Attitude and perception toward clinical trials in India among patients and patient bystanders visiting the Indian Ophthalmology Clinical Trial Network: A multi-centric, cross-sectional survey
This was a cross-sectional study conducted over multiple locations of India, namely, Chitrakoot (Central), Guwahati (East), Kochi and Trivandrum (South), and Mumbai (West). Five tertiary care hospitals across these locations of India that are a part of IOCTN were chosen as the sites where the survey was performed. Because the study’s geographic scope did not encompass all of India, the data for each area were examined separately to see whether there were any differences between them. The study duration was 3 months for data collection and 1 month for data analysis. The inclusion criteria of the respondents were (i) patients/patient bystanders (patient attendants) visiting the out-patient department of these hospitals for consultation or admittance, (ii) patients above 18 years of age, and (iii) patients who had never participated in any CT prior to and during the survey period of the study. The exclusion criteria included patients and bystanders who were blind, those who were unable to comprehend the questionnaire, and those who expressed their unwillingness to participate in the survey. The survey comprised a multiple-choice questionnaire developed from a previously validated questionnaire by a team of researchers and doctors. The survey questionnaire was developed in English language and translated to site-specific regional languages. Prior to data collection, the questionnaire was approved by the institution’s ethical committee, and participants were required to fill a written informed consent before answering the questions. Sample size The statistically viable sample size was determined to obtain a 95% confidence interval of 10% or less for a binary outcome using the maximum variance assumption (0.25) and a design effect of 1.5 to account for the sampling error. Each center required a minimum sample size of 150 for a total of 750. Individuals who visited these hospitals during the study period as either patients or bystanders (patients’ companions) and who had never participated in any CT served as the study’s sampling units. Statistical analysis Two sections of the questionnaire were used to evaluate the respondents’ views toward CTs and their level of expertise. Those who were unfamiliar with the phrase “clinical trial” were given a brief explanation of what it is before being asked a series of questions to gauge their opinions about CTs. To determine whether a priori knowledge of the CT affects attitudes, the two groups’ replies were examined individually. The study performed both univariate and multivariate analyses to pinpoint the socio-demographic factors that may influence the knowledge and attitudes of the respondents, besides their location.   The statistically viable sample size was determined to obtain a 95% confidence interval of 10% or less for a binary outcome using the maximum variance assumption (0.25) and a design effect of 1.5 to account for the sampling error. Each center required a minimum sample size of 150 for a total of 750. Individuals who visited these hospitals during the study period as either patients or bystanders (patients’ companions) and who had never participated in any CT served as the study’s sampling units.   Two sections of the questionnaire were used to evaluate the respondents’ views toward CTs and their level of expertise. Those who were unfamiliar with the phrase “clinical trial” were given a brief explanation of what it is before being asked a series of questions to gauge their opinions about CTs. To determine whether a priori knowledge of the CT affects attitudes, the two groups’ replies were examined individually. The study performed both univariate and multivariate analyses to pinpoint the socio-demographic factors that may influence the knowledge and attitudes of the respondents, besides their location.   The minimum required sample size of 150 respondents from each location was achieved . The ratio of male to female in the total sample was 55:45, and the average age was 48 + 15 years. Chitrakoot had the greatest male to female ratio, while Kochi had the lowest. 42% of the sample belonged to urban areas, 19% from semi-urban areas, and 38% from the rural areas. Chitrakoot and Mumbai had the largest and lowest percentages of responders belonging to rural areas, respectively. Only 2% of respondents were illiterate. TVM had the lowest rate of illiteracy, while Chitrakoot had the highest. 20% of the respondents worked in the private sector, while 7% had government job. 13% of respondents had their own business, and 10% were had retired from service. 20% of people were engaged in other jobs, while 30% were unemployed. The highest proportion of unemployed respondents belonged from TVM, while Guwahati had the lowest proportion of unemployed respondents. Five sub-samples differed significantly from each other regarding their socio-demographic profile ( P value < 0.001, ). Knowledge and perceptions about clinical trials among those who were already aware about CTs 42% (533 of 1260) of the respondents were aware of CT. The denominator for the percentages mentioned in this section was the number of those who had a priori knowledge about CTs (i.e. 533). No responses were treated as missing values. The primary source of awareness about CTs was the social media platform (53%), followed by doctors they met in the hospital set-up (38%). 7% had heard it from their friends and relatives. 54% of the respondents thought that animals were the test subjects of CTs; 16% believed it involved humans only, and 25% knew that both humans and animals can take part in CT. 64% of the respondents knew CT is conducted to develop new drugs or new treatment procedures. 60% considered CTs as risky affairs where human participants are treated like guineapigs. 64% thought participants in CTs receive better care and attention at the hospitals, and 81% were under the impression that CTs are supervised by the government. 47% knew participation in CT is voluntary, and 47% would expect benefits such as free treatment, medical insurance, travel allowance, etc., if they participate in CTs. 89% believed that participating in CTs would benefit the society. 87% of the participants emphasized on the trust and confidentiality of those participating in CTs, and 72% confirmed seeking permission from relatives is essential to participate in CTs. Responses to almost all questions explained above significantly varied across locations. Some also varied according to gender, level of education, age, type of respondents (patients or bystanders), and place of locations (urban, semi-urban, and rural). summarizes the level of significance for the difference in response levels for each question according to different factors from a univariate analysis. Therefore, the difference in perception between the two groups with and without a priori knowledge about CTs was analyzed  Difference in perceptions between the two groups with and without a priori knowledge about CTs Five perception-based questions – on usefulness of CT – about time consumed by CTs, benefits received by the participants, need for awareness about CTs, and individual willingness to participate in CTs were asked to all respondents irrespective of their a priori knowledge about CTs. Those who were not aware of the abovementioned aspects about CTs were made aware before the questions were asked. Overall, 90% of the respondents had the opinion that CTs are useful for the medical progress, and hence, it is ultimately useful for the society. The proportion significantly varies across locations ( P value < 0.001) but does not significantly change between the two groups of participants – with and without a priori knowledge of CTs ( P value = 0.474). 47% of the respondents perceived CTs are time-consuming. This proportion, too, significantly differs across locations ( P value < 0.001) but not between the two groups ( P value = 0.282) with and without the prior knowledge. 71% felt that CTs are beneficial for the participating patients, and the proportion is significantly different between the locations ( P value < 0.001). The two groups also recorded significantly different proportions in favor of the issue. It was 83% among those with a priori knowledge against 67% among those without any a priori knowledge ( P value < 0.001). 8% of those who were not previously aware assumed that CTs may be harmful for the patients, whereas the proportion was less than 1% in the other group of respondents ( P value < 0.001). 79% of all respondents – 93% in the group with previous awareness and 73% in the group with no previous awareness – suggested creating more awareness about CTs among the patients. The difference was significant across locations ( P value < 0.001) as well as between groups ( P value < 0.000). 48% of the sample expressed their willingness to participate in CTs. This included 30% of those who were previously aware and 55% of those who were not, and the proportions significantly vary across locations and between groups. Multivariate analysis Multivariate logistic regression analysis was applied with five perception-based questions as outcome variables and socio-demographic factors and locations as covariates. The results of the multivariate logistic regressions are summarized in . All the factors analyzed—gender, age, education, occupation, and place of residence—have an impact on some outcomes. Education was the most ubiquitous component. With the exception of willingness to engage in CTs, a higher education was found to be positively associated with favorable attitudes of CTs. Although they are more likely to see the societal advantages of CTs, people with greater education are also less inclined to take part in them. People with higher levels of education are more likely to understand that CTs take time. People in semi-urban or metropolitan settings are also more likely to be aware of the time taken for CTs than people in rural areas. The occupation is another universal component. Government employees were reported to have favorable opinions about CTs and to be eager to take part in them. Regardless of their socio-demographic standing, perceptions vary between areas.   42% (533 of 1260) of the respondents were aware of CT. The denominator for the percentages mentioned in this section was the number of those who had a priori knowledge about CTs (i.e. 533). No responses were treated as missing values. The primary source of awareness about CTs was the social media platform (53%), followed by doctors they met in the hospital set-up (38%). 7% had heard it from their friends and relatives. 54% of the respondents thought that animals were the test subjects of CTs; 16% believed it involved humans only, and 25% knew that both humans and animals can take part in CT. 64% of the respondents knew CT is conducted to develop new drugs or new treatment procedures. 60% considered CTs as risky affairs where human participants are treated like guineapigs. 64% thought participants in CTs receive better care and attention at the hospitals, and 81% were under the impression that CTs are supervised by the government. 47% knew participation in CT is voluntary, and 47% would expect benefits such as free treatment, medical insurance, travel allowance, etc., if they participate in CTs. 89% believed that participating in CTs would benefit the society. 87% of the participants emphasized on the trust and confidentiality of those participating in CTs, and 72% confirmed seeking permission from relatives is essential to participate in CTs. Responses to almost all questions explained above significantly varied across locations. Some also varied according to gender, level of education, age, type of respondents (patients or bystanders), and place of locations (urban, semi-urban, and rural). summarizes the level of significance for the difference in response levels for each question according to different factors from a univariate analysis. Therefore, the difference in perception between the two groups with and without a priori knowledge about CTs was analyzed    Five perception-based questions – on usefulness of CT – about time consumed by CTs, benefits received by the participants, need for awareness about CTs, and individual willingness to participate in CTs were asked to all respondents irrespective of their a priori knowledge about CTs. Those who were not aware of the abovementioned aspects about CTs were made aware before the questions were asked. Overall, 90% of the respondents had the opinion that CTs are useful for the medical progress, and hence, it is ultimately useful for the society. The proportion significantly varies across locations ( P value < 0.001) but does not significantly change between the two groups of participants – with and without a priori knowledge of CTs ( P value = 0.474). 47% of the respondents perceived CTs are time-consuming. This proportion, too, significantly differs across locations ( P value < 0.001) but not between the two groups ( P value = 0.282) with and without the prior knowledge. 71% felt that CTs are beneficial for the participating patients, and the proportion is significantly different between the locations ( P value < 0.001). The two groups also recorded significantly different proportions in favor of the issue. It was 83% among those with a priori knowledge against 67% among those without any a priori knowledge ( P value < 0.001). 8% of those who were not previously aware assumed that CTs may be harmful for the patients, whereas the proportion was less than 1% in the other group of respondents ( P value < 0.001). 79% of all respondents – 93% in the group with previous awareness and 73% in the group with no previous awareness – suggested creating more awareness about CTs among the patients. The difference was significant across locations ( P value < 0.001) as well as between groups ( P value < 0.000). 48% of the sample expressed their willingness to participate in CTs. This included 30% of those who were previously aware and 55% of those who were not, and the proportions significantly vary across locations and between groups.   Multivariate logistic regression analysis was applied with five perception-based questions as outcome variables and socio-demographic factors and locations as covariates. The results of the multivariate logistic regressions are summarized in . All the factors analyzed—gender, age, education, occupation, and place of residence—have an impact on some outcomes. Education was the most ubiquitous component. With the exception of willingness to engage in CTs, a higher education was found to be positively associated with favorable attitudes of CTs. Although they are more likely to see the societal advantages of CTs, people with greater education are also less inclined to take part in them. People with higher levels of education are more likely to understand that CTs take time. People in semi-urban or metropolitan settings are also more likely to be aware of the time taken for CTs than people in rural areas. The occupation is another universal component. Government employees were reported to have favorable opinions about CTs and to be eager to take part in them. Regardless of their socio-demographic standing, perceptions vary between areas.   This multi-centric cross-sectional survey evaluated the attitude and perception about CTs among the patients and patient bystanders (referred in the subsequent text as respondents), visiting the out-patient department of ophthalmology of the IOCTN sites. A total of 1260 respondents had participated in the survey. Among the socio-demographic profile of the respondents, gender, location of residence (rural, semi-urban, and urban), educational profile, and occupation of the respondents had differed significantly from each other in the study. The knowledge and perceptions about CTs among those who were already aware about CTs were evaluated. From this study, it was noticed that the majority (58%) of the respondents (i.e. patients and patient bystanders) were not aware of CTs. Balasubramanian et. al . (2013) and Joshi et al . (2013) had conducted a survey among Indian general population and reported that 60% participants were not familiar about CTs and only 25% participants were aware of CTs, respectively, which were quite similar to the observations in our study. Although about 42% of the respondents had said that they were aware of CT, not all respondents had clear knowledge of CT. The study also highlighted unawareness regarding major aspects of CT such as unawareness of voluntary power of an individual to participate in a CT (only 47%), unawareness regarding entitled benefits of free treatment, medical insurance during enrolment in a CT (only 47%), and only 16% of the respondents knew involvement of human subjects only in CT. These aspects of awareness could therefore prove to be a major barrier in the participation for future CTs. On the brighter side, if correct information regarding these aspects is highlighted and circulated to create awareness about CTs, it could be influential in mass participation of respondents in future CTs. A similar observation has also been highlighted by Joshi et al . (2013) and Shah et al . (2010). According to a meta-analysis study conducted by Shah et al. , in Indian population, participation in a CT was appealed by other factors such as financial benefits and free medical care. 60% of the respondents expressed CTs as risky affairs where human participants are treated as guinea pigs, which could be a major barrier in patient enrollment. Geana et al . (2017) had reported a survey regarding inner-city and rural patients’ awareness and perceptions of cancer CTs among Americans, wherein only a minority of the participants had expressed their feeling of being a guinea pig in an experiment while participating in a CT. With the fear of being an experimental lab rat or more of a guinea pig, the participants expressed that no one would want to be anybody’s guinea pig. Other studies have also reported that associating taking part in a CT as being a guinea pig represents a major barrier to patient enrollment in cancer CTs. A PARTAKE survey of Indian public by Burt et al . reported significant associations of having knowledge about CT among 175 Indian public of 8 locations of New Delhi, India, but the feeling of being an experimental guinea pig was found to be higher among the post-graduates and the highest-income groups. Social media (53%) were the most prominent platform in creating awareness among the respondents, followed by doctors (38%) in this study. There are reports of studies supporting and recommending that media and mass communication have a potential influence on public, and especially social media could be used as a platform to create awareness and promote public campaigns about CTs, which was also evident in our study. Moreover, involvement of CT participants in campaigns would help in improving rapport between the researchers and public, thereby transforming public view toward involvement in such studies. Furthermore, health care professionals such as doctors could also aid in improving the attitude and perception of patients and patient bystanders toward CTs. Equally, an important consideration is the incorporation of clinical research-related concepts into the educational curricula, which would build a significant impact on future generation. Our study observed that responses to all the knowledge and perception-based questions among those who had prior knowledge about CTs varied significantly across locations; however, some of the responses varied significantly as per gender, level of education, age, type of respondents (patients or bystanders), and place of residence. Chu et al. , 2015 reported a national survey of South Korean population focusing on the factors that were associated with willingness of participating in CTs. They revealed that awareness of CTs was significantly more prevalent among male respondents, 30–49 years of age, and among highly educated and residents of metropolitan cities and rural areas. The difference in perceptions between the two groups with and without a priori knowledge about CTs was also evaluated in this study. This study revealed 8% of those who were not previously aware assumed that CTs may be harmful for the patients, whereas the proportion was observed to be less than 1% in the other group of respondents who had prior knowledge ( P value < 0.001). Also, this study observed a significant difference between the two groups (with and without a priori knowledge about CTs) in the following aspects: (i) respondent’s willingness to participate in CTs, (ii) CTs being beneficial for the participating patients, and (iii) suggestion of creating more awareness about CTs among the patients. Burt et al . reported a PARTAKE survey highlighting the differences in perceptions among those who heard of clinical research and those who did not. The authors revealed a significant difference was observed in the two groups regarding human participants treated as guinea pigs (which was found to be higher in ‘heard’ category), with altruism being the reason for participation (which was found to be lower in ‘heard’ category) and voluntary participation (which was found to be lower in ‘heard’ category). A face-to-face survey among Korean general public regarding knowledge and perception about CT by Choi et al . reported perceptions among those who heard of CT and those who did not. The authors reported a higher percentage of the subjects in the “heard” group expressed a willingness to participate than in the “not heard” group. A study by Lee et al . demonstrated that patients with previous experience of CTs expressed greater willingness to participate in future. Moreover, the greater willingness to participate among patients who were aware of CTs in the study by Kim et al . increased weightage of positive association between CT awareness and willingness to participate. The proportion of subjects who expressed willingness to participate in CT was 39.3%, which was reported to be far below the rate in India. The authors pointed out a number of explanations were possible in this regard – the fact that a large proportion of the subjects who were not willing to participate expressed a lack of trust and fear as reasons for refusal and also a lack of belief in CT entities. Furthermore, this study also analyzed varying factors attributing to the respondents’ perception toward CTs through a multivariate logistic regression analysis. Perception of the respondents was found to be varying across locations (south, east, central, and west zones) irrespective of the socio-demographic status of the respondents. Also, the location of residence (rural, sub-urban, and urban) was another factor in shaping the perception of the respondents regarding CTs. Considering the fact that these IOCTN sites cover a diverse location (one site belonged from rural, two from semi-urban, and three from urban; one belonged from the central zone, one from the east zone, two from the south zone, and one from the west zone), the aspects such as (i) history of CTs conducted in these hospitals, (ii) areas adopted under community outreach of these hospitals as an initiative in advertising about CT through brochures and pamphlets in successfully attracting the public, (iii) accessibility of pharmaceutical companies for approaching CTs from these hospital locations, and (iv) preferential locations of pharmaceutical companies regarding specific target population as a mandatory requirement for conducting CTs could prove to be a major limitation for some of these hospitals on the basis of their location; therefore, a variation could definitely be observed in their track record of conducting the total number of CTs yearly, and hence, these variations would be reflecting as comparative more/less awareness, more/less participation, and shaping the perception regarding CTs positively/negatively among the public of each location of the IOCTN network. The study also highlighted education as the most pervasive factor in shaping the perception of the respondents regarding CTs. Sanguinetti et al. , Agu et al. , and Crepeau et al . reported that education influenced the understanding and/or consenting to participate in CTs in general. Occupation of the respondents was also found to be a ubiquitous factor in shaping the perception of the respondents regarding CTs in our study. Hussain-Gambles et al . had highlighted age as an attributing factor, which was not observed in our study in shaping perception regarding participating in CTs. The authors had reported younger adults were likely to have negative views on the necessity and participation in CTs in comparison to the middle-aged adults.   In conclusion, the present study reported the knowledge and attitude perception of patients and bystanders toward CTs. The majority (58%) were unaware about CTs, and the majority (71%) of total respondents (83% who had prior knowledge about CTs and 67% who were made aware during the survey) had expressed positivity in their attitude that CTs would be beneficial for the participating patients. The major concerns reported by the respondents were (i) CTs could be harmful and (ii) the time-consuming nature of CTs influences their willingness to participate in CTs. Utilizing the potentiality of media in informing and creating awareness to the public, advertising promotional feedbacks of CT participants who willingly agree to address public appearances, active participation of health care professionals (HCPs) in knowledge sharing about CTs, and showcasing the scope of CTs in academic curriculum would be some of the measures that could lead to a significant impact in the health-related concerns and participation of public in CTs. Financial support and sponsorship The study was funded by BIRAC-Department of Biotechnology, Govt. of India under National BioPharma Mission and Indian Ophthalmology Clinical Trial Network (IOCTN) project has also been funded by DBT-BIRAC. Conflicts of interest There are no conflicts of interest.   The study was funded by BIRAC-Department of Biotechnology, Govt. of India under National BioPharma Mission and Indian Ophthalmology Clinical Trial Network (IOCTN) project has also been funded by DBT-BIRAC.   There are no conflicts of interest.   