Improving Informed Consent Comprehension and

Improving Informed Consent Comprehension and Quality of Informed Consent Process in Low Literacy and Resource Limited Setting: Cluster Randomized Clinical Trial.

CONTRIBUTING AUTHORS Serebe Abay*, [email protected] Technology Transfer and Research Translation Ethiopian Public Health Institute, Addis Ababa, Ethiopia Adamu Addissie, [email protected] Brighton and Sussex Medical School, Brighton, UK; and Addis Ababa University, Addis Ababa, Ethiopia Gail Davey, [email protected] Brighton and Sussex Medical School, Brighton, UK

Yeweyenhareg Feleke, [email protected] Addis Ababa University, Addis Ababa, Ethiopia Melanie Newport, [email protected] Brighton and Sussex Medical School, Brighton, UK Bobbie Farsides, [email protected] Brighton and Sussex Medical School, Brighton, UK Thomas Addissie, [email protected] Addis Ababa University, Addis Ababa, Ethiopia *correspondent author

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FOREWORD With the advancement of science and technology, increased disease burden, and expansion of higher education and research institutions, the number of research conducted increased more than ever in the past. Although research has vital role for the wellbeing of the public and the globe, in line with this the issue of biomedical ethics need to be advanced to safeguard the dignity, rights, safety, and welfare of all actual or potential research participants and/or communities.

The aim of this study is to introduce researchers with an innovative tool to improve informed consent comprehension and quality of consent process in research involving human participant. It mainly focuses on research involving participants from low literacy and limited recourse setting. In this study, we have used the fundamental concepts and principles of the Belmont Report, Council for International Organizations of Medical Science (CIOMS), Declaration of Helsinki and other local research ethics guide lines. The authors would like to acknowledge the data collection team and supervisors for their significant contribution to accomplish this work. We are very thankful to Wellcome Trust for the financial support and International Orthodox Christian Charities (IOCC) podoconiosis research group for the financial administration support.

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ABBREVIATIONS AAU  Addis Ababa University AIDS  Acquired Immune Deficiency Syndrome ANC  Antenatal Care AOR  Adjusted Odds Ratio BICEP  Brief Informed Consent Evaluation Protocol BIQ  Brief Investigator Questionnaire CI  Confidence Interval CS  Compression Score DICCT  Deaconess Informed Consent Comprehension Test ERCs  Ethics Review Committees ESTC  Ethiopian Science and Technology Commission FGD  Focused Group Discussion FMHACA  Food, Medicine and Health Administration and Control Authority HIV  Human Immunodeficiency Virus HPV  Human Papilloma Virus HRRC  Health Research Review Committee HST  Health Science and Technology ICC  Informed Consent Comprehension IDI  In-depth Interview IERCs  Institutional Ethics Review Committees IICF  Improved Informed Consent Form II

IRB  Institutional Review Board MICCA  Modular Informed Consent Comprehension Assessment MoST  Ministry of Science and Technology NERC  National Ethics Review Committee NHRERC  National Health Research Ethics Review Committee NHSTC  National Health Science and Technology Council OR  Odds Ratio QuIC  Quality of Informed Consent REA  Rapid Ethical Assessment RERCs  Regional Ethics Review Committees RHB  Regional Health Bureau SICF  Standard Informed Consent Form

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TABLE OF CONTENT FOREWORD..............................................................................................................................................................II ABBREVIATIONS ....................................................................................................................................................II TABLE OF CONTENT ........................................................................................................................................... IV LIST OF TABLES ................................................................................................................................................... VI LIST OF FIGURES ................................................................................................................................................. VII LIST OF ANNEXES .............................................................................................................................................. VIII ABSTRACT ............................................................................................................................................................. IX 1.

2.

3.

4.

INTRODUCTION ..............................................................................................................................................1 1.1.

Rapid Ethical Appraisal..............................................................................................................................2

1.2.

Statement of the Problem ...........................................................................................................................3

1.3.

Justification of the Study ............................................................................................................................3

LITERATURE REVIEW ...................................................................................................................................4 2.1.

Ethics of Research in Developing World ...................................................................................................4

2.2.

Research Ethics in Ethiopia ........................................................................................................................7

2.3.

Informed Consent Comprehension Test .....................................................................................................9

2.4.

Findings about Informed Consent Comprehension Studies .................................................................... 10

OBJECTIVES.................................................................................................................................................. 13 3.1.

General Objective: ................................................................................................................................... 13

3.2.

Specific Objectives: ................................................................................................................................. 13

METHODS AND MATERIALS .................................................................................................................... 14 4.1.

Study Area ............................................................................................................................................... 14

4.2.

Study Design ........................................................................................................................................... 14

4.3.

Population ............................................................................................................................................... 15

4.3.1.

Source population ............................................................................................................................ 15

4.3.2.

Study population .............................................................................................................................. 15

4.3.3.

Inclusion and exclusion criteria ....................................................................................................... 15

4.5.

Sampling Procedure................................................................................................................................. 16

4.6.

Study Variables ....................................................................................................................................... 16

4.7.

Data Collection and Instruments ............................................................................................................. 17

Phase I- Qualitative community based rapid ethical assessment ....................................................................... 17

IV

4.7.1.

Qualitative Data ............................................................................................................................... 17

4.7.2.

Quantitative data .............................................................................................................................. 19

4.7.3.

Data quality assurance ..................................................................................................................... 19

4.8.

Operational Definition ............................................................................................................................. 21

4.9.

Data Processing and Analysis .................................................................................................................. 22

4.9.1.

Measurement ................................................................................................................................... 22

4.9.2.

Informed Consent Form................................................................................................................... 23

4.10. 5.

Ethical Consideration ......................................................................................................................... 24

RESULT ........................................................................................................................................................... 26 Phase I- Qualitative community based rapid ethical assessment .................................................................. 26 Socio-demographic characteristics of participants .......................................................................................... 26 Understanding between health research and treatment ................................................................................... 26 Awareness of and local terminologies for cervical cancer .............................................................................. 27 Information dissemination and communication channel ................................................................................. 28 Consent seeking procedure .............................................................................................................................. 29 Sample collection technique ............................................................................................................................ 30 Gender dynamics surrounding decision making.............................................................................................. 31 Participant selection......................................................................................................................................... 32 Expectations from participation....................................................................................................................... 33 Phase II- Quantitative: Cluster randomized interventional study ....................................................................... 35 Socio- demographic and economic characteristics of the study participants................................................. 35 Recruitment rate, compliance rate and lost rate among participants enrolled with modified and standard consent form. ................................................................................................................................................... 37 Informed consent comprehension assessment ................................................................................................. 38 Quality of informed consent process on participant perspective ..................................................................... 42 Sources to gather health information ............................................................................................................... 43

DISCUSSION............................................................................................................................................................ 45 CONCLUSION .......................................................................................................................................................... 55 REFERENCE .............................................................................................................................................................. 56 ANNEXES .............................................................................................................................................................. 63

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LIST OF TABLES Table 1 : Comparison of modified and standard consent forms used to enroll participants in the intervention and control groups, respectively July 2013 .................................................................................................................... 24 Table 2: Socio-demographic and economic characteristics of respondents in Wukiro kilte-awulaelo and Hintalwajirat districts, Tigray region, July 2013 .............................................................................................................. 36 Table 3 : Comparing comprehension mean score among the intervention and control groups in wukiro kilteawulaelo and Hintal-wajirat district, Tigray region, July 2013 ............................................................................. 38 Table 4 : Level of informed consent comprehension in the intervention and control groups district wukiro kilteawulaelo and Hintal-wajirat, Tigray region, July 2013 .......................................................................................... 39 Table 5 : Mean score of consent components among participants of the two groups in district wukiro kilteawulaelo and Hintal-wajirat, Tigray region, July 2013 .......................................................................................... 40 Table 6 : Variables associated with comprehension status among study participants in wukiro kilte-awulaelo and Hintalo-wajirat district, Tigray, July2013 .............................................................................................................. 41 Table 7 : Comparison of mean score of quality of informed consent process on participant perspective among the two groups, July 2013.............................................................................................................................................. 43 Table 8 : Source of health information for the study participant in district wukiro kilte-awulaelo and Hintalwajirat, Tigray region, July 2013 ............................................................................................................................ 44

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LIST OF FIGURES Figure 1 : Conceptual frame work of factors affecting the Informed Consent Comprehension and quality of consent process in biomedical research in developing countries ........................................................................... 12 Figure 2 : Educational level of participants of the two groups in wukiro kilte-awulaelo and Hintal-wajirat districts, Tigray region, July 2013 .......................................................................................................................... 35 Figure 3: The recruitment rate, retention rate and lost rate among participants in wukiro kilte-awulaelo and Hintal-wajirat district, Tigray region, July 2013 .................................................................................................... 37

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LIST OF ANNEXES Annex I : Schematic presentation of the sampling. ................................................................................................. 63 Annex II : Interview guiding questionnaire for IDI and FGD used for Rapid Ethical Assessment ........................ 64 Annex III : Narrative Explanations used in the intervention group ........................................................................ 65 Annex IV : English version data collection format: Informed consent comprehension and quality of consent process assessment .................................................................................................................................................. 66 Annex V : Table showing the type of question (superscripts numbers) and their correct answer (given in brackets) used for comprehension and quality of consent process assessment ...................................................................... 73

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ABSTRACT Background: Informed consent is a key component of biomedical research involving human participants. However, obtaining informed consent is challenging in low literacy and resource limited settings. Potential research participants should be assisted with interventions to improve their comprehension. Application of Rapid Ethical Assessments(REA) to improve informed consent process is increasingly considered useful. REA is an intervention developed to contextualize consent processes in low-income setting. This study aimed to assess the effects of Rapid Ethical Assessment on comprehension level, retention rate and quality of the informed consent process. Methods: Institutional based interventional study was employed among pregnant women of age 18-45 years in Wukiro kilte-awulaelo and Hintalo-wajirat districts, Northern Ethiopia, from July 8 to August 20, 2013. This study had two phases: A first phase qualitative community based rapid ethical assessment followed by a second phase facility based cluster randomized interventional study. The qualitative rapid ethnographic assessment study was done among key informants in the intervention site concerning biomedical research, cervical cancer, communication channel, socio-cultural dynamics, gender dynamics in decision making, sample collection and how to find informed volunteer participants with fully understanding for the parent study. We did In-depth Interviews(IDIs) and Focused Group Discussions (FGDs) with key informants. Tape recorded data were transcribed in Tigrigna and then translated into English. Data were categorized and thematically analyzed using open coding. Then informed consent content and process was improved based on the REA findings. A total of 300 healthy pregnant women who were eligible for the parent study were included in the interventional study. Using 1:1 ratio, 150 participants were allocated for each group. The intervention group received the Improved Informed Consent Form(IICF) and the controls received the Standard Informed Consent Form(SICF). After two weeks of initial consent for the parents study both groups were assessed for informed consent comprehension level and quality of consent process by using Modular Informed Consent Comprehension Assessment (MICCA) and Quality of Informed Consent (QuIC) process assessment tools, respectively. Regression analysis was done for comparative analysis and a risk ratio with 95% confidence intervals was used to assess associations between dependent and independent variables. Multivariate logistic regression model was used to control for confounders and to adjust measures of association.

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Result: The Rapid Ethical Assessment study revealed a number of socio-cultural issues concerning the proposed study. Low community awareness about cervical cancer, misunderstanding of health research, and low awareness of participant rights were documented. Giving a vaginal sample for testing was considered to be highly embarrassing, whereas giving a blood sample made participants worry that they might be given a result without the possibility of treatment. Verbal consent was preferred to written consent for the proposed study. The initial recruitment rate to participate in the parent study for the intervention and control groups were 88.7% and 80.7%, respectively. The compliance rate to show follow-up 12 days after initial consent were 85.7% for the intervention group and 70.3% for control group. Overall mean score of Informed Consent Comprehension(ICC) for the intervention and control groups were 73.1% and 45.2%, respectively. Mean difference in comprehension score was 27.9% (P