| Background:Patient compliance is critical in determining the efficacy of drugs in clinical trials.The reliability of results can be remarkably influenced by some participants who are unwilling to cooperate or drop out later.The poor compliance may result in essential data missing,which further affects the authenticity of results obtained from clinical trials.The patient compliance challenges in randomized controlled trials(RCTs)vary a lot from different types of diseases and populations.Purpose:To comprehensively explore the influencing factors and improvement strategies of patient compliance in clinical trials based on different diseases and populations in different research designs by literature research and qualitative research;To generate a theoretical system that assists the development of compliance screening tools and formulate improvement protocol.Using Traditional Chinese Medicine(TCM)oncology clinical trials as a carrier,this study carries out qualitative research to further verify the results from literature review,analyzes special influencing factors in TCM oncology clinical trials,and explores the opinions from researchers and patients.Study Methods:Study one:Relevant studies about investigating factors and potential strategies of compliance in clinical trials were searched in six databases(Pubmed,Cochrane,Embase,CNKI,VIP,WANFANG)and two clinical trial registries(Clinical Trials.gov and China Clinical Trial Registration Database)on November 29,2019.The types of included studies were not restricted.Literature screening and data extraction were carried out independently by two researchers and finally checked by two persons.The integration of data was a gradual and continuous process.The influencing factors and improvement strategies reviewed during data extraction process were continuously updated in the data extraction table.Results were presented mainly narratively,including visualization using word cloud and descriptive data.Study two:Relevant methodological studies about investigating factors and potential strategies were searched in three databases(CNKI,VIP,WANFANG)from January 2000 to December 2020.Literature screening and data extraction were independently performed by two researchers.Qualitative descriptions were used in the analysis of research data to explore the current status and differences between TCM and Western medicine patient compliance methodology research in clinical trials,and to find the shortcomings of existing domestic methodology research.Study three:Seven databases(Pubmed,Cochrane,Embase,PsycINFO,CNKI,Vip,Wanfang)were searched before December 2020.Qualitative studies exploring influencing factors and improvement strategies were separately included for analysis.CASP was used to assess the methodological quality of a single qualitative study,and CERQual was used to evaluate the integrated results of qualitative research conclusions.No research was excluded in the quality assessment.Open coding was finished by multiple readings of research results.On the basis of the initial coding,a wide range of topics were developed,and all text units were iteratively classified as one of the broad topics.Study four;A total of 25 patients and 9 researchers from TCM and Western medicine hospital in a Chinese medicine oncology clinical trial were conducted a pair of qualitative interviews.The interview outline was formulated based on the research results of Study one,and the interview design was conducted under the guidance of Study two and Study three.Interviewers were given rigorous interview training prior to Study four.The recording was transcribed and checked independently by two investigators.Thematic analysis and inductive analysis methods were used for data analysis.Results:Study one:From 188 included literatures,we identified 70 influencing factors(individual,environmental factors,diseases,study design,and researchers)and 42 improvement strategies(Study design,recruitment and informed consent,study implementation).Based on this,a system of influencing factors and strategies were constructed.The most common factors were age,gender,support from people,and trust in the trial,etc.Strategies that most frequently reported included expanding recruitment channels,carrying out education,flexible research time and location,and providing online reminders,etc.Women,adolescents,the elderly,and people with physical or mental illnesses may need more support from external conditions.For ethnic minorities,the culture,language,and the care of researchers played an important role in influencing compliance.For acute fatal diseases,the severity of the disease exerted an important influence.Trust in trials remarkably influenced acute non-fatal diseases.In chronic non-fatal and fatal diseases,the prolonged course of the disease may require more support from researchers and people around them.In addition,a full informed consent was essential in chronic fatal diseases.Study two:The results of 89 literatures demonstrated that methodological research had a great potential of patient compliance in clinical trials.The research still lacked enough attention and the researching focuses were scattered.Existing studies about compliance methodology still lagged far behind other studies.At present,most methodological studies did not highlight the impact on the compliance of a certain disease and the characteristics of the different clinical trials.Analyzing the factors and strategies from a holistic perspective can easily lead to a certain inapplicability.Compared with the compliance research of western medicine methodology,the emphasis on compliance in the research of TCM methodology was weaker.Study three:A total of 28 qualitative studies involving 11,151 patients and 224 researchers provided 151 first-order topics,36 second-order topics,and 8 third-order topics.Although the factors and strategies mentioned in different populations and diseases varied a lot,we believed that these factors and strategies could be classified into broader,more inclusive rules and commonality.These factors may be related to individual(e.g.,fitness,routine schedule,emergencies,psychology),diseases(e.g.,the severity of the disease),environmental factors(e.g.,social environment,humanistic environment,and transportation),research designs(e.g.,study protocol,interventions,compensation),or researchers(e.g.,researcher’s attitude and ability).Strategies were divided based on the sequence of the study,including three stages of study design,recruitment and informed consent,and follow-up.It is generally believed that the design of the research plan from the perspective of the participants was the basis for the stage of study design.In the recruitment and informed consent phase,researchers needed to fully explain about the trial to the participants.Adequate explanation allowed participants to fully consider the advantages and limitations of participating in clinical trials,so as to make a reasonable choice that mostly fitted their true ideas.During the follow-up phase,adequate communication and timely contact were key strategies to improve participant compliance.The influencing factors and improvement strategies of synthesis of qualitative research were basically similar to the results of the previous scoping review.The level of evidence based on influencing factors and improvement measures ranged from moderate to low,and the influencing factors of moderate evidence mainly included the attitude of researchers,reimbursements,study protocol,convenience to the research center,etc.In addition,the improvement strategies suggested by the moderate evidence included improving the attitude and technique of researchers,compensation and encouragement,improving the methods and forms of follow-up,timely feedback,etc.Study four:A total of 9 researchers and 25 patients in clinical trials were thoroughly interviewed.Among the influencing factors,63 first-order topics and 20 second-order topics that belonged to 5 third-order topics(individual,environmental factors,diseases,study design,and researchers)were found.Both patients and researchers believed that personal values,challenges to time,stigma,and the protocol of intervention were the main factors affecting patient compliance in clinical trials.In particular,adverse events like nausea and vomiting during chemotherapy,medical history of chemotherapy,and COVID-19 may be unique factors in this TCM oncology clinical trials.In the improvement strategies,a total of 24 first-order topics and 7 second-order topics were found,which were classified into 3 stages(Study design,recruitment and informed consent,study implementation).The interviewees agreed that simplifying the design of protocol,fully informed consent,timely reminders and feedback were important strategies for improving compliance.Determining the treatment based on the differentiation of symptoms ’and screening subjects based on survival may be unique strategies in this TCM oncology clinical trial.The potential factors and improvement strategies provided by researchers and patients may be different.The results of Study three and Study four verified and further enriched the system of influencing factors and improvement strategies in Study one.The results of the four studies altogether constituted a screening table involving 52 elements for predicting patient compliance,and a list of 93 strategies to improve it.Conclusion:Our research comprehensively and systematically summarizes the influencing factors and improvement strategies of patient compliance in clinical trials from different perspectives.Our study explores the influencing factors and improvement strategies of patient compliance in clinical trials in different diseases and populations from different studies,and constructs a system of the influencing factors and improvement strategies of compliance.Our suty analyzes the current status of the TCM and western medicine methodological research on patient compliance is still flawed and explored the special influencing factors and improvement strategies of this tumor clinical trial of TCM.In the future,more clinical studies can improving patient compliance based on the screening table for predicting compliance and the list of improvement strategies provided in our research. |
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