One in two New Zealanders will have contact with cancer, either personally or through a relative or friend.1 Cancer remains the leading cause of mortality in New Zealand and is likely to be the defining health issue for the next decade.2 Clinical trials are designed to improve patient outcomes with the ultimate global priority being to reduce cancer-related morbidity and mortality.3 They are integral to the advancement of patient care and central to regulatory approvals and patients participate in clinical trials to access new drugs/regimens and to improve science and to help others.

Survival rates for paediatric cancer patients have quadrupled over the past four decades, driven by the introduction of new therapies coupled with the high rate of clinician and patient involvement in clinical research.4,5 Over 60% of children with cancer in the US are enrolled in clinical trials, compared to fewer than 5% of adult patients; even lower rates are seen in elderly patients, females and ethnic minorities.4 High rates of trial participation allows for rapid evaluation of new therapies, and delineation of the sub-populations that do benefit, ultimately informing both current practice and future trial design.4

Studies have investigated reasons for low participation and recruitment. It is well recognised that this is a multi-faceted problem with clinician, patient and institutional factors contributing.4,6–9 Key factors identified include a paucity of trials available, cost (financial and time), belief in the study, age and comorbidities.7–9 Based on previous studies, patient-related factors are thought to be a small component of low participation in trials. In most series approximately 20% of patients eligible for a trial do not participate; this is likely to represent both clinician and patient factors.10–14

Understanding the reasons why people do and do not participate on trials will inform strategies to improve recruitment rates. We designed a study to look at factors that influence clinical trial participation for New Zealanders diagnosed with cancer. This included a survey of patients and a survey addressing institutional and clinician barriers to research. Herein, we report the responses to the patient survey. We hypothesised that patients are not the limiting factor for clinical trial participation in New Zealand.

Method

Ethical approval for the patients’ survey was given by the national Health and Disability Ethics Committee. Cancer Trials New Zealand (CTNZ) sponsored this study as part of the University of Auckland.

Study subjects

Patients across New Zealand with a cancer diagnosis were invited to complete a questionnaire from July 2016 to June 2017. Questionnaires were circulated to nine district health boards (DHBs) and advertised by four cancer charities (melanoma, prostate, breast and gastrointestinal cancer) through their websites and newsletters as well as clinics and chemotherapy suites. Survey participation was voluntary and questionnaires were anonymous.

Questionnaires

Patient questionnaires were developed based on literature review and identification of cultural aspects relevant to New Zealanders.15 Input from Māori and patient representatives was sought in developing the questionnaire. The questionnaires were only available in English and comprised 27 multiple choice or Likert scale questions (see Appendix). The questionnaire covered participation in clinical trials, attitudes to participation, factors which might influence participation in trial such as travel and extra investigations, and demographic factors. All answers were self-reported. The questionnaires were completed in clinic or taken home and returned via pre-paid post or completed online. Questionnaires had no patient identifying information.

Statistical analysis

Summary statistics were generated for the descriptive data: counts, percentages and averages. Univariate logistic regression analysis was used to determine associations between patient characteristics and patient responses.

Results

From July 2016–June 2017, 691 cancer patients completed the survey across New Zealand (Table 1). Of the respondents, 62% were female and 77% were over 50 years old. Over 80% of the respondents self-identified as New Zealand European whereas 7%, 3.5% and 2.5% identified as New Zealand Māori, Pacific Islanders or Asians, respectively. About half of the respondents were treated in the Northern Cancer Network, which covers Northland and the greater Auckland region. Most questions had high response rates, apart from household income and cancer site questions, which had missing data rates of 12% and 10%, respectively.

Table 1: Patient demographics.

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The annual household income was below $55,000 (NZD) in 40% of the respondents. This means that 40% of the respondents were either on single income or benefits as average wage in New Zealand was $49,000 in 2016.16 Breast and gastrointestinal (GI) cancers were the two most common cancer types and made up 50% of the survey respondents. More than two thirds of the respondents had surgery and chemotherapy in their cancer journey and 50% of the respondents had had their cancer diagnosis for less than one year (Table 1).

About 80% of the respondents travelled up to one hour to get to their treating centre and more than half of the respondents reliant on others for transport (Figures 1 and 2). Friends and families were more likely to provide transport for Pacific Islanders (81%) compared to New Zealand Europeans (45%) (RR=1.74, p<0.0001) and Asian patients (58%) (RR=1.33, p=0.21).

Figure 1: Travel time to hospital.

Figure 2: Mode of transport.

Are patients interested in clinical trials?

The majority of the respondents had heard of clinical trials or would consider participating in a trial (89% and 86% respectively), but only 23% had a trial mentioned and 18% had prior experience in clinical trials (Figure 3). In terms of timing of clinical trials, 60% wanted a clinical trial to be discussed at any time there was a relevant trial for them, with only 10% considering that clinical trials should be reserved as a last option. Asian patients (17%) were more likely to view clinical trials as the last resort compared to New Zealand Europeans (9%), but this was not statistically significant (RR=2.12, p=0.145). Respondents did not mind travelling for a clinical trial, with a third of the respondents willing to travel up to two hours and 11% willing to relocate to access an appropriate clinical trial.

Figure 3: Awareness and prior experience of clinical trials.

New Zealand cancer patients showed high level of interest in considering clinical trials and this was consistent across different age groups, gender, incomes, ethnicities, cancer networks and the duration of cancer diagnosis. The group with a combined household income of less than $55,000 were less likely to consider trials (RR 0.87, p=0.0001) to those with a combined income over $55,000, but there was no statistically significant difference by age group, gender, ethnicity, cancer network and the duration of cancer diagnosis.

Of the respondents with prior trial experience, 94% would consider joining further trials and only 2.5% said they would definitely not participate in a further study due to factors including their general state of health; only one patient reported treatment-related toxicity as the reason they would not wish to be involved again. Patients with prior clinical trials experience were more likely to be interested in future research compared to patients without trials experience (RR 1.11, p<0.0001).

Which factors influence patients to consider clinical trials?

The main motives for respondents to consider clinical trials were to benefit fellow patients (92%), help doctors’ research (85%) and to access better treatment (82%) (Figure 4). Many regarded extra investigations and longer follow-up as positive aspects of joining clinical trials and only 15% felt this would discourage them from participating in a clinical trial.

Figure 4: Factors described as motivators for clinical trials participation.

Disincentives for trial participation included fear of randomisation (78%), treatment toxicities (71%), time and cost of more visits (40%) and unspecified future use of tissue (32%) (Figure 5). Fear of randomisation was higher in Pacific Islanders (92%) compared to New Zealand Europeans (78%) but this was not statistically significant (RR 1.06, p=0.41). Up to one quarter of New Zealand Māori, Pacific Islander and Asian respondents raised cultural issues related to participating in clinical trials, but this only affected 5% of New Zealand European respondents.

Figure 5: Components of clinical trial participation described as a disincentive for clinical trial participation.

Discussion

Currently there is no accurate estimation of the true number of patients enrolled on a clinical trial, but it is estimated to be only in the order of 1–2%. This is significantly less than international targets but is still a challenge faced globally.14,17 National Cancer Research Network (NCRN), the UK initiative to improve cancer research participation, increased patient recruitment from one in 26 patients to closer to one in six by having 34 dedicated research units throughout the country to support and streamline research activities locally and nationally.18 Cancer trials make up less than 8% of all the registered trials on them Australian New Zealand Clinical trials Registry.19 The INSIGHT project was designed to better understand and to improve New Zealand cancer patients’ participation in clinical trials.

Many factors have been raised as incentives and disincentives in considering clinical trials.7–12 In our survey respondents, additional investigations and longer follow-up did not seem to deter patients from participating in clinical trials, but randomisation was a concern for nearly 80% of the respondents.15,20 This may reflect limited public awareness of the need for clinical equipoise in the design of clinical trials. Patients may be unaware that the standard of care is often the comparison and that the reason for conducting clinical trials is that we do not yet know if the experimental arm is better or worse than current standard of care. This highlights the importance of improved education and information for patients on the objectives and design of clinical trials.

Cultural beliefs are an important consideration in the implementation of trials and may impact on a patient’s willingness to be involved in a trial. Illustrating this, there are strong Māori values and beliefs around the disposal of human tissue and body parts, with traditionally all tissue to be buried where the person would be buried after death. With the increasing requirement for archival tissue as part of eligibility criteria this may impact on participation and access to trials. In our study, the proportion of Māori and Pacific patients who saw research on tissue as a deterrent was higher than for New Zealand European, but this was not statistically significant. This was limited by the number of respondents.

Lower socioeconomic groups are often poorly represented in trials. 21 The cost of trials extends beyond the running of the trial and includes costs to the patient with respect to time and financial implications. Financial toxicity, the burden of ‘out-of-pocket’ expenses, has been recently described as an additional toxicity to therapy.22 Cost concerns are more evident in lower socioeconomic groups, who are often poorly represented in trials.21 In our study, the 40% of patients who reported their annual household income to be less than $55,000 appeared less likely to express an interest in participation compared with those with annual household income above $55,000 (RR 0.87, p=0.0001). It is important to recognise this is limited by our sample size participation rates. While some studies provide some financial and transport support, strategies and support systems to off-set patient costs is not available for all trials, which may influence trial participation from low socioeconomic groups. The indirect costs of cancer care such as transportation, child care and lost wages are often not covered.23 The ramifications of being involved in a clinical trial impacts more than just the patient, and includes the lives of their spouses, families and friends.23

Travel costs and time are important considerations as the distance from a cancer centre is a common contributing factor to non-participation on trials.6,7,14 In our study, over 60% of patients were prepared to travel for a clinical trial and 10% were prepared to relocate, and interest in clinical trials did not differ by potential travel time to hospital. Patients may choose to travel and actively seek trials with the goal of living longer or better, but this means they often leave their key support network. Delivery of clinical trial is often limited to university-affiliated public hospitals with research connections as it requires dedicated research infrastructure and staff to standardise cancer care. Strategies need to be devised to attempt to modify trials so that patients can do some investigations locally to alleviate geographical stress. This is something we should be able to achieve for New Zealanders.

The main strength of the study is the contribution from nearly 700 patient-respondents across New Zealand. However, we acknowledge that the respondents to this survey remain a highly selected cohort and may not represent general cancer patients due to its voluntary nature and English-only questionnaire. This is illustrated by a disproportionate number of respondents from the Northern region and the high percentage of patients with breast cancer.

Of the respondents, 18% had been involved in a clinical trial. This is significantly higher than the anticipated percentage and implies an inherent bias with these patients more likely to have been exposed to a clinical trial than our general patient population. Additionally, because the survey was distributed through multiple modalities to capture a large patient cohort, we cannot appreciate the true denominator to assess response rate. Due to the voluntary nature of the study, it is likely we will have attracted patients with an interest in clinical trials. Similar prospective questionnaire studies in the UK have concentrated on patients being screened for a clinical trial, hence smaller in numbers (358 and 276 respondents).15 In the future we aim to replicate similar research and concentrate on patients where a trial has been offered to better understand the factors facilitating and deterring patients from trials so we can help improve patient engagement.

Another limitation of the study was the English-only questionnaires. This may explain the under-representation from the ethnic groups where English was not the principal language of communication. Many studies have hypothesised that social, language and cultural factors play a role in impacting on communication as well as a possible heightened wariness.4,8,24–26 Despite disparities in ethnic representation in this study, in responders there was a strong level of interest to consider clinical trials (80% in Māori, 71% in Pacific Islander and 66% in Asian patients). This is biased by the sample size and patient population who contributed to this study. In the US it has been demonstrated that while there are ethnic differences in trial participation rates, there are no differences in willingness to participate.27 The fact that more Asian respondents regarded clinical trials as a last resort may be related to education around objectives of clinical trials and trial participation.27–29 This will need to be further explored with a focus group, as this may reflect a need for better education rather than a language barrier.28,30 Again, these issues may be addressed by improved patient information around clinical trials.

At a national level, there is a responsibility to improve access to trials for all New Zealanders with a cancer diagnosis. It is important for all our patients as there is clear evidence that patients treated at cancer institutions with high research involvement have better outcomes.31,32 It is also important to note (in our study) that of those who had been involved in a clinical trial, 94% would like to be involved in future trials, implying that their involvement had been a positive experience. We plan to look into patient experience on trials in more detail in the future.

Conclusion

This study confirms that New Zealand cancer patients have high interest in clinical trials and would like to know more about clinical trial opportunities. Identified patient-related factors could be minimised through ongoing education, equitable access to trials and improved patient awareness of research opportunities.

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