Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & ISI's SCI  
Users online: 2669  
Home | Subscribe | Feedback | Login 
About Latest Articles Back-Issues Articlesmenu-bullet Search Instructions Online Submission Subscribe Etcetera Contact
 
  NAVIGATE Here 
  Search
 
  
 RESOURCE Links
 ::  Similar in PUBMED
 ::  Search Pubmed for
 ::  Search in Google Scholar for
 ::Related articles
 ::  Article in PDF (450 KB)
 ::  Citation Manager
 ::  Access Statistics
 ::  Reader Comments
 ::  Email Alert *
 ::  Add to My List *
* Registration required (free) 

  IN THIS Article
 ::  Abstract
  ::  Introduction
  ::  Material and Methods
  ::  Results
  ::  Discussion
 ::  References
 ::  Article Figures
 ::  Article Tables

 Article Access Statistics
    Viewed814    
    Printed265    
    Emailed0    
    PDF Downloaded22    
    Comments [Add]    

Recommend this journal


 


 
  Table of Contents     
ORIGINAL ARTICLE
Year : 2023  |  Volume : 69  |  Issue : 1  |  Page : 21-26

An audit of questions asked by participants during the informed consent process for a phase 2/3 COVID-19 vaccine regulatory study at a tertiary referral centre


Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India

Date of Submission31-Dec-2021
Date of Decision03-Mar-2022
Date of Acceptance26-Mar-2022
Date of Web Publication06-Oct-2022

Correspondence Address:
Dr. N J Gogtay
Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpgm.jpgm_1216_21

Rights and Permissions


 :: Abstract 


Objective: To evaluate questions asked during the informed consent process by adult participants in a COVID-19 vaccine regulatory study conducted at our center in 2020.
Methods: After approval by the IEC, informed consent documents and consent narratives were evaluated. We collated the total number and nature of questions. We then looked at the association between education, gender, socio-economic status, employment status, the language of consent, and number of questions. Between-group comparison (female vs male, unemployed vs employed, primary school vs secondary school vs graduate vs post-graduates, upper vs upper-middle vs middle vs lower middle vs lower) for the number of questions asked was done using univariate analysis followed by multivariate regression analysis with post hoc Tukey's test. Independent variables were gender, employment status, education and socioeconomic status and the dependent variable was the number of questions asked by the participant. All analyses were done at 5% significance. Content analysis was done in addition by creating categories after evaluation and coding them.
Results: A total of N = 129 consents from the same number of participants were evaluated. A total of N = 127/129 participants asked at least one question. Sixty-seven percent of participants asked questions related to the study procedure, followed by 44.9% of participants who asked questions related to the safety of vaccine or placebo. A total of N = 295 questions were asked by the 127 participants. In content analysis, 149/295 (50.5%) questions were on study-related procedures followed by one quarter 76/295 (25.8%) based on safety associated with Investigational Product. Very few participants [2.4%] asked about post-trial access as the regulatory trial was a placebo-controlled trial. None of the independent variables were found to be associated with the number of questions.
Conclusion: The majority of the questions asked by the participants were about study-related procedures and vaccine safety. No association was found between any of the independent variables and the number of questions asked. However, there were differences in the demographics of the trial participants between the pandemic and pre-pandemic era.


Keywords: Compensation, content analysis, safety


How to cite this article:
Chaudhari V L, Godbole C J, Bendkhale S R, Desai N N, Gogtay N J, Thatte U M. An audit of questions asked by participants during the informed consent process for a phase 2/3 COVID-19 vaccine regulatory study at a tertiary referral centre. J Postgrad Med 2023;69:21-6

How to cite this URL:
Chaudhari V L, Godbole C J, Bendkhale S R, Desai N N, Gogtay N J, Thatte U M. An audit of questions asked by participants during the informed consent process for a phase 2/3 COVID-19 vaccine regulatory study at a tertiary referral centre. J Postgrad Med [serial online] 2023 [cited 2023 Feb 1];69:21-6. Available from: https://www.jpgmonline.com/text.asp?2023/69/1/21/358382





 :: Introduction Top


The International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice guidelines (ICH GCP) defines informed consent as a process by which a subject voluntarily confirms his or her own willingness to participate in a particular trial after having been informed of all aspects of the trial that are relevant to the subject's decision to participate.[1] A crucial aspect of this process is that investigators should provide adequate time to potential participants to ask questions, give them sufficient time to understand all aspects of the study, and clarify all queries to the participant's satisfaction.[2]

Our institute was part of a bridging study for COVISHIELD™ CTRI/2020/08/027170 which began in India in September 2020 during which we captured questions raised by the participants during the consent process from the narratives of the informed consent process. An analysis of these questions would help investigators and policy makers understand the concerns that participants have and also evaluate the adequacy of the informed consent process for the COVISHIELDTM vaccine study. This formed the objective of our study.


 :: Material and Methods Top


Ethics

We obtained approval for the study protocol along with a consent waiver from the Institutional Ethics Committee [Study reference - EC/OA-40/2021]. The permission to analyze the informed consent documents and the written consent narratives of the participants at our site was also obtained from the sponsor.

Study design and duration

The study was a retrospective audit.

Eligibility criteria

Inclusions were participants who consented and completed the consent process. Those who declined consent were excluded.

Study procedure

We analyzed the ICDs of the participants [which were either in English or Hindi or Marathi language] and the written consent narrative. This refers to the document which captures the entire informed consent process along with the questions asked by the participants during the consent process and the answers given by the person obtaining informed consent. The physicians who were part of the consent process and who themselves were familiar with written and spoken English, Hindi, and Marathi with the requisite qualifications. The confidentiality of the individual participants was maintained using unique identifiers. Four authors evaluated the narratives independently and the quality check was done by the senior authors.

Study tools

Information gleaned from the Informed Consent Document [ICD] and consent narratives- The following information was collated - participant age, gender, educational status, occupation, annual income, and date and time of consent. The start and stop time was taken from the consent narrative.

Classification of questions identified in the consent narratives

We classified the questions asked under the following domains –efficacy and safety of the Investigational Product (IP), study procedure, scientific aspects of the protocol, post-trial access, payment for participation, IP-related questions, and any additional questions asked. We based this on the Indian Council of Medical Research's (ICMR) National Guidelines for Biomedical and Health Research involving Human Participants (2017),[3] which outlines the essential elements in an ICD.

Assessment of education and socio-economic strata

Based on the school education system in India, educational status was divided into four categories- primary and middle school (up to 8th grade education), high and higher secondary school (9th–12th grade education), graduates (completed college with a bachelor's degree) and post-graduates (completed college with a master's degree).[4] Based on the updated BG Prasad socioeconomic scale 2020,[5] the participants were divided into five socioeconomic categories- upper [Indian rupees (INR) >7,533/months], upper middle (INR between 3,766-7,532), middle (INR between 2260-3765), lower middle (INR between 1,130-2,259) and lower (INR < 1130).

Outcome measures

The outcome measures were- number of total questions asked by the participants [dependent variable] including all domains, the proportion of participants who asked questions in each of the domains.

Sample size

The sample size for our site in the multicentric regulatory trial was N = 100 for which, we had screened N = 129 participants who had given consent for the regulatory trial and none of the potential participants had declined the consent in the regulatory trial. Hence, as per the eligibility criteria, N = 129 thus formed the final study sample.

Statistical and content analysis

Both descriptive and inferential statistics were applied to the data. Categorical data (for example - gender, employment status) was presented as proportions, while numerical data (for example, number of questions asked, time taken to consent) was presented as median (range). Between group comparison (female vs male, unemployed vs employed, primary school vs secondary school vs graduate vs post-graduates, upper vs upper middle vs middle vs lower middle vs lower) for the number of questions asked was done using univariate analysis followed by multivariate regression analysis with post hoc Tukey test. Independent variables were - gender, employment status, education, and socioeconomic status, and the dependent variable was the number of questions asked by the participant. All statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 20, IBM Corporation, Armonk, New York and the statistical significance was set at <0.05. Content analysis[6] was done by creating the following categories after going through all consent narratives and Informed Consent forms - Study procedure; Safety and risk; Payment related; Scientific aspects of the study; and post-trial access. Each category was subsequently coded independently by four authors. A consensus was reached amongst all the authors about the coding and the categories.


 :: Results Top


Demographics

A total of N = 129 adult healthy participants with a median [range] age of 42 years [19-67] formed the final sample. Among the consent narratives, 118/129 (91.5%) were obtained from men and 11/129 (8.5%) were obtained from women. The consents were largely obtained in English 98/129 (76%) followed by Marathi 23/129 (17.8%) and only 8/129 (6.2%) were obtained in Hindi. The median time (range) taken for consenting the participants was 32 (23–86) minutes. A total of five physicians obtained consent from the potential participants.

Of these 129 participants, only one participant was illiterate and we had an impartial witness.

Therefore, amongst the total n = 128 literate participants, 60/128 (46.9%) participants were graduates, 51/128 (39.8%) were post-graduates, 15/128 (11.7%) were those with secondary school education, and only 2/128 (1.6%) had a primary school education. A total of 121/129 (93.8%) participants were employed and while the remainder of 8/129 (6.2%) were unemployed [Table 1]. The majority 120/129 (93%) of the participants were from the upper economic status while only one (0.8%) belonged to the upper-middle and the rest (8, 6.2%) were from the lower economic strata.
Table 1: Demographics (n=129)

Click here to view


Questions asked - The total number of questions asked by the 129 participants was N = 295 with a median of two questions asked per participant (range 0–11).

  1. Number of questions asked [Table 2]: A total of 127/129 (98.5%) participants asked questions while two participants did not ask a single question. Of the 127, 103/127 (81.1%) asked more than two questions, 23/127 (18.1%) asked at-least one question, while 01/171 (0.8%) asked more than 10 questions.
  2. Nature of questions asked (n = 127): A total of 85/127 (66.9%) asked questions related to the study procedure, followed by 64/127 (50.4%) participants who asked questions related to the safety of vaccine/placebo. A total of 35/127 (27.6%) asked questions about the science of the study, 27/127 (21.3%) asked questions related to payment for participation, 7/127 (5.5%) asked questions about risk and additional research respectively, and 3/127 (2.4%) asked about the components of the IP and post-trial access respectively [Figure 1].
  3. Content analysis [Table 2]:
  4. Table 2: Content analysis of questions (n=295) asked by the participants

    Click here to view
    Figure 1: Nature of questions asked (n=127)

    Click here to view


    We categorized questions asked into five main categories. These were - study procedure, safety and risks, payment related, scientific aspects, and post-trial access. These categories were further delineated using several codes [total 18 codes, [Table 2]]. Of the total N = 295 questions asked by the participants, half of the 149/295 (50.5%) questions were on study-related procedures followed by one quarter 76/295 (25.8%) based on safety and risk associated with IP. Whereas, approximately 10% of questions were related to payment and scientific aspects of the study. Only 15/295 (5.0%) questions were asked related to post-trial access of the vaccine.

  5. Impact of the variables on number of questions being asked: No statistically significant association was found either in the univariate or multi variate analysis between the dependent and independent variables.



 :: Discussion Top


In the present audit, we evaluated N = 129 informed consent forms and their consent narratives from the participants of the phase 2/3 vaccine COVISHIELD study who were recruited from September to October 2020 in Mumbai. Ninety nine percent of participants asked questions with the median number of questions asked is two (0–11). The majority of the participants were well educated [87%], employed [94%], and from upper socio-economical strata [93%]. The majority [67%] of the questions asked by participants were related to the study protocol followed by the safety of the investigational product [45%]. The predominantly male population in the study again underscores the fact that women are generally underrepresented in clinical trials[7],[8] for reasons identified earlier. The novelty of the study lies in it being conducted during a pandemic setting.

When we compared this study to a previous study done by Saxena et al.,[2] which evaluated a total of N = 297 consent narratives in five regulatory studies conducted over a year in the pre-pandemic situation at our center, they found that participation of women was more as compared to our study (37 vs 8%; P < 0.0001). Similarly, 92% of the consent forms were signed in the local language vs only 24% in our study [P < 0.0001]. In their study, only 18% of the participants were graduates relative to 86% in our study [P < 0.0001]. As regards employment, 63% were employed in the study by Saxena et al. relative to 94% in our study [P < 0.0001]. Details are presented in [Table 3]. We hypothesize that the significant differences seen are due to the fact that the pandemic led to unprecedented media coverage of all COVID -19 vaccine trials leading to the participation of a largely urban population, and employed English speaking male graduates despite the institution being one that largely caters to the lower socio-economic strata.
Table 3: Comparison with historical data available as (pre-pandemic situation- Saxena et al. [2]) vs present study conducted in COVID-19 pandemic

Click here to view


Nature of questions: In our study, the majority of questions asked were related to the study procedure (67% vs 49%; P = 0.009), while in the previous study they were related to safety (50% vs 77%; P < 0.0001). In the present study, the participants focused on science (28% vs 6%; P < 0.0001). In the present study, the participants focused on science (28% vs 6%; P < 0.0001) of the study, payment) of the study, payment-related issues (21% vs 16%; P = 0.36) but there was limited concern about post trial access (2% vs 6%; P = 0.14). This difference in the nature of questions asked was found to be statistically significant [P < 0.0001; x2 = 48.2 and dF = 7]. The probable explanation for this difference could be the limited knowledge about the corona virus in the early stages of the pandemic when the vaccine study was undertaken leading to a focus on science from an educated male population. Also, given the fact that post trial access was clearly stated in the consent form, this may have been less of a concern.

In the present study, we found that nearly half of the total questions asked and two-thirds of the consent narratives had questions related to study procedures/protocol related such as 'How many visits do I require to complete the study; Where should I come for my next visit; What will happen if I miss my follow up visit date; What are my responsibilities as a research participant; and How much time I have to stay after vaccination?'. This could be attributed to the lockdown restrictions during the pandemic which made the potential participants wary of the travel to the site for the study visits. The potential participants also expressed their concern about the 25% chance of getting a placebo by asking questions such as 'Will I get vaccine or placebo; What is the possibility that I will get the study vaccine?'. This might be due to the surging spread of the disease making the potential participants feel both vulnerable and apprehensive and this could have impacted the nature and type of the questions asked. The potential participants were also worried about the site of vaccination and the number of times the blood will be collected.

Half of the potential participants asked questions about the safety of the vaccine or the placebo-like- 'What are the possible side effects of the study vaccine/placebo; Will the adenovirus in the vaccine cause me harm; Does the vaccine contain live coronavirus and can cause covid 19 disease and What happens if there is a serious/life threatening side effect?' indicating that safety featured high on their list of questions given the limited understanding at the point of the vaccine study. The lack of association between the number of questions asked by the potential participants and independent variables is likely due to the small sample size and considerable homogeneity [English speaking, well-educated and male participants] in our population which are the major limitations of our study. The present study is also limited by being from a single center in a metropolis and with just one historical comparator and that too from our own center.

In summary, our audit found that in a regulatory COVID-19 vaccine trial majority of the questions/doubts [67%&x93; asked by the participants during the informed consent process were about study-related procedures followed by the safety of the COVID vaccine. We did not find an association between the number of questions asked during the consent process and their age, gender, educational status, occupation, and socioeconomic status.

Acknowledgements

We are grateful to Dr Unnati Saxena for providing the data on the demographic characteristics and questions asked by the participants in pre-pandemic era in the form of publication. We are also grateful to all the participants in our study. The authors are also grateful to Dr Milind Nadkar, Professor and Head of Medicine, for the help and support provided during the conduct of this original regulatory study.

Financial support and sponsorship

Nil.

Conflicts of interest

None declared.



 
 :: References Top

1.
fda.gov [Homepage on the internet]. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for human use (ICH), Integrated addendum to ICH E6 (R1): Guideline for Good Clinical Practice E6 (R2). 2018 [updated 2022 Mar 02]. Available from: https://www.fda.gov/files/drugs/published/E6%28R2%29-Good-Clinical-Practice--Integrated-Addendum-to-ICH-E6%28R1%29.pdf. [Last accessed on 2022 Mar 03].  Back to cited text no. 1
    
2.
Saxena U, Bose D, Maurya MK, Gogtay NJ, Thatte UM. An audit of questions asked by participants during the informed consent process for regulatory studies at a tertiary referral centre – An analysis of consent narratives. Clin Ethics 2021;16:144-50.  Back to cited text no. 2
    
3.
main.icmr.nic.in [Homepage on the internet]. Indian Council of Medical Research. National Ethical Guidelines for Biomedical and Health Research Involving Human Participants. 2017 [updated 2022 Mar 3; cited 2022 Mar 3]. Available from: https://main.icmr.nic.in/sites/default/files/guidelines/ICMR_Ethical_Guidelines_2017.pdf.  Back to cited text no. 3
    
4.
Sharma R. Revised Kuppuswamy's socioeconomic status scale: Explained and updated. Indian Pediatr 2017;54:867-70.  Back to cited text no. 4
    
5.
Mathiyalagen P, Davis P, Sarasveni M. Updated BG Prasad socio-economic classification: The 2020 update. Indian J Pediatr 2021;88:76–7.  Back to cited text no. 5
    
6.
Bengtsson M. How to plan and perform a qualitative study using content analysis. Nursing Plus Open 2016;2:8-14.  Back to cited text no. 6
    
7.
Lobato L, Bethony JM, Pereira FB, Grahek SL, Diemert D, Gazzinelli MF. Impact of gender on the decision to participate in a clinical trial: A cross-sectional study. BMC Public Health 2014;14:1156.  Back to cited text no. 7
    
8.
Steinberg JR, Turner BE, Weeks BT, Magnani CJ, Wong BO, Rodriguez F, et al. Analysis of female enrollment and participant sex by burden of disease in US clinical trials between 2000 and 2020. JAMA Netw Open 2021;4:e2113749-62.  Back to cited text no. 8
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
Print this article  Email this article
 
Online since 12th February '04
2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
Published by Wolters Kluwer - Medknow