INTRODUCTION:

Although several studies on Indian clinical trial regulations have been accompanied [1-5], and articles published [6-10], little research has been carried out in the areas of clinical trial regulation. Two earlier studies have detailed the views and thoughts of researchers about the influence of past rules [1,2]. However, they ignored the opinions of other researchers, such as research assistants, coordinators, associates, and managers. As a result, the developing Indian clinical trial industry was affected by failure to comply with the regulations and reports of specific immoral clinical trials [11-13].

Learning the knowledge and opinions of these research professionals is essential because they serve as communicators and are a connective link between sponsors and patients in clinical trials. Therefore, their views are necessary to decide whether these trials are being administered as per the new rules. Moreover, acknowledging the current directives, these professionals perform an indispensable role in directing, reporting to their investigators [14]. Also, documenting for the ethics panel report of immoral clinical trials, notably on vulnerable peoples in India

Some of the unfair clinical trials in India were reported in the news previously [15-17]. According to that news report, thousands of Indians have died in unethical clinical trials over the past decade, and other 20,000-odd people have suffered adverse reactions. However, only 187 cases were offered compensation to the deceased families by pharmaceutical companies. Because in such clinical trials, they take advantage of loopholes in rules, loose oversight, and India’s enormous population of poor people who are often unaware of their rights as trial subjects. Therefore, in the near past, the government authorities of India had addressed these issues to establish the regulative mechanisms for reviewing clinical trials based on an exceptional level of investigation, media attention [18], non-governmental organizations involvement [12], hearings in the Supreme Court, and recommendations from an expert committee [6].

Furthermore, to advance clinical research in India by implementing an anticipated, clear, and valid direction for clinical trials [19, 20], the new rules have recently announced [21, 22]. These new regulations reportedly aim to ensure that the population has faster access to new drugs in India. Moreover, these new rules can modify the regulative aspect for the approval of new drugs and administer clinical trials in the country through a more accurate method, which may produce faster permissions.

As mentioned above, while minimal research observed in the literature about the opinions and perceptions of researchers concerning India's clinical trial regulations [1, 2]. The views of other relevant professionals, such as research assistants, coordinators, associates, and managers, were neglected in those studies. No study was described knowledge and views of those Indian researchers, including investigators and members of ethics boards, about current regulations. Thus, this study aimed to address this gap by describing the knowledge and views of Indian researchers concerning India's new rules.

MATERIAL AND METHODS:

The methodology adopted in this survey was based on earlier studies [23, 24], and the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) was utilized [25]. Described in detail about this survey study in the protocol [26].

Study population

In this study, male and female Indian researchers were chosen randomly from varied sources of all four nationwide zones (East, West, North, and South) between July 2019 and September 2019. Various sources described as the source of the Indian Society for Clinical Research, personal networks, hospitals, institutions, and LinkedIn. Researchers were defined as investigators, co-investigators, assistants, coordinators, associates, ethics board members (chairperson, secretary, other), and managers. The Institutional ethics board was informed about the intended survey and excused it from the evaluation process because it did not require participants' signed informed consent. This study was exempted from the ethics committee's inspection because of an observational survey involving minimal risks to participants [27]. No informed consent was required because it was anonymous data, i.e., no personal data was collected from the target persons.

Study questionnaire development

All of the questionnaires verified before were chosen from the previous studies [1, 2]. The permission to utilize these questionnaires in the present study was taken from the respective authors or journals. A widely used free form function of Google docs was used to develop each questionnaire [28] and finalized after considering recommendations from pilot testing. A link was created to enable participants to practice the survey online [29]. A Google form feature that restricts one response per person (respondents were required to sign in to Google) was enabled to block multiple access from the same person. Additionally, the feature "required" was enabled for all questions except for the following one: If you are a member of the ethics committee, what is your role? The amended questionnaire was validated by applying it to 10 researchers who worked at our university.

Procedure

The survey was announced on a social network (LinkedIn) [30]. Furthermore, an invitational email and messages were sent to all researchers in the Indian Society for Clinical Research, personal networks, hospitals, institutions, and LinkedIn. Invitational email and information consisted of the survey's goal, methods, and a link to the survey questionnaires. As mentioned above, all questions are required to answer except one. An option ‘do not know’ enables respondents to skip questions. In the invitation, we mentioned that participation was entirely voluntary and anonymous and that it would not require the provision of any identifying information except age and gender.

Further, the email reinforced that involvement in the research was of great importance to assess researchers' present knowledge and views regarding the new regulations and to promote clinical research in India. Email reminders were transferred to all researchers to assure the maximum number of answers after two weeks interval from the first invitation. Respondents were inadequate to review or amend their responses once clicking on the submit button. All responses were accessed only by the researcher.

Outcome

An enhanced understanding of the knowledge and views of researchers concerning the current new rules was an outcome of this study. The questions of the measure that assessed this outcome are exhibited in Table 1. Some questions were excluded from the analysis due to no or low response.

Table 1. Questions of the measure

No.	Question
Q1	Are you aware of the new drug and clinical trials rule of 2019 in India? A) Yes, B) No.
Q2	Are your manager and the clinical staff involved in clinical trials aware of the new rules of 2019? A) Yes, B) No.
Q3	If so, how aware do you think they are of the implications that this might have on clinical trials? From 1=not at all to 5= a lot.
Q4	Would it be useful to share these new rules with the principal researchers and co-researchers in your department to understand whether there are any issues regarding the rules at all levels of their research, and to understand their level of awareness and opinions? A) Yes, B) No.
Q5	If you are not aware of the new drugs and clinical trial rules of 2019 in India, do you think it would be useful to have information about it? A) Yes, B) No.
Q6	What do you think is the best way to keep up to date? A) Personal reading, B) Internet, C) Networking, and D) Other.
Q7	What do you think will be the most important consequences of the new rules? A) It will help the conduct of clinical trials, B) It will hinder the conduct of clinical trials, C) It will not have a significant impact on the conduct of clinical trials, and D) Other.
Q8	Do you think that the adoption of the new rules will change your way of working? A) Yes, B) No.
Q9	Do you think that the staff of the Ethics Committee or scientific boards are ready to face the new challenges of the new rules of 2019? A) Yes, B) No, C) Mostly, and D) A little.
Q10	Is the new rule on reducing the timeline of the clinical trial of new drugs appropriate? A) Yes, B) No, and C) Maybe.
Q11	Is the new rule on phase IV appropriate? A) Yes, B) No, and C) Maybe.
Q12	Is the new rule regarding free post-trial drug access appropriate? A) Yes, B) No, and C) Maybe.
Q13	Is a new rule on clinical trial approval validity appropriate? A) Yes, B) No, and C) Maybe.
Q14	Is the new law on welcoming equality proper? A) Yes, B) No, and C) Maybe.
Q15	Are the new rules of 2019 on adverse severe events and compensation relevant to what has to be reported, how, and how the timelines should be provided? A) Strongly Agree, B) Agree, C) Neutral, D) Disagree, and E) Strongly disagree.
Q16	What kind of clinical trials will the new rules impact the most? A) Profit studies, B) Non-profit studies, and C) Both.
Q17	As a research professional, what is your opinion on the new rules of 2019? A) Strongly Agree, B) Agree, C) Neutral, D) Disagree, and E) Strongly disagree.
Q18	What is your general opinion about the new rules of 2019 India? A) Highly positive, B) Highly negative, C) Unconcerned, and D) No precise idea.

Analysis

Descriptive statistics such as means and standard deviation (SD) were calculated for continuous variables. In contrast, counts and percentages were used with categorical variables. The researchers’ knowledge and views of each questionnaire were computed in frequency and rates. The analyzed data were presented in tabular and chart formats. All analyses were performed utilizing the statistical analysis software (SAS) version 9.4 for Windows (SAS Corporation Inc., NC, USA).

RESULTS:

In total, 106 researchers answered the survey. The demographic features of the researchers are shown in Table 2. The average age of researchers was 33.5 (SD=11.7) years. Most researchers were men (69%). The majority of them belonged to South India and had a researcher or co-researcher role (22.7%).

Table 2. Researchers' demographic backgrounds

Characteristics	Mean (SD) OR N (%)
Age in year	33.5 (11.7)
Sex
Men	73 (69)
Women	33 (31)
Region
North	28 (26.4)
South	53 (50)
West	13 (12.3)
East	12 (11.3)
Job role
Researcher or Co-researcher	24 (22.7)
Research assistant	20 (19)
Research coordinator	16 (15)
Research associate	16 (15)
Manager	9 (8.5)
Chairperson of EC	7 (6.6)
Secretary of EC	4 (3.8)
Other in EC	10 (9.4)

Note. EC = Ethics Committee.

Off 106 researchers, 75 (70.8%) researchers, and 65 (61.3%) their managers and clinical staff grasped the new rules. Further, 101 (95.3%) researchers said that sharing the new rules with co-researchers, or their staff at all levels or their levels of expertise and views were useful. Off 106, 93, and 82 researchers (92.1% and 82%) said that it is useful to have information about new regulations, if not ware, and changes the way of work (Table 3).

Table 3. The knowledge of Indian researchers regarding Questions 1, 2, 4, 5, and 8 (Q1, Q2, Q4, Q5, and Q8, respectively) of Table 1.

Awareness	From Table #1
Awareness	Q1 (%)	Q2 (%)	Q4 (%)	Q5 (%)	Q8 (%)
Yes	75 (70.8)	65 (61.3)	101 (95.3)	93 (92.1)	82 (77.4)
No	31 (29.2)	41 (38.7)	5 (4.7)	8 (7.9)	24 (22.6)

Note. Q1 = Are you aware of the new drug and clinical trials rule of 2019 in India? Q2 = Are your manager and the clinical staff involved in clinical trials aware of the new regulations? Q4 = Would it be useful to share these new rules with the principal researchers and co-researchers in your department to understand whether there are any issues regarding the rules at all levels of their research, and to understand their level of awareness and opinions? Q5 = If you are not aware of the new drugs and clinical trial rules of 2019 in India, do you think it would be useful to have information about it? Q8 = Do you think that the adoption of the new rules will change your way of working?

Figure 1 illustrated the knowledge and views of Indian researchers about the implications of the new rules (Fig. 1A), by what means they would instead be kept up to date regarding the regulations (Fig. 1B), whether the staff of the ethics board was ready to face the new challenges of the new rules (Fig. 1C), and the impact of the new regulations on each type of clinical trial (Fig. 1D). The majority of the researchers answered that it was useful to know the new regulations (92.1%); some responded (36 out of 106) that the rules had some implications ("somewhat" answer was 34.6%; Fig. 1A); near half of the researchers (49 out of 106) would instead be kept up to date through the internet (46.2%; Fig. 1B). Of 106 researchers, 54 researchers (50.9%) reported that staff of the ethics board are ready to face the new challenges of the new rules (Fig. 1C). More than half (71 out of 106) of the researchers (67%) stated that the new regulations would often affect the profit clinical trial studies (Fig. 1D).

Table 4. The knowledge of Indian researchers about Questions 10-13 (Q10-13) of Table 1

	Clinical trial’s
	Reducing timeline (%)	Phase IV (%)	Free post-trial drug access (%)	Approval validity (%)
Yes	36 (63.2)	27 (47.4)	32 (56.1)	27 (47.4)
Maybe	18 (31.6)	27 (47.4)	22 (38.6)	27 (47.4)
No	3 (5.2)	3 (5.2)	3 (5.3)	3 (5.2)

Note. Q10 = Is the new rule on reducing the timeline of the clinical trial of new drugs appropriate? Q11 = Is the new rule on phase IV appropriate? Q12 = Is the new rule regarding free post-trial drug access appropriate? Q13 = Is a new rule on clinical trial approval validity appropriate?

The knowledge of Indian researchers on the adequacy of the new rules and their overall opinion on them are shown in Table 5. Out of 106 researchers, 31 and 37 researchers (54.5% and 64.9%) were accepted the modifications of welcoming equality and serious adverse events and compensation, respectively. Overall, 59.6% (34 out of 106) of the researchers agreed with the new rules. Generally, 91 out of 106 researchers (87.5%) believed that the new regulations were extremely beneficial to the advancement of clinical trial studies in India (Fig. 3).

Table 5. The knowledge of Indian researchers regarding Questions 14, 15, and 17 (Q14, Q15, and Q17, respectively) of Table 1

	Strongly agree (%)	Agree (%)	Neutral (%)	Disagree (%)	Strongly disagree (%)
Welcoming equality	8 (14.0)	31 (54.4)	12 (21)	0 (0.0)	6 (10.5)
SAE and compensation	14 (24.6)	37 (64.9)	6 (10.5)	0 (0.0)	0 (0.0)
Overall perspective on the new rules of 2019	14 (24.6)	34 (59.6)	6 (10.5)	3 (5.3)	0 (0.0)

Note. SAE=Serious adverse event. Q14 = Is the new law on welcoming equality proper? Q15 = Are the new rules of 2019 on adverse severe event and compensation relevant concerning what has to be reported, to whom, how, and how the timelines should be provided? Q17 = As a research professional, what is your opinion on the new rules of 2019?

Fig.3. General researchers’ knowledge about the new rules on drugs and clinical trials of 2019 in India (Question 18 [Q18] of Table 1).

Note. Q18 = What is your general opinion about the new rules of 2019 India?

DISCUSSION:

The present study reported the knowledge and views of Indian researchers concerning India's new rules. The results of this study show that researchers deemed knowledge about the new regulations useful. Also, they believe that sharing them with co-researchers, their staff at all levels, or their levels of helpful expertise. Furthermore, they think that keeping up to date through the internet could help to change their way of work. Moreover, they believe that the staff of the ethics board are ready to face the new challenges of the new rules.

In this study, most researchers said that the new regulations would promote clinical trials in India. The majority of the researchers greeted critical progress in the current new rules, including the decrease in the timeline, in phase IV of clinical trials, in the open post-trial drug path, permission validity, welcoming equality, serious adverse events, and compensation. These results may be revealed that the new rules are beneficial to the growth of clinical research and the pharmaceutical industry in India. However, another possible explanation is that these results show that the new regulations force improve the ethical standard and patients' benefits, particularly those of vulnerable cases.

Nevertheless, this survey has some flaws. First, the way the study was sampled from the total population may not be generalizable to the rest of the national community. The future survey is required on a larger sample across India to generalize the knowledge and views of researchers on India's new drug and clinical trial regulations of 2019. Also, further research should be initiated at the national level to represent the knowledge of Indian researchers on the current new rules through interviews. Second, surveys are limited by their cross-sectional design, which only acknowledges ascertaining relationships, but no causalities. A further study with more focus on to determine causalities is therefore suggested. Third, this study has a biased sampling error. Also, the survey’s sample was a non-probability sample. It does not give all the individuals in the population equal chances of being selected. Hence, some variations when drawing results can come up. Finally, researchers who did not participate in the survey might aware or may not be mindful of the new rules. Also, we did not ask the participants who reject new rules refused to do so. In general, this is crucial information in studies where such representatives are not represented.

The main strength of this survey study is that participation was entirely voluntary and anonymous. In this anonymous survey settings, the subject is assured that their responses will not be linked to them, and they are not asked to divulge sensitive information directly to a surveyor. In this survey study, anonymity was established through self-administration of the electronic survey via computer, smartphone, or tablet [31]. However, self-administered data has its limits, but social desirability is even more relevant in interviewer-administered data [32].

Similarly, previous studies also investigated the opinions and perceptions of researchers and members of the ethics board regarding the possible problems of the last regulatory guidelines issued in 2016 [1, 2]. These studies showed that researchers generally concurred with the regulations. However, members of the ethics board felt that regulations brought challenges to oversight and monitoring research that were carried out at the site. However, this was the first survey that the changes stated here are the only ones found between these studies. This is the single study that described the knowledge and views of research assistants, coordinators, associates, and managers.

CONCLUSIONS:

Most researchers are aware of India's recent new regulations. They embraced reforms and accepted that the new rules are highly beneficial to the growth of clinical trials in India. Also, they reported that updating the rules through the internet that would allow them to change their way of working. Overall, the outcomes of this study show that ethical standards can be improved and benefit patients, especially those under vulnerable circumstances. Also, findings intimate that in general, the new rules may serve to extend clinical research and the pharmaceutical industry in India by advancing clinical trials and the permission of new drugs. Future studies are warranted on a more comprehensive sample at the national level to demonstrate the knowledge and views of Indian researchers on the topic.

LIST OF ABBREVIATIONS:

CHERRIES: Checklist for Reporting Results of Internet E-Surveys; CDSCO: Central Drugs Standard Control Organization; EC: ethics committee; SD: standard deviation; SAS: statistical analysis software; USA: United States of America

ACKNOWLEDGMENTS:

The authors would like to thank the study participants. Also, the corresponding author extends his appreciation to the Research Centre, College of Applied Medical Sciences, and the Deanship of Scientific Research at King Saud University for supporting this research.

CONFLICTS OF INTEREST:

None declared.

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Received on 02.06.2020 Modified on 07.07.2020

Research J. Pharm. and Tech. 2020; 13(9):4179-4184.

DOI: 10.5958/0974-360X.2020.00738.6