1. Adequacy of Ethical Review and Informed Consent Documents in Investigations Submitted For Funding To The Eastern Mediterranean Region of the World Health Organization Alaa AbouZeid 1, Mohammad Afzal 1, Henry Silverman 2 1 WHO, Eastern Mediterranean Regional Office, Research Policy and Cooperation Unit, Cairo. Egypt 2 University of Maryland School of Medicine, Baltimore, Maryland, USA Funding: Supported in part by FIC/NIH5 R25 TW007090-02

2. Background Research in developing countries has grown enormously during the last decade. Commentators have expressed concern that: –many of these countries lack effective ethics review systems –the concept of informed consent is imperfectly realized. The current literature only describes in qualitative terms the status of ethics review of research and the regard for informed consent in the countries of the Eastern Mediterranean Region. A thorough situation analysis of the status of health research ethics in the Eastern Mediterranean Region would help policy makers enhance efforts to increase research ethics capacity.

3. Objectives To determine the extent to which ethics review is obtained for health research. To determine the extent to which there is an intent to obtain informed consent for health research. To determine the adequacy of informed consent forms used in health research.

4. Methods Setting: Applicants from 12 countries submitted proposals (2006) to the –EMRO/WHO Grant schemes in priority areas of public health –EMRO-COMSTECH Grant schemes in applied biotechnology and genomics. Data Measurements: Analysis of information stated in the proposals regarding the obtainment of ethics review and the intent to obtain informed consent. Analysis of elements of informed consent forms in submitted forms

5. Methods We developed a checklist tool listing the basic elements of informed consent (IC). A scale of 1-5 was used to rate each element. –A score of 1 indicated presence of the element with complete and understandable information –A score of 2-4 indicated presence of the element, but with inadequate information –A score of 5 indicated absence of the element. Two authors (AB-Z and MA) made an independent assessment of the elements; the third author (HJS) compared the assessments and subsequently merged the two assessments to produce a final rating.

6. Table 1. Research Proposals submitted for EMRO/COMSTECH Grants (2006) n = 144 Types of Researches Submittedn% Human Subject Research*10672.2 + Intervention Study (non-drug)3121.5 Collection of biological tissues5437.5 Interview/Questionnaire9868.1 Archived data collection2618.1 RESULTS * Proposals contained multiple types of research methods + % of total submissions (n = 144)

7. Table 2. Ethical Clearance and Informed Consent for the Human Subject Research Proposals (n=106) Ethical Considerationn% Ethical Clearance obtained upon submission4441.5 Informed Consent will be obtained6359.4 Informed Consent will not be obtained3028.8 No mention regarding obtaining informed consent10 9.6 Informed Consent Document Provided4542.5 RESULTS

8. Country Human Subject Researchers Number of Applications n Ethical Clearance (%) Informed Consent (%) Confidentiality (%) A42526283 B19423774 C19248495 D74371100 E52080100 F300 G367 33 H1100 I10 J0000 K47550100 L20067 Total10642.559.485.8 Country Data

9. Table 3. Availability and adequacy of information in Informed Consent Form Documents (n = 45) Informed Consent ElementAdequateInadequateAbsent Description of the Research Purpose Statement that the study involves research Expected duration of subject’s participation Description of procedures 22 (49%) 17 (38%) 14 (31%) 20 (44%) 16 (36%) 12 (27%) 2 (4%) 21 (47%) 7 (16%) 16 (36%) 29 (64%) 4 (9%) Description of risks11 (34%)10 (22%)24 (53%) Description of benefits To the subject To society 19 (42%) 10 (22%) 4 (9%) 8 (18%) 22 (29%) 27 (60%) Disclosure of Alternatives10 (22%)0 (0%) 35 (78%) Assurances of Confidentiality23 (51%)8 (18%)14 (31%) Availability of medical care for research injury 0 (0%) 45 (100%) Contact Information Questions about the research Questions about subjects’ rights or complaints Questions about research injury 16 (36%) 2 (4%) 0 (0%) 7 (16%) 1 (2%) 0 (0%) 22 (49%) 42 (93%) 45 (100%) Voluntariness of participation27 (60%)0 (0%)18 (40%) Ability to withdraw32 (71%)0 (0%)13 (29%) Name of investigator and institutional affiliation 16 (36%)10 (22%)19 (42%)

10. Number of Missing Elements

11. Discussion Many investigators (~45%) did not obtain ethical approval for their research proposals prior to submission. Many investigators (~30%) did not intend to obtain informed consent Of those investigators who realized the value of informed consent, only two-thirds submitted a written document. A large number of basic elements of informed consent forms were absent or inadequately describe in many informed consent forms.

12. Half Full or Half Empty?

13. What is the Benchmark? Studies from Western countries have also demonstrated inadequacy of informed consent documents –Advisory Committee on Human Radiation Experiments (1950s) –Office for Human Research Protections (OHRP) –NIH sponsored study regarding treatment of respiratory failure (1990s) Silverman, et.al Crit Care Med. 2001

14. Recommendations Awareness regarding the necessity of ethical review and need for informed consent needs to be enhanced among many investigators in the Eastern Mediterranean Region. Increased efforts are needed to enhance the knowledge regarding information needed for a valid informed consent Educational training programs should further be developed to enhance research ethics capacity.