Development And Evaluation Of The Informed Consent Instrument For Trials Of Chinese Medicine

ObjectiveThe development of Chinese Medicine(CM)is inseparable from clinical trials,and all clinical trials require the informed and voluntary participation of subjects as the premise.Informed consent is the main measure to protect the rights and safety of subjects in clinical trials.However,many studies had shown that the status quo of informed consent was not satisfactory,especially for trials of CM.Because of the particularity of CM,the subject’s understanding of this aspect was often ignored during informed consent.The effect of informed consent was difficult to truly achieve.On the other hand,the current evaluation of informed consent basically adopted the methods of status analysis and qualitative research analysis,which took a long time,the analysis was also complicated,and it was not convenient for mutual comparison.How to achieve a simple,convenient and objective evaluation of the informed consent for specific trials had not been reported in China.The purpose of this study was to develop an effective,reliable,and simple patient used questionnaire for evaluating the quality of informed consent in trials of CM.The questionnaire will be used as an objective evaluation tool to identify problems that need to be improved in the informed consent process.It can be used to achieve a horizontal comparison of informed consent in different CM trials.It can also be used to evaluate the impact of different interventions on the informed consent process,and be used as a tool for evaluation of investigator training or a tool of ethics committee and quality management department to monitor the informed consent process.We hope that the evaluation of informed consent by this questionnaire can improve the quality of trials in CM,protect the rights and safety of subjects,and promote the academic development of CM.MethodsThis study referred to the methods and procedures for the development and evaluation of quality of life questionnaires and patient-reported outcome measures.To develop and evaluate the "Informed Consent Questionnaire for Trials of Chinese Medicine"(ICQ-TCM),we adopted many methods,such as literature review,qualitative research(in-depth interviews),expert consultation,and cross-sectional surveys of subjects.By review relevant domestic and foreign laws and regulations,guidelines,and literatures related to informed consent,combined with our country’s cultural background and the characteristics of trials of CM,items were listed according to the theoretical framework of the questionnaire.In addition,in order to develop the items of CM,we interviewed patients who had participated in trials of CM and had good communication skills for interviews to understand their experiences and opinions in participating in trials,especially in CM trials.After the item pool was established,the Delphi method was adopted,and after two rounds of expert consultation,items were screened from the perspective of importance to form the questionnaire.Using a cross-sectional survey design,through investigation of a small sample of patients who had participated in trials of CM,different statistical methods such as discrete trend analysis,correlation coefficient analysis,factor analysis and stepwise regression analysis were used to select items,and finally formed a test version of the questionnaire.The test version questionnaire was tested among a wider range of subjects to evaluate the feasibility,reliability,and validity.Results1.Formation of item poolThe first step was to set up a nominal group and a focus group,which can clarify and define the concept of ICQ-TCM.According to the three principles of informed consent.information,comprehension,and voluntariness,combined with the characteristics of trials in CM,the questionnaire should include at least five domains:completeness of the information,comprehension of the information,voluntariness,communication satisfaction and general evaluation.The nominal group listed items according to the theoretical framework of the questionnaire and combined with results of interviews with 6 patients.The final item pool was developed,which 38 items were grouped under the domain of completeness of information(including 5 items of CM),10 items under comprehension of the information(including 1 item of CM),10 items under voluntariness,9 items under communication satisfaction(including 1 item of CM),2 items under general evaluation,and the other 2 items(open questions,including 1 item of CM).2.Experts consensusTotally 21 experts across the country were consulted to select items from the perspective of importance.We conducted twice consensus investigations of experts in December 2020 and January 2021.According to the consultation results,the proportion of experts who agreed that the five domains should be included in the questionnaire exceeded 60%,so there was no change in domain.After the first consultation.50 items were selected from the initial item pool.At the second consultation,42 items finally remained.There were 21 items grouped under the domain of completeness of information,8 items under comprehension of the information and voluntariness respectively,4 items under communication satisfaction and 1 item under general evaluation.3.Pilot test and item selectionAfter the preliminary questionnaire was formed,from April 2021 to June 2021,48 patients who had participated in different trials of CM were investigated from 4 regions across the country,and a total of 46 questionnaires were returned.The average age of the patients was about 47 years old.The patients with level of education below junior middle school accounted for 60.8%.Four statistical methods,discrete trend analysis,correlation coefficient analysis,factor analysis and stepwise regression analysis were used to select items.The item would be deleted if three methods recommended deletion of it.We deleted 2 items and remained 40 items after the analysis,including 21 items under the domain of completeness of information,8 items under comprehension of the information,7 items under voluntariness,3 items under communication satisfaction and 1 item under general evaluation.The preliminary evaluation of the questionnaire was also conducted.The split-half reliability was 0.901.The Cronbach coefficient scale factor was 0.904,which was greater than 0.8.It was indicted that the reliability was good.The scale had good content validity,but the results of construct validity was inconsistent with the theoretical framework of the questionnaire.A larger sample of investigation was needed for further verification.4.On-site test and evaluation of the questionnaireFrom July 2021 to August 2021,a total of 198 patients were enrolled from 4 different regions to measure the reliability and validity of the formal questionnaire(beta version).One incomplete questionnaire was excluded,and a total of 197 questionnaires were included in the analysis.The average age of the patients was about 51 years old.The patients with level of education below junior middle school accounted for 48.7%.The results showed that the average time to finish the questionnaire was about 14.8 minutes,the shortest time was 3 minutes,and the longest time was 45 minutes.The time to fill out the questionnaire was directly related to the patients’educational level,which also indicated that the expression of the items should be further improved in the future.The test-retest reliability of the questionnaire was 0.892.The split-half reliability was 0.892.The Cronbach coefficient scale factor was 0.879,and the Cronbach coefficient of each domain was between 0.486 and 0.956,indicating that the reliability of the scale is good.Because the questionnaire had conducted two rounds of expert consultation for item selection,and the background of experts covered clinical research and ethics,which can ensure that the questionnaire had good content validity.In construct validity,the study adopted exploratory factor analysis.Kaiser-Meyer-Olkin(KMO)of principal component factor analysis and Bartlett’s Sphericity Test(BST)showed that the data was suitable for factor analysis.Five common factors were extracted.The cumulative contribution rate of these five principal component factors was 70.831%.After orthogonal rotation,the first factor reflected the domain of comprehension and general evaluation,the second factor and the fifth factor mainly reflected the domain of voluntariness,the third factor mainly reflected communication satisfaction,and the fourth factors reflected the domain of completeness of information.Except for the domain of voluntariness,other domains were all concentrated,and the factor loadings were all above 0.5.It can be seen from the results that the items under the domain of voluntariness were scattered in different factors,which may be related to the inherent logical relationship among the items in the questionnaire.It also suggested that further adjustments can be made to the domain of voluntariness in the future.ConclusionIn this study,a questionnaire on the quality of informed consent for clinical trials of CM was formulated in accordance with the development program of the international guidance.Questionnaire evaluation showed that reliability and validity were relatively good.The items and language expression of the questionnaire can be further improved.It is expected to be used as an effective,reliable and simple tool for evaluation of the informed consent for trials of CM.