, 2021). It is commonplace that cancer patients are eager to gain access to a potentially life-changing or life-saving medical treatment, which can influence their decision about whether or not to enrol in a clinical trial (Halpern et al, 2019).
Research by Zhang et al (2019) suggested that to truly improve participants' clinical research knowledge, informed consent educational ‘supplements’ are required. Olver et al (2009) proposed that providing additional pre-consent educational resources that explain the practical requirements of clinical trials is key to allowing an informed decision about participation to be made. Several studies have identified the need for interventions to improve patient understanding within the informed consent process for clinical trials (Bhatt, 2015; Lentz et al, 2016; Kraft and Doerr, 2018). These studies demonstrated that providing patients with additional written information and audiovisual programmes around the basic concepts of clinical trials prepared patients for initial clinical trial discussions as well as improved their understanding of clinical trials (Bhatt, 2015; Lentz et al, 2016; Kraft and Doerr, 2018).
The emergence of internet technologies, such as educational websites, as novel methods for enhancing informed consent have shown promise in patient education. Fraval et al (2015) suggested that online interactive websites can be tailored to patients' specific educational learning styles to enhance informed consent in a way that written documents cannot. Togaç and Yılmaz (2021) proposed that, within the informed consent process, online audiovisual educational resources can reduce deficiencies of understanding of complex information, in a more effective manner than the more traditional written educational resource approaches.
Further research (Simonds et al, 2017; Marcus et al, 2018) has suggested that multimedia interventions can prove useful in improving patients' understanding of the objectives of cancer clinical trials. They also have the potential to reduce the anxiety that is often related to clinical trial participation.
Background to the study
This original research was centred in the specialty of early phase cancer research, the branch of clinical research that focuses on phase one and phase two clinical trials:
- Phase one clinical trials usually aim to find the best dose of a treatment, its side-effects and what happens to the treatment in the body (Cancer Research UK, 2022)
- Phase two clinical trials usually aim to check the best dose of treatment, find out more about side-effects and examine how well the treatment works (Cancer Research UK, 2022).
The aim of this research was to explore the impact of a patient co-designed educational intervention for newly referred early phase cancer clinical trial patients.
The driving force for the development of this study were key findings revealed from a service evaluation project. This had highlighted that patients had gained minimal comprehension of what early phase clinical trials were, and what they might entail during this initial stage of the referral pathway (Hood, 2020). Findings indicated that a lack of comprehension led to misconceptions about what these trials were, which in turn increased feelings of anxiety and stress among patients and their family members (Hood, 2020).
Misconceptions or misguided beliefs around the purposes of early phase clinical trials are frequently reported among advanced cancer patients (Halpern et al, 2019). Asher et al (2022) stated that misconceptions are undoubtedly linked to the cultivation of unrealistic expectations of what these type of clinical trials may offer. Instead of understanding that this research focuses on safe dosage and the side-effect profile of an experimental treatment, patients often view early phase trials as an opportunity to cure their cancer (Cook et al, 2015).
As part of this research, an educational intervention, involving a website and booklet, were created for use at hospital sites that referred patients for an early phase clinical trial, to support patient education. Pre- and post-education interventional data collected were examined for this article, to review the impact of the intervention on cancer patients' experiences of being referred for such a clinical trial. The research took place in 2020, during the COVID-19 pandemic (Hood, 2023).
Method
Aim and objectives
The objective of this research was to explore using and building on findings from a completed service evaluation project around the development and use of an educational intervention for newly referred early phase cancer patients. This study examined the impact of this patient educational intervention within the clinical pathway for patients who were referred for an early phase oncology clinical trial.
The aims were:
- To understand the experiences of patients who have been referred for an early phase clinical trial pre- and post-intervention
- To investigate if the intervention reduced anxiety levels in newly referred patients.
Design
The study employed a pre- and post-interventional convergent mixed-methods design. The Generalised Anxiety Disorder Assessment (GAD-7) questionnaire (Williams, 2014) was used to measure the anxiety levels of cancer patients, while semi-structured interviews were employed to examine the patients' experiences. Thematic analysis was used to examine interview transcripts and develop themes (Braun and Clarke, 2012).
Patients who presented with a GAD-7 score of 10 or greater were referred to an NHS psychological therapies service. However, due to the pandemic, access to this service was limited.
Ethical approval
Ethical approval for this study was obtained from the Health Research Authority in July 2020 (Integrated Research Application System (IRAS) Project ID: 279203).
Sample
Participants were identified from the cancer clinical trial research unit of a regional cancer centre within an NHS foundation trust.
Inclusion criteria
Patients meeting the following criteria were included in phase one of the study:
- Men or women aged 18 years and above
- Patients with a confirmed diagnosis of advanced cancer
- Patient attending their first early phase oncology outpatients' appointment. For post-intervention patients only:
- Patients who had access to the educational intervention prior to attending their first early phase clinical trial appointment.
Exclusion criteria
The following patients were excluded from the study:
- Patients who had previously enrolled or taken part in an early phase clinical trial.
Education intervention
A booklet and audiovisual website were co-created by the researcher and a cancer Patient and Public Involvement (PPI) group. All of the information provided in both resources had been identified within a 2017 service evaluation (Hood, 2020). This had identified the essential information that patients and their family members considered would be useful to know before an initial early phase clinical trial appointment.
Data collection
Cancer patients who were referred to a cancer clinical trial research unit and who met the eligibility criteria were sent an information sheet regarding the study before their initial research appointment.
Pre-intervention, 200 patients were screened and then approached to participate in this study; 100 patients agreed to take part. Thirty of the 100 participants were interviewed and all 100 completed the GAD-7 questionnaire.
Once pre-intervention data had been collected, all of the hospital sites that referred patients for an early phase trial were given access to the education intervention.
Post-intervention 250 new patients were screened; 100 patients agreed to take part and completed the GAD-7, 30 of whom were also interviewed.
Data analysis
Pre- and post-intervention interview transcripts were analysed and themes were produced through a method of thematic analysis that allowed coding of transcripts and led to the development of themes. NVivo, a qualitative data analysis computer software package, was employed to review data. Both pre- and post-intervention themes were agreed on through an appraisal and discussion of NVivo coding reports between the author and a senior mental health nurse.
GAD-7 scores data were used to examine if the educational intervention reduced anxiety levels in newly referred patients. To this end, an independent t-test was employed to assess whether the two groups of pre- and post-interventional participants were statistically different from each other, based on GAD-7 scores.
Themes and GAD-7 data were combined to gain an insight into the patient experience pre- and post-intervention.
Results
The independent t-test highlighted that there was a significant difference in mean GAD-7 scores between pre- and post-interventional patients (t=9.213, P<0.001), the post-intervention group had considerably lower levels of GAD-7.
Pre-interventional data indicated that 52% of study participants presented with severe anxiety and 26% had moderate anxiety, whereas post-intervention data indicated the figures were 7% and 17% respectively.
Pre-interventional themes
Four major theme were uncovered from pre-interventional interviews.
Theme 1: motivations for taking part in a clinical trial
The theme ‘Motivations for taking part in a clinical trial’ emerged from the patient interviews. There were three reasons why patients decided to take part in a clinical trial. Within this, four subthemes were ‘altruism’, ‘faith in referring doctor’, ‘hope’ and ‘lack of treatment options’ as the main motivations for cancer patients enrolling on a clinical trial.
Theme 2: worried about taking part
‘Situational anxiety’, ‘COVID-19’ and ‘fear’ were the three subthemes the came to light when reviewing the theme of anxiety from patient interviews. ‘Situational anxiety’ referred to being asked to take part in a clinical trial – this seemed to exacerbate the widespread anxiety cancer patients already experienced. ‘COVID-19-related anxiety’ gave an insight into cancer patients' feelings around going into hospital for a clinical trial, when social distancing measures were in place. ‘Fear’ was the third subtheme, which suggested patients were fearful of going into hospital during the pandemic, due to the very real risk of being infected by the COVID-19 virus. One participant said:
‘I couldn't bring my husband with me to any appointments because of COVID, I could have cried when I was told this, my anxiety went through the roof, he is my rock.’
Participant 1
Theme 3: gap in referring centre education
The third theme that emerged from the data focused on the initial discussions patients had with their doctor about being referred for a clinical trial. Within this theme, two of the subthemes indicated there was a gap in educational resource provision. It indicated that there were no educational resources available to newly referred patients that explained what the patient journey may entail within a clinical trial, either from the hospital or online.
‘I didn't get anything written, I looked at websites but that was my own search, no web address[es] were given to me.’
Participant 123
Theme 4: minimal comprehension of clinical research
A prevalent theme highlighted in the pre-interventional transcripts demonstrated that patients commonly described having minimal or no understanding or knowledge around the concept of a clinical trial. In the pre-interventional interviews patients were asked whether they understood what a clinical trial was, prior to being referred for one. Responses to these questions were brief, but clearly indicated limited or no comprehension at this stage of the referral pathway to clinical trial.
A typical response to questions around pre-referral clinical knowledge was:
‘No, not really, I really wasn't aware of them because I didn't have to be.’
Participant 118
Post-interventional themes
Four major theme were additionally discovered from post-interventional interviews.
Theme 1: motivations for taking part in a clinical trial
An overarching theme that was discovered within post-intervention interview transcripts was ‘motivations for taking part in a clinical trial’. Although the theme's title is the same one that emerged during the pre-data analysis, the subthemes paint a slightly different picture of patients' motivations.
‘Lack of treatment options’ and ‘hope’ were prominent subthemes that reflected the highly emotive decision-making processes that had been taken by patients to participate in an early phase clinical trial. Taking part was seen by patients as a last opportunity to get access to a potential anti-cancer treatment. In most cases they had been told by their doctor that their current treatments had stopped working and this was the only option left to them.
Theme 2: anxiety
‘Anxiety’ was a highly prevalent theme that was broken down into two related subthemes. The first of these was ‘cancer-related anxiety’; this subtheme illustrated the impact of disease burden among these patients. It shed light on the adverse long-term psychological impact of advanced cancer, in essence revealing how a physical disease had increased patients' anxiety.
‘I have had every treatment going, I have been very anxious as I've had this horrible cancer for a long time… it's always at the back of my head, I cannot lie… I'm sometimes an emotional mess with it all.’
Participant 247
‘Waiting time to take part’ was the final anxiety-related subtheme identified. This referred to the period of time it had taken for patients to be seen at their initial research outpatients appointment from being referred. The subtheme indicated that they felt their anxiety levels were increased due to what they perceived as long waiting times for their first research appointment.
‘I was very concerned about the long wait I had, because my last chemotherapy treatment had been in December and it was March by the time I got an appointment here. I thought it's a long time to have no treatment.’
Participant 232
Theme 3: impact of educational intervention
The final theme discovered within data analysis related to the educational intervention. Four subthemes relating to this theme gave an insight into the impact of the intervention.
Patients who had accessed the educational booklet and website acknowledged that this had supported their educational needs. The ‘good level of information given during initial referral’ subtheme suggested that the educational booklet had supported patients' initial consultation about potentially being referred for an early phase clinical trial. This confirmed that the booklet was being given to patients by doctors as a resource to review while discussions about a potential referral were taking place. Doctors also provided links to the website. As a result of this, patients reviewed both the booklet and the website before their first research appointment.
‘Yes, I think the discussion with my doctor about taking part was good, there was no other option other than taking part for me. Thinking back now, he didn't tell us everything we needed to know, but the booklet and website filled in the gaps for us.’
Participant 231
The subtheme ‘new knowledge’ indicated that patients had developed a good level of understanding around aspects of taking part in a clinical trial that were important to them. ‘New knowledge’ focused mainly on what the first research appointment would entail, and gaining an insight into the nature of a clinical trial journey.
‘It set the scene, it gave me a basic idea of what would happen.’
Participant 229
It was particularly noted within this subtheme that patients felt knowing where to go, who they would see and what the stages of taking part in a trial would be, were viewed as key information.
‘It told us exactly what we wanted to know in terms of where the unit was and what would happen when we went to the appointments.’
Participant 234
Intertwined with ‘new knowledge’ was the third subtheme ‘Impact of new knowledge’. Patients said that they had gained an understanding of relevant referral information through using the educational intervention. Analysis of interview transcripts indicated the impact of new knowledge that had been gained from using the intervention:
‘It put me and my wife's minds at ease about what might help there was if I took part in trial.’
Participant 231
‘I think if I hadn't have read that I would have been in a bad place, as it prepared me for disappointment, even though it didn't come to that.’
Participant 235
The final subtheme identified that many patients were giving friends and family the booklet and link to the website to aid their understanding of early phase research. The ‘friends and family resource’ subtheme indicated that patients felt the website in particular was an effective way of allowing loved ones to gain an understanding around the journey they were about to go on.
‘I didn't look at the videos on the website, not for me, but the wife did, my kids did too, well, they watched the videos more than what I did.’
Participant 231
This subtheme revealed that patients felt access to the website removed the pressure of having to explain everything to friends and family, and instead were able to given them easy access to the intervention.
‘There were some good videos on the website, I sent the website link to the daughter to watch them, as I didn't want to have to explain everything and, yeah, she got a better understanding of what [it] might [mean] to me if I decide to take part.’
Participant 253
Theme 4: varied comprehension of clinical research
When reviewing patients' understanding of a clinical trial, before their referral to an appointment to discuss the possibility of enrolling on one, there were varying levels of comprehension among patients.
Similar to theme 4 within pre-interventional interviews, some patients had no previously clinical trial level of understanding:
‘Never been mentioned before. So it was only once they realised that the treatment that I'd been given for the last three and a half years weren't working that I was told I must go somewhere for a trial treatment that I was aware of what they were.’
Participant 248
It was noted that patients who felt they had a level of understanding of clinical trials had gained their knowledge through discussions with friends and family members:
‘Because a friend of mine had many years ago been on a trial, yes I knew. Well I thought I did, until I came here and talked to the doctors, early phase is very different from what she told me about the trial she'd been on. She had been on a trial for her stomach, and told me all about being a patient on a trial, all the appointments and long days.’
Participant 223
A frequent finding in the data was that patients felt they had developed a level of knowledge around what clinical trials were as a result of the COVID-19 pandemic:
‘Yes, I had heard about the vaccines they were making because of the pandemic, it was all over the news of how trials were going to get us through the pandemic. I heard these trials were first in humans.’
Participant 237
In some cases perceived clinical trial knowledge was linked to an awareness of Cancer Research UK, the charity that funds cancer clinical trials. There were varying levels of perceived understanding among this set of patients; however, many patients were mistaken in their understanding.
Pre-interventional themes related to patients' motivations for taking part in a clinical trial, their concerns about taking part and the level of information they were given during the initial stages of being referred for an early phase clinical trial.
Likewise, post-interventional themes encompassed patient motivations, depicting less patient anxiety and additionally presented the impact of the educational intervention.
Discussion
In summarising pre-interventional patients' experiences, the data indicated that the majority of patients had moderate to severe anxiety as a consequence of being offered an early phase clinical trial and as a consequence of the COVID-19 pandemic. When being referred, patients felt information discussed was either too complex or minimal and there were no educational resources given within the referral process. For the individuals in this phase of the study, taking part in an early phase was, in some cases, seen as an altruistic action, or an action guided by faith in their referring doctors with the hope of getting access to a life extending anti-cancer treatment.
On average, post-interventional patients exhibited minimal or mild anxiety levels; however, a proportion of these patients experienced moderate to severe levels of anxiety. The data suggest that anxiety within this group was potentially linked to cancer-related anxiety, and as a result of longer healthcare appointment waiting times. Participants believed that being offered a place in this type of clinical trial was mainly because of a lack of treatment options. Trials were seen as ‘hope’ – as a means to get access to further treatments.
Positive themes around the educational intervention give an insight into the possible reasons why this group of participants exhibited significantly reduced levels of anxiety on the GAD-7 scale, when compared with the pre-interventional group. Intervention-related subthemes such as ‘good level of information given during initial referral’, ‘impact of new knowledge’ and ‘friend and family resource’ indicated positive associations with the initial referral discussions, and with the level and quality of information provided. This was in stark contrast to the pre-interventional participants who highlighted a ‘gap in referring centre education’ and exhibited statistically higher GAD-7 scores when compared with the post-interventional group.
Quantitative and qualitative data indicated that the pre-interventional group had high levels of anxiety, measured on the GAD-7 score and in the interviews, which could be attributed to fear of the COVID-19 pandemic, lack of knowledge around what early phase clinical trials involve and situational anxiety – being asked to consider taking part in such a clinical trial after current anticancer treatments had stopped working.
Post-interventional patients had statistically lower GAD-7 scores than the pre-interventional group. Although anxiety-related themes were identified within this phase of the study, they related to disease burden and the waiting time to take part in an early phase clinical trial.
The post-interventional patients felt the educational resources had given them a good level of information during initial referral discussions with their doctor, which in turn had developed an understanding of what the trials were.
Limitations
The COVID-19 pandemic adversely impacted upon the original research design and implementation strategy.
Conclusion
The quantitative and qualitative data, which were reviewed separately, then considered together, provide an insight into the cancer patient's journey into early phase oncology clinical trials. It offers an insight into the impact of the educational intervention and presents an understanding of why anxiety levels between the pre- and post-interventional groups were significantly different.
In terms of educational impact, post-interventional patients felt they had received a good level of information during initial referral discussions and it had allowed them to understand the potential journey that an early phase cancer clinical trial would involve.
This research study suggests that there are barriers to the decision-making process within the initial stages of the early phase clinical research referral pathway and additionally highlights how educational resources can bridge an educational gap, and reduce such barriers.
KEY POINTS
- The experiences of advanced cancer patients who attended an initial research outpatient appointment to discuss the possibility of taking part in an early phase clinical trial were explored in this study
- The study investigated the impact, if any, of a patient co-designed educational resource for such patients
- The study gives an insight into cancer patients' journey into early phase oncology clinical trials during the COVID-19 pandemic
- This research illustrates the challenges that cancer patients face when considering whether to take part in an early phase clinical trial
- The study also highlights how educational resources can bridge an educational gap, and potentially improve the cancer patient's journey into clinical trials
CPD reflective questions
- Is the amount and quality of clinical research information provided within the NHS good enough to allow patients to understand the basic concepts of what it is like to be a patient within a clinical trial?
- Do you think patient information within your area of work is adequate? If not, what impact do you think this has on your patients?
- If you were asked to explain to one of your patients what taking part in a clinical trial may entail, would you be confident to do so?