Abstract
BACKGROUND:
Breast cancer is the most common cancer in women in Poland and worldwide. Due to growing morbidity and mortality, patients are looking for new therapeutic options. Clinical trials give cancer patients a chance to access innovative treatment often not available in the national healthcare system. Patient awareness of clinical trials is an essential element for the development of the clinical trials market.
OBJECTIVE:
The purpose of this survey was to obtain information from breast cancer patients about their knowledge of clinical trials.
METHODS:
One hundred people were invited to take part in the study, and were recruited into two groups: 50 patients diagnosed with breast cancer less than 40 years of age, and 50 patients with the same disease over 40 years of age. The survey was completed by female patients online.
RESULTS:
Most of the subjects correctly understood the assumptions of the clinical trial; most often, both groups of subjects obtained information about medical experiments from the Internet. According to the respondents, the most important motivating factor to participate in the clinical trial was the proposed study drug and their current state of health. Patients would more frequently decide to participate in a clinical trial at the time of cancer progression compared to immediately after diagnosis. Commuting to the research center made recruitment of older patients more difficult (40% of older patients versus 16% of younger patients, p = 0.008).
CONCLUSION:
Patients with breast cancer are aware of clinical trials and decide to participate in them based on the proposed study drug and their current state of health. Progression of the disease is a factor that increases the willingness to participate in clinical trials.
Introduction
Breast cancer is the most common cancer in women in Poland and worldwide [1]. Due to growing morbidity and mortality, patients are looking for new therapeutic options. Clinical trials test – among others – new, potentially active drugs and their introduction into clinical practice. Participation in a medical experiment therefore gives patients a chance for non-standard treatment under strict supervision, with a regime of performing predetermined procedures and check-ups.
Clinical experience shows that in everyday practice, there is often a lack of time to inform patients about clinical trials in which they could potentially participate, the rules applicable to participants, and the drug route from first experiments to registration. With increased access to knowledge, patient and family determination means that some patients actively search for alternative or additional treatment methods. Sometimes clinical trials are treated as a last resort after traditional possibilities have been exhausted.
Objective
The aim of our survey was to obtain information from breast cancer patients about their knowledge of medical experiments. The following analysis can be a new source of information for physicians, as well as all personnel involved in conducting clinical trials. The presented results should motivate us to carefully provide reliable information about clinical trials throughout the duration of the patients’ therapeutic process.
Material and methods
An anonymous survey entitled “Awareness of breast cancer patients about clinical trials as available treatments” consisting of 35 questions (6 on demographic data and 29 on the main part of the survey) was made available in an electronic form between Feb 02, 2020 and Mar 03, 2020. Popular social media (Facebook) was used and made available to representatives of breast cancer organizations that distributed the questionnaire to their patients. The questionnaire for patients was made available in Polish.
Inclusion of patients
The study was conducted simultaneously in two groups: 50 patients with a diagnosis of breast cancer aged less than 40 years, and 50 patients with the same disease, over 40 years old. After obtaining the required number of people in both groups, the survey was completed. The only criterion for inclusion in the survey was the diagnosis of breast cancer. Participation in a clinical trial in the past did not disqualify from participation in the survey.
Ethics
Information for a potential participant in the survey was placed on the first page of the online survey. It contained information that the survey does not involve any medical intervention and does not affect the assessed health status. The study was conducted after obtaining a full report for the patient about standard treatment and the possibility of using experimental methods. Institutional review board at Poznan University of Medical Science, Bukowska 70 Str, 60-812 Poznan, Poland, does not require to delay anonymous surveys for ethical evaluation. As recommended by the IRB, the authors did not need a commission evaluation for the survey. Patients were informed about anonymous data collection and their use for scientific purposes. Patients were informed that the research did not involve any medical intervention and had no effect on current treatment. Each of the participants in the study gave verbal consent. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Statistical analysis
Statistica 13.3 was used for the analysis. The value of significance was set at 0.05. To compare the percentage results with each other, a z-test was used.
Results
Demographic data
Most of the patients came from villages and towns numbering up to 50,000 inhabitants; in the younger group, 70%; and in the older group, 56%. Residents of cities with more than 250,000 inhabitants constituted 22% of the younger group, and 28% of the older group (Table 1, Q1). About 90% of respondents from both groups had at least secondary school education; 56% of younger women and 32% of older women held university degrees (p = 0.015, Table 1, Q3).
Demographic data
Demographic data
Professionally active people were the largest group in both studied populations: 66% among younger patients and 48% among older patients. In the older group, 38% of respondents were retired (Table 1, Q2). Eighty percent of young patients received a diagnosis of breast cancer in the last two years, and in the older group, 46%. Among older patients, far more were diagnosed over five years ago than in the younger group, (38% versus 6%, p = 0.00012, Table 1, Q5). Tumor advancement was similar in both groups: patients with early and locally advanced breast cancer (stage I–III) accounted for 78% in the younger group versus 80% in the older group, and patients with metastatic breast cancer constituted 8% and 6%, respectively (Table 1, Q6).
From analyzing survey data, it can be seen that patients from both groups learned about clinical trials most often from the Internet (57% of younger women versus 39% of older women, p = 0.11, Table 2, Q2), while some heard from friends who had taken part in the past (in the younger group - 36%; in the older group - 9%, p = 0.042, Table 2, Q3). Most of the patients correctly understood the assumption of the clinical trial and replied that it was testing a new drug; the correct answer was more often given by younger women, compared with older women (72% versus 48% respectively, p = 0.014, Table 2, Q4).
The knowledge of clinical trials
The knowledge of clinical trials
Most problematic for the patients were questions about the number of clinical oncology trials in Poland, the phases of research and the cost of placing the drug on the market, and most chose the answer “I do not know” (Table 2, Q5-8). The concepts of “screening” and “randomization” were also not properly understood, (38% versus 24% and 36% versus 20%, p = 0.041, Table 3, Q3-4) while the term “placebo” and “blindness” were interpreted well by most (86% versus 76%, and 64% versus 52%, Table 3, Q1-2).
The essence of clinical trials
One of the most critical parts of the survey was questions about the motivation to take part in a clinical trial for different study models and the procedures performed at the center. Reimbursement of travel expenses for both groups was not a deciding factor for participation in the study, but it helped towards making a favorable decision (in the younger group - 76%; in the older group - 72%, p = 0.64, Table 3, Q5). Additional procedures require the patient to visit the hospital more often, which may be some distance from their place of residence. As expected, commuting would be more problematic for older patients - 40%, than for younger patients - 16% (p = 0.007, Table 3, Q10).
The most important factors for patients were their current state of health, and the study drug, with both of these factors prevailing over shortening the waiting time for imaging tests. In the case of an attractive drug and good health, patients would risk taking part in a medical experiment regardless of the possibility of additional side effects, or a 50% chance of drawing a medicine or a placebo, or even the possibility of blinding information about the test substance. As we expected, the desire to participate in a medical experiment increases with the advancement of cancer. Twice as many women, regardless of age, thought they would benefit from treatment as part of a clinical trial after disease progression as opposed to immediately after the diagnosis of cancer (63 versus 32%, Table 4, Q5-6). Without a doubt, more young women declared having used IT tool to search for a medical experiment appropriate for a particular clinical situation (98% versus 78%, p = 0.021, Table 4, Q8). Both study groups agreed that the physician should provide information on clinical trials during the consultation, placed as announcements in each oncological hospital. The possibility of using information published on the Polish-language website with a database of clinical trials was of greater interest in 94% of younger patients, than older patients (94% versus 74%, p = 0.004, Table 4, Q3).
The decision to participate in a clinical trial and ethical aspects
The decision to participate in a clinical trial and ethical aspects
The number of applications to conduct a clinical trial in Poland is constantly growing; in 2019, this numbered 514 applications, including 27% related to oncology [2]. The results of the survey indicate that the majority of both groups had heard of clinical trials conducted in Poland, which means there is a high awareness of breast cancer patients about oncological studies of pharmaceutical products. A telephone interview conducted by Gean et al. on a group of 64 American cancer patients indicates that as many as 84% of them were aware of clinical trials [3], reflecting our results on Polish patients with breast cancer.
In recent years, the development of the clinical trials market in Poland has been noticeable. In both study groups, the percentage of breast cancer patients taking part in a clinical trial was just under 10%. In the United States, approximately 20% of patients qualified for oncological clinical trials, and the participation rate was 3–5% [4].
Questions concerning knowledge about the number of phases and research in the field of oncology, or the costs of placing a drug on the pharmaceutical market can be described as expert knowledge. Thus the correct rate of 18% was not unexpected, which means that less than one fifth respondents were able to indicate the correct range of the number of clinical trials in the field of oncology in Poland and correctly marked the total number of clinical trial phases. In 2019, the average cost of the entire laboratory, preclinical, and clinical phases of the pharmaceutical product was 2.6 billion USD [5]. In its entirety, research on the active substance lasted about 12 years [6]. As many as 40% of respondents in the younger group and 58% of the older group, did not know how much the drug development costs from first experiments to drug registration, and 38% of younger patients and 26% of older patients, did not know how long the whole process took, which means that a large part of the surveyed patients, regardless of age, did not have detailed knowledge about the course and costs of clinical trials.
Questions regarding placebo, blindness, randomization, and screening in a clinical trial are key terms that a patient wishing to participate in a pharmaceutical product study should know. As expected, the group of young patients was more familiar with these terms. A survey conducted by Lim et al. on 397 oncological patients at the University Hospital in Seoul indicated that the patient’s level of awareness about clinical trials was associated with appropriate perception and willingness to participate in the study. Although general awareness of clinical trials was high, a relatively large proportion of patients did not have accurate knowledge; therefore, adequate and proper patient education is needed [7]. Based on the results of Polish breast cancer patients, it is possible to conclude that, similarly to the study conducted by Lim et al., appropriate education about clinical trials is needed, especially in older patients.
A patient participating in a clinical trial is more often required to visit the hospital and perform additional procedures, e.g., blood donations, than during standard therapy. Adverse drug-related events may also be more frequent than with an already marketed drug. Both groups of respondents decided to participate in the study depending on their current state of health, and not on the possibility of adverse events. More frequent visits to the hospital were a bigger problem for older patients. The decision of each patient to participate in a clinical trial is a stressful moment, which is why the process of making informed consent is so important. A meta-analysis on the process of signing the informed consent form by Nishimura et al. included 54 randomized clinical trials. Her team found that extended consent forms and longer discussions are most valuable in improving participants’ understanding of the informed consent process [8].
Clinical trials with a placebo or the study drug added to standard therapy are a common model for clinical trial designs. Both groups of patients, assuming that they do not know throughout the entire study period whether they are receiving the study drug or a placebo, most often would make the choice to participate dependent on their state of health at the time of the decision. Placebo oncology clinical trials are scientifically feasible, ethically justified, and may be necessary or desirable to meet regulatory standards for drug approval [9].
In our survey, patients were asked if they would take part in a clinical trial at the time of diagnosis of cancer or at the time of progression. There were no significant differences between the study groups in response. Over 30% said they would decide to participate in a clinical trial at the time of diagnosis, and over 60% only at the time of disease progression. As expected, the search for new treatment options increases with the advancement of cancer.
Demographic and socioeconomic differences during selection for examination may occur anywhere on the road from the first visit to the clinic until the patient finally decides the treatment. The most consistent and most significant difference concerns age [10,11]. A survey conducted by Lemieux et al. in Canadian breast cancer oncology centers and patient organizations to identify barriers to recruitment for clinical trials with breast cancer and protocol characteristics indicated that the recruitment fraction varies from 5.4 to 8.5%. The main problems related to patient recruitment are: lack of available clinical trial, patient’s misunderstanding of the essence of placebo and too long waiting time after surgery for inclusion in the study [12]. In the conducted survey, the percentage of Polish breast cancer patients participating in a clinical trial in the past was about 10% in both age groups. However, the authors did not verify whether the patient actually participated in the clinical trial. Patients with breast cancer in both groups agreed that the oncologist should inform them about possible clinical trials at each stage of treatment. Young patients were more likely to use IT tools that could potentially analyze inclusion criteria.
Only 26% in both study groups asked the physician for possible clinical trials at the time of the diagnosis, and more than 70% thought about taking part in a future clinical trial. Telephone interviews by Avis et al., with 208 patients with breast cancer, suggested that reducing commuting problems in reaching the center and improving communication between physicians to undertake recruitment activities are necessary to increase patient participation in clinical trial studies [13]. Long travel time to research centers, which are often tens of kilometers away from patients’ homes, is a factor negatively influencing the decision to participate in the clinical trial. As a consequence, this may primarily affect older patients, who often require assistance in reaching the trial site.
Conclusion
Patients in Poland with breast cancer are aware of clinical trials, and most of them understand the assumptions of oncological research in pharmaceutical products. The most important motivating factor in participation in the study for both groups is the proposed study drug and their current state of health. In case of these two factors, both groups of respondents will risk participating in a clinical trial, regardless of the study model or the possibly higher frequency of adverse events. Patients, regardless of age, would more often decide to participate in a clinical trial at the time of cancer progression rather than at the time of cancer diagnosis. The additional procedures required by a clinical trial protocol involve more frequent hospital visits, which makes recruitment of older patients more difficult. Both groups of respondents agree that information on clinical trials should be available in every oncology hospital, and that oncologists should inform patients about the possibilities to participate in them during the consultation. Clinical trials are an essential element in the development of medicine, and for cancer patients, they are above all a chance to access an innovative drug often unavailable in the national oncological treatment system.
Footnotes
Acknowledgements
The authors thank Jadzia Tin-Tsen Chou for her help on language revision.