healthmedicinet

The majority of patients in our survey were happy to be approached about participating
in cancer research and were keen to participate in clinical trials. We chose to develop
our own survey as existing surveys, such as the UK National Cancer Experience Survey,
cover a broad range of topics and only include a few questions on clinical trials.
Although our survey was less well-validated, it allowed us to determine the proportion
of patients who consented to a clinical trial as well as investigate patients’ views
on cancer research in more detail. Reassuringly, our results were consistent with
the UK National Cancer Experience Survey, which reported that 95 % of patients who
had research discussed with them were happy to have been asked and 53 % of patients
with whom research was not discussed would have been happy to have been asked 17]. However, patients who have just started their first treatment for cancer are less
likely to participate in cancer research and it appears that as time increases from
diagnosis, patients are more positive about engaging with research 6], 18]. This may reflect the availability of clinical trials, but may also be influenced
by factors such as the psychological impact of a recent cancer diagnosis. Patients
were particularly willing to consent to non-CTIMP trials, possibly due to the less
interventional nature of these studies. We had originally planned to compare the characteristics
of the patients who consented to a trial with those who declined a trial, but this
was not possible due to the small number of patients who declined a trial.

However, although a high proportion of patients consented to a trial, 36 % of patients
subsequently failed screening for CTIMP/pre-screening trials. Screen failures may
become increasingly problematic due to the growing number of biomarker selected/stratified
trials. Twenty-eight percent of our trial portfolio involved tissue analysis prior
to patient randomisation (either to determine eligibility or for stratification),
resulting in 66 % of screen failures being caused by patients’ molecular profiles
or a lack of tissue for analysis. This has important logistical and workload implications,
as staff time is required for trial set-up, patient recruitment and specimen coordination,
even though many patients are subsequently ineligible for the trial.

In agreement with other studies, we found that patients’ decisions to participate
in research are influenced by multiple factors including altruism, trust in their
treating physician and beliefs that they would receive superior treatment, closer
monitoring and better quality care 11], 12], 19]–23]. However, the ‘most important’ reason varied according to factors such as trial type
and treatment intent. Although 52 % of patients consenting to CTIMP trials were motivated
by a belief that the trial was the best treatment option available, 25 % of patients
participated for altruistic reasons. Interestingly, 15 % of non-CTIMP trial respondents
felt that the trial offered the best treatment available. For some trials (e.g. molecular
profiling trials), this was a logical response. However, other trials had no direct
patient benefit and, therefore, some patients seem to have misunderstood the trials’
aims. Other studies have shown that patients can misunderstand the potential personal
benefit from clinical trials 13], 20] and it is important to ensure that patients clearly understand the purpose of any
trial and any trial-related procedures.

Translational research is increasingly important and patients’ opinions of tissue
and genetic research should be considered by researchers and ethics committees when
assessing translational research protocols. Reassuringly, only 7 % of our patients
had concerns about the use and storage of blood/tissue samples for research, and indeed,
many patients strongly felt that this was not an issue. This is supported by the results
of other studies, which demonstrate that the majority of cancer patients would allow
the use of their tissue for research 13], 24], 25]. In our survey, 78 % of patients would agree to donate tissue for genetic research,
even if they were not told their genetic results, indicating patient support for genomic
research into cancer. However, these results should be interpreted with caution as
no information was provided in our questionnaire regarding the potential implications
of genetic results, so patients’ understanding and knowledge of any potential issues
is unknown.

Biopsies are becoming an increasingly common component of clinical trials and 42 %
of our trials involved an optional or mandatory biopsy. There have been ethical concerns
about mandatory research biopsies: e.g. a lack of alternative treatment options and
patients’ understanding of biopsy risks and the purpose of the biopsy 14], 26]–28]. Although some patients would not participate in trials involving a biopsy, it is
important to highlight that 75 % of our patients stated they would consider participating
in a trial involving a repeat biopsy. This is significant as staff and ethics committee
assumptions regarding patients’ attitudes to biopsies may not be accurate. For example,
a survey of patients, medical oncologists and Institutional Review Board (IRB) members
on the issue of mandatory research biopsies demonstrated that oncologists and IRB
members may over-estimate the anxiety associated with biopsies and that patients would
accept a higher risk of biopsy-related complications than oncologists/IRB members
13]. Furthermore, staff may be reluctant to discuss biopsies with older-aged patients
or patients with a poorer PS due to assumptions that these patients would not wish
to undergo any additional procedures. Interestingly, age and PS did not significantly
impact on the willingness of our patients to consider a biopsy and we feel that these
factors need not be a barrier to discussing biopsies with patients, allowing them
to make their own decisions.

Patients being treated with palliative intent and patients who have received more
lines of treatment appear to be more willing to consider a repeat biopsy. This could
be due to a number of reasons, including willingness to participate in anything that
could potentially benefit them, increasing altruistic motives or a better understanding
of cancer and its treatment. Patients with a recent diagnosis of cancer are often
keen to start treatment as soon as possible, and may be deterred by concerns regarding
potential biopsy-related delays, may feel psychologically overwhelmed by their diagnosis
and, as previously mentioned, are less likely to engage in research 18]. However, these results should be interpreted with caution due to the small number
of patients in the subgroup analyses and because trials in more advanced lines of
treatment were more likely to contain a biopsy component. Further research is needed
into patients’ views on biopsies, particularly as it has been suggested that previous
negative biopsy experiences may discourage patients from future biopsies 29].

Lengthy trial information can be off-putting to patients 22] and healthcare staff may feel that patients are overwhelmed by the amount of information
provided, particularly as they have often also received information about their cancer
and their standard treatment options. In addition, lengthy trial information can lead
to a poor recall of risks and it has been suggested that shorter information leaflets
might lead to better informed consent 30]. Indeed, one patient admitted to not having read the PIS, and this is not unique
to our study 31]. PIS are often reviewed/tested by patients prior to submission to ethics committees,
and this can result in amendments to their wording and layout that make the final
version easier to understand 32]. However, even though the average PIS length was 17 pages, 55 % of patients clearly
stated they did not feel it was too long and 48–50 % of patients approached about
CTIMP studies would have liked more information on the study drugs/procedures. Therefore,
there does seem to be a group of patients who wish to know more details about the
trial, and indeed many of the free-text comments expressed a desire for more detailed
information. The majority of patients discussed the trial with family members, and
so patients’ relatives may also wish to have more detailed trial information.

However, approximately 20–28 % of our patients did not want more information on the
trial drugs/procedures and other studies have shown that patients feel that the amount
of information provided is sufficient 11]. A one-size-fits-all approach is, therefore, unlikely to suit the needs of every
patient, and strategies to tailor information according to the individual patient’s
wishes should be explored. Fifteen percent of patients looked up additional information
(rising to 32 % for CTIMP studies) and, therefore, one strategy could be to provide
a link in the PIS to a website containing further trial information. This would have
the advantage of providing a resource for interested patients without overloading
patients who are satisfied with the level of information already provided.

Patients who enrol quickly into clinical trials may not feel that they fully understand
the implications of trial participation 33] and, therefore, ethics applications may state that patients will be given at least
24 hours to consider the information provided. However, some patients find it inconvenient
to return specifically to sign consent and do not wish to delay screening procedures/treatment.
This can be a particular issue for pre-screening trials, which involve biomarker testing
of archival tissue to identify patients who might be eligible for corresponding CTIMP
trials. As 79 % of patients approached about pre-screening trials would have been
willing to consent on the same day as receiving the PIS, perhaps patients who wish
to consent on the same day should be able to do so (with the important caveat of ensuring
patients do not feel pressurised into signing consent).

Although 75 % of patients in our survey (rising to 89 % for CTIMP trials) felt participants
should be informed of trial results, these are not always effectively communicated
to patients. The question was specifically worded to highlight the fact that results
may not be available for many years, although it did not directly state that patients
may be deceased at the point when final study results are available. Our results are
comparable to those from other studies 22], 34]–36], indicating that the majority of patients feel they should be offered the trial results,
not only for their personal interest and satisfaction, but also out of respect for
their contribution to the trial 22]. One of the concerns regarding the feedback of trial results is the potential for
psychological distress (e.g. due to randomisation to an arm with inferior outcomes)
35], 36]. However, although receiving results can be distressing 37], 38], this does not necessarily lead to regret at receiving results and some patients
suggested that the satisfaction of knowing the results outweighed the potential distress
of hearing bad news 36]. Indeed, one study demonstrated that 84 % of patients would like to receive results
from a negative trial 36] and receiving study results may improve participants’ research experience 39]. Furthermore, not receiving results may deter patients from participating in future
trials 34].

However, the optimal content, timing and method of providing results to participants
is currently unclear, with our patients being divided as to whether results should
be provided in clinic or via a letter. Some patients wish to know their personal results,
others want the overall study results and many wish to know both 36]. In addition, patients are keen to receive regular updates on the trial’s progress
22], 36], 40]. Many sponsors provide participating sites with newsletters providing progress updates,
so one strategy could be to provide a lay version of these newsletters to interested
patients as well as a lay summary when the results are available.

When considering the applicability of our results to other patient populations, there
are a number of factors that should be considered. Firstly, the structure of the UK
health service (which is not dependent on patients’ health insurance) may facilitate
trial participation 41]. Secondly, our patients were predominantly white, middle-class men with low levels
of social deprivation. Although we did not specifically assess the educational level
or health literacy of our patients, it is likely that our patients are more highly
educated than patients from more deprived socioeconomic backgrounds, and issues such
as lack of support, financial worries and difficulties with transport may be less
problematic for our patients in comparison to patients from socially deprived areas
42]. Despite this, it is concerning that 21 % of patients either did not correctly state
their diagnosis or left this question blank. It is uncertain whether the patients
who did not answer the question accidentally missed the question or did not know what
to write. If patients have not accurately understood their diagnosis, then they are
less likely to fully understand the trial information. In addition, this survey only
included patients with GI malignancies or lymphoma, and their views (particularly
on biopsies) may differ from patients with other types of cancer. Also, the trial
portfolio was heterogeneous in nature and the characteristics of the individual trials
(e.g. palliative versus curative, study phase) and PIS may have influenced patients’
responses.

In addition, whether patients’ answers to the questionnaire truly reflect their views
on the PIS is uncertain. Patients’ responses may be influenced by ‘social desirability’:
i.e. they may give a socially desirable response if they know someone else will read
their answers 43]. Furthermore, patients may falsely believe they have understood the PIS. For example,
93 % of patients in one phase I study stated they understood most or all of the information
provided, but only 33 % were able to state the purpose of the trial in which they
were participating 12]. Additionally, some of the questions were hypothetical in nature for some patients,
as they were not relevant to the type of trial for which they had received a PIS and
this may have influenced their responses.

However, it is important to highlight that although RM is a specialist cancer centre
and patients referred from elsewhere in the UK for consideration of clinical trials
may be more motivated to participate in cancer research, the majority of patients
in our survey lived locally and were not referred to RM specifically for a trial.
In addition, one of the main strengths of this survey is that a high proportion of
patients who consented to a trial also completed the questionnaire (thereby minimising
any potential bias between questionnaire responders and non-responders).