Makanani, the principal investigator at the Blantyre site for allowing me access to the study and for the support. Mfutso-Bengo and colleagues at Center for Bioethics, University of Malawi- for the support (Francis, Vin, Thandie, James, Judith).
INTRODUCTION 130
DESCRIPTION OF THE MICROBICIDE TRIAL (HPTN035 STUDY) 138
FINDINGS RELATING TO THE MICROBICIDE STUDY PARTICIPANTS
FINDINGS RELATED TO UNDERSTANDING OF RANDOMISATION 212
SUMMARY 236
DEMOGRAPHIC CHARACTERISTICS OF RESPONDENTS WHO PARTICIPATED IN THE PILOT INTERVENTION
FINDINGS ON THE EFFECTIVENESS OF THE INTERVENTION 266
OBSERVATIONS DURING THE INTERVENTION PHASE 285
DISCUSSIONS ON PREMISE 4 - INTERVENTION TO IMPROVE UNDERSTANDING
CHALLENGES FACED DURING THE IMPLEMENTATION OF THE STUDY
CONCLUSIONS : IMPLICATION OF FINDINGS FOR INFORMED CONSENT
RECOMMENDATIONS 319
LIST OF TABLES
278 Table 9.18 Statistics of intervention and non-intervention groups before intervention 279 Table 9.19 Statistics of intervention and non-intervention groups after intervention 280 Table 9.20 Independent samples t-test results before intervention 281 Table 9.21 Independent samples t-test results after intervention 2822 Intersection table9. Intervention and attitude towards the use of placebo 283.
LIST OF APPENDICES
A study of trial participants’ understanding and attitudes towards randomisation, double-blinding and placebo use, and a pilot intervention in
INTRODUCTION
- BACKGROUND
- STATEMENT OF THE RESEARCH PROBLEM
- RATIONALE FOR THE STUDY
- MAIN PREMISES AND ASSUMPTIONS OF THE STUDY
- RESEARCH APPROACH OF DISSERTATION
- CONTRIBUTION OF THESIS
- OUTLINE OF THESIS
In addressing these issues, there is a need to empirically investigate research participants' understanding of the concepts of double blinding. Given the above, this study aimed to explore the research participants' understanding of the above concepts.
LITERATURE REVIEW
INTRODUCTION
The eighth section reviews and discusses previous studies that assessed trial participants from other studies conducted in developed countries. The ninth section reviews and discusses studies conducted in developing countries to assess trial participants' understanding.
INFORMED CONSENT AND THE NEED FOR TRIAL PARTICIPANTS’ UNDERSTANDING
A statement that the specific treatment or procedure may entail risks for the subject (or for the embryo or fetus, if the subject is or may become pregnant) that are currently unforeseeable. Yet ethically valid informed consent requires more than just disclosure of the eight pieces of information (Flory & Emanuel, 2004).
THE ETHICS OF RANDOMISATION, PLACEBO USE AND DOUBLE-BLINDING
The use of placebos was also widely discussed during the revision of the Declaration of Helsinki in 2000. Several studies reported that trial participants, despite being aware of the use of procedures such as randomization, had difficulty understanding and appreciating these concepts.
THE ETHICS OF HIV PREVENTION TRIALS
Who should be responsible for the treatment of those individuals who become infected during the course of the microcide trial. UNAIDS (2000) recommends that risk reduction measures such as counselling, condom promotion and training in condom negotiation skills should be part of HIV prevention trials to ensure that infection risk behaviors do not increase beyond those reported at registration.
ASSESSING HIV VACCINE TRIAL PARTICIPANTS’
UNDERSTANDING
ASSESSING MICROBICIDE TRIAL PARTICIPANTS’
However, focus group discussions at the end of the trial suggested that some women still did not understand the blinding process (Kilmarx et al., 2001). The present section has highlighted some of the debates in the field of microbicide trials.
ASSESSING PERSONS WITH LIMITED DECISION MAKING CAPACITIES
One of the studies focusing on patients with limited decision-making capacity was conducted by Baskin, Morris, Ahronheim, Meier, and Morrison (1998). quantitative study in the USA to identify barriers to informed consent for patients with. In the study, the MacArthur Competence Assessment instrument was administered to 27 patients and 24 members (normal controls) of the same age as the patients selected from the community. The questionnaire used in the study included various aspects of trial information, but the authors did not report the analysis of the individual responses.
STUDIES ASSESSING UNDERSTANDING OF CANCER TRIAL PARTICIPANTS
They recommended that informed consent should be strengthened by improving the readability of informed consent forms. A similar study which focused on the readability and length of informed consent forms was conducted by Sharp (2004). The results showed that participants had a good overall understanding of the elements of informed consent as well as the trials for which they were enrolled.
STUDIES CONDUCTED IN DEVELOPED COUNTRIES TO ASSESS UNDERSTANDING OF TRIAL PARTICIPANTS
One of the earliest studies in the new millennium was conducted by Mason and Almark (2000). They suggest that informed consent researchers need the cooperation of the investigators they want to study. The majority of the 32 participants were aware of the key elements of informed consent; information, understanding, competence and decision-making.
STUDIES CONDUCTED IN DEVELOPING COUNTRIES TO ASSESS TRIAL PARTICIPANTS’ UNDERSTANDING
Informed consent in the HIV study was divided into two parts: a group discussion led by trained study nurses, followed by individual interviews. About 21 percent of respondents found the discussion more useful than the informed consent form. Eighty-four percent of respondents acknowledged that measures of understanding should be included in informed consent processes.
STUDIES CONDUCTED IN AFRICA TO ASSESS TRIAL PARTICIPANTS’ UNDERSTANDING
The findings also showed that mothers agreed to participate in the study not on the basis of relevant information but on the basis of trusting the researchers. The questionnaire covered aspects of the information disclosed in the trial leaflet. The authors found that 85 percent of respondents knew that the purpose of the research was to test a new drug.
STUDIES AIMED AT IMPROVING TRIAL PARTICIPANTS’
Studies involving augmenting the informed consent process with a videotape showed considerable promise. The authors' recommendations were not evaluated as their research was only aimed at eliciting the children's views on how informed consent could be improved. Some of the weaknesses of this study include the fact that the same information found in informed consent documents was repackaged and supplemented with visual aids.
SUMMARY OF LITERATURE REVIEW
Some of the tests that researchers have used to assess comprehension are better suited for assessing short-term recall, which is not an adequate indicator of comprehension. The literature review also shows that in some studies assessing comprehension, researchers did not develop conceptual and operational definitions of comprehension prior to the assessment. Some of the tools that have been used have been deficient in terms of validity and reliability, administration standardization, scoring, and interpretation.
CONCEPTUAL FRAMEWORK
- INTRODUCTION
- FADEN AND BEAUCHAMP’S PYCHOSOCIAL SCHEMA
- MEERWEIN MODEL OF THE INFORMING PROCESS
- TAXONOMY FOR ANALYSING UNDERSTANDING OF CLINICAL TRIAL CONCEPTS
- SUMMARY
Based on the Psychosocial Schema and the Meerwein model of the process of information, a conceptual framework was developed for this study that incorporates aspects of both. The information stage requires sufficient time from the potential participant to process the information without coercion. Adapted from Bhutta, 2004: The framework combines Faden and Beauchamp's picosocial scheme and the Meerwein model of the information process.
STUDY AIM AND OBJECTIVES
- INTRODUCTION
- MAIN STUDY AIM
- SPECIFIC OBJECTIVES
- RESEARCH QUESTIONS
- STUDY HYPOTHESES
- SCOPING THE BOUNDARIES OF THE STUDY
- SUMMARY
Are the participants in the study aware that randomization, double-blindness and placebo use are part of the study? Are the participants in the study aware of the reasons why randomization, double-blindness and placebos are used in the study? 12.Are the participants in the study aware of the personal implications of randomization, double-blindness and placebo use?
RESEARCH METHODOLOGY
INTRODUCTION
STUDY DESIGN
The reason or purpose of the study was, from a broad perspective, to evaluate the participants in the trial. In turn, the in-depth interviews and focus group discussions used in Phase 1 attempted to capture trial participants' perceptions and experiences of the microbicide trial procedures in the. In phase 2, the design and development of the intervention described in this thesis was based more on a qualitative approach, while the evaluation of the intervention was based more on a quantitative approach.
STUDY AREA
Cross-sectional research is often used in descriptive studies because it provides a snapshot or a quick look at the phenomenon being studied at a specific time in a specific place. Ethnic groups consist of Chewa, Nyanja, Tumbuka, Yao, Lomwe, Sena, Tonga, Ngoni, Ngonde, Asians and Europeans. In terms of religion, Christians form the majority of the population (79.9 percent), followed by Muslims (12.8 percent), the rest 3 percent and nil 4.3 percent (National Statistical Office Malawi, 2004).
STUDY SITES
- University of North Carolina (UNC) Project
- Johns Hopkins Research Centre
The UNC project has a collaborative relationship with the Ministry of Health and the College of Medicine (COM) at the University of Malawi based in Blantyre, and also works in partnership with several international organisations. The Johns Hopkins Research Center is based at Queen Elizabeth Central Hospital in Blantyre and is a collaboration between the Bloomberg School of Public Health at Johns Hopkins University in Maryland, USA and the College of Medicine at the University of Malawi. Queen Elizabeth Hospital is located in central Blantyre and is one of the two main referrals.
STUDY POPULATION
DESCRIPTION OF THE MICROBICIDE TRIAL (HPTN035 STUDY)
The Phase II portion of the study involved intensive safety evaluations among the first 799 women enrolled. The study was a four-arm, multi-site, randomized controlled trial comparing BufferGel and 0.5% PRO 2000/5 Gel (P) with a placebo gel and no gel. The study demonstrated for the first time the promise of a vaginal microbicide gel for the prevention of HIV infection in women.
STUDY PERIOD
SAMPLE SIZE AND SAMPLING PROCEDURE
Expected frequency of good scores: 50 percent (This value is recommended for dichotomous variables as it results in the maximization of variance and produces the maximum sample size – Bartlett, Kotrlik & Higgins, 2001). The sample size obtained using the above formulas was confirmed using the Macorr sample size calculator, a web-based sample size calculation tool. Eligible staff were then invited to participate in the study and provided with a small slip to complete and return to the Research Assistant with their name, contact information and time when they might be available for an interview.
RESEARCH QUESTIONS AND METHODS
- Recruitment methods and sampling
- Information Disclosure
- Research Participants’ Understanding
- Intervention to Improve Understanding
Are trial participants aware of the personal implications of randomisation, double-blind and placebo. What are the opinions of the trial participants about randomization, double-blind and the use of placebo. Trial participants are aware of the purpose of double-blind, randomization, and the use of placebo in research.
DATA COLLECTION METHODS AND TOOLS
- Document Review: Document review served as a very valuable source of information as it provided background information about the informed consent processes and procedures
- Structured Interviews: The structured questionnaire was identified as the most suitable instrument for collecting data on trial participants’ understanding, given that the main aim of
- The Development of the Structured Questionnaire
- In-depth Interviews: In-depth interviews were held with two study nurses at each site
- Focus Group Discussions (FGD): Two FGDs were held with a total of 18 microbicide trial participants who had not participated in the individual interviews. The FGDs were used to
- Observations: During the process of data collection, some unstructured observations of facility layout, interactions with trial participants and informed consent processes were made
The questionnaire included several comprehension questions related to each of the three concepts under study. FGDs also provided an opportunity to clarify answers that remained unclear during the administration of the structured questionnaire. Observations are based on direct eye and ear evidence to witness events first hand.
VALIDITY AND RELIABILITY IN DATA COLLECTION
This also led to the removal of some questions that were not clear and some that were repetitive. Pilot Testing of Tools – The questionnaire, in-depth interview guide and FGD guide were pilot tested in Blantyre prior to actual data collection. Testing was done to ensure that the wording, sequence of questions, and types of questions used in the instruments were related to the research questions and to the study as a whole.
STUDY PROCEDURES
Data analysis – During the data analysis phase, subjective interpretation of data was avoided and coding of open questions was done carefully. The role of the second coder was to confirm the coding by the first. This was done to ensure consistency in the meaning obtained from the responses.
OPERATIONAL AND STATISTICAL DEFINITIONS
- General Definition of “Understanding”
- Operational Definition of “Understanding”
- Statistical Definition
Awareness of the implications of their participation regarding protection against infection by the tested product. It is believed that the presence of the above elements would lead to making an informed decision about research, taking into account the three procedures of research. The treatment offered is not intended to treat the participant, but to test the usability of the product being tested.
DATA MANAGEMENT
A paired t-test was also done to check whether the means of the respondents before the intervention and after the intervention differ from each other. Transcribed text of each of the interviews and responses carefully transcribed verbatim. Some of the qualitative findings were used to verify or support some of the quantitative findings obtained through the structured interviews with 203 participants.
ETHICAL CONSIDERATIONS
Four of the seven women who refused to take part in the first phase said they feared their partners would discover they were taking part in the microbicide trial if they were away from home for a long time. Two of the three women who refused to participate in the intervention phase indicated that they could not participate in the second phase due to other commitments. Participants were assured that their names would not be used in reports of the study.
SUMMARY
All study materials were kept secure and could only be accessed by the researcher, statistician and other staff associated with the study. The paper documents were kept in a locked steel cabinet and the informed consent forms were stored separately from the questionnaires in order to avoid linking the two documents. Reimbursements: Women who participated in both phases of the study were reimbursed for transportation using the standard rate applicable in both countries.
FINDINGS FROM THE MAIN PHASE OF THE STUDY
INTRODUCTION
FINDINGS FROM DOCUMENT REVIEW
- Study Protocol
- Informed Consent Forms
The importance of participants in all four study groups to the success of the study. Therefore, the study staff will remind you of the importance of using condoms to protect against HIV. Therefore, the study staff will remind you of the importance of using condoms to protect against HIV.
