1. THE SCREENING OF CLINICAL RESEARCH PROJECTS Minggu penyelidikan perubatan dan kesihatan ke-15 UKM PROFESSOR DR. CHEAH FOOK CHOE PROFESSOR of PAEDIATRICS & NEONATOLOGY DEPARTMENT of PAEDIATRICS FACULTY of MEDICINE UKM MEDICAL CENTRE

2. RESEARCH SCREENING FORM REFER TO SPPI WEBSITE for this form Form is to be filled by the P.I. Verified by referee assigned by the UKM Research Ethics Committee

3. Elements to consider Highlights of matters including - Appropriateness of the research: 1) Ethical aspects because it involves human subjects 2) Soundness in terms of study approach and design 3) 4) 5) Time factor and investigator role Budgetary and other resource concerns Intellectual property and hospital involvement

4. Importance to clear first hurdle The successful approach Ask ONE simple question, something you encounter frequently enough in practice to make you consider/wonder : How, why or what??? Then search the literature for evidence, extensively enough so that the absence of any, justifies a new study for novel output It does not have to be groundbreaking, it may be something to substantiate a change of practice or be the foundation to establish a new guideline or SOP It could also be an audit of processes with a view of identifying risk factors

5. Pitfalls to avoid DO NOT be too ambitious The project should be pragmatic enough to be carried out successfully Within the set-up and available resources Patient recruitment and power of the study Time frame of the researcher as limited by the programme or funding

6. TITLE Short and sweet should reflect the main objective of the study and perhaps outcome Hanging type to enthuse readers The effects of showering on MRSA carriage Should not be a question type e.g. - -Does showering affectMRSA carriage? Statement type of conclusion of study - e.g. MRSA carriage is curbed by showering 10 times a day An unrelated title to the study is misleading and a sure-fire to have your proposal rejected/be revised

7. Related study Literature review to lead in to Importance of writing a concise background the justification of your research proposal Has any study been done before - novelty - high if not been done before yes, state the reported findings If - e.g. conflicting results or very old study in a different era could justify a new study with improved design Its not good to justify a study just because there is no Malaysian data and proceed to adopt some other s study methods to research the local context. The study output should be able to be used to modify clinical practice, improve outcomes or have some other targeted purposes NOT for the sake of just churning out local data or coming up with a study for a dissertation

8. Standard therapy Particularly important if you want to attempt another form of therapy Evaluation and comparative analysis Standard therapy is what is offered in the setting of the research site and not necessary what is recommended nationally/internationally The study may wish to compare with the recommended, use adjunct therapy, or a totally new method/drug for treatment

9. Screening is more meticulous If alternative therapy is studied What is the safety profile therapy Has there been sufficient produced Safeguard measures of this alternative evidence of safety Unlikely to approve high risk Phase 1 or 2 trials without a data monitoring committee (DMC)

10. Screening less stringent Auditing the centre performance to identify weaknesses or risk factors for quality improvement However, data such as this has implications for the set-up or centre Involvement of administrative heads in such research projects may be a bonus to avoid conflicts in publication later Non-inferiority trial or equivalence study of established therapies in a cost-benefit perspective No ethical issues (ref. lecture on ethics)

11. Objectives/hypotheses Straight to the point Overall big picture Main objective E.g. To look at risk factors for MRSA carriage health personnel Specific objectives: What risk factors e.g. behavioural ? MRSA carriage method by culture ? Health personnel in the surgical ward? nurses, doctors etc. ? in

12. Hypotheses That there is a difference or no difference (null) with a new therapeutic or diagnostic method That there is an increased risk in a study population from behaviour to disease The hypothesis is important to generate study population size: power and significance the

13. Study population Expect stringent screening including interview with ethics committee when the following at risk populations of study: - - - children pregnant women psychiatric illnesses Inclusion and exclusion of cases are necessary. Do not exclude a population that may benefit from the study just because they are disadvantaged e.g. follow-up more difficult etc. Exclusion criteria more important and exclusion is to remove conditions that likely to confound a study aim

14. Sample size Difference in outcomes The smaller the difference the larger the sample required Its not practical to study a small population with an unrealistically large difference in outcomes: for e.g. normally an SD of 5% difference, realistically (15%), not to inflate to You are not comparing 2-3 SD is practical e.g. 30% difference apples to oranges

15. Study design and site You have to know the condition you are studying well. You should do a survey of the rates of a certain disease you wish to study Look at the records and project how long you take to obtain the required numbers Collaborationwith other sites if necessary, BUT beware: Ethics approval from collaborative centre would Heterogeneity of processes and patient characteristics / demographics Intellectual property, MOU, MOU

16. Co-investigators Important to set out an agreement who are the investigators Investigators must be involved in the design and execution of the study and analysis of data as well as writing the results Share responsibility in the study publication Do not include names of people involved. Reputable journals are outcome and who are not hesitant when a small study have a long list of investigators and vice versa.

17. Co-investigators If trans-departmental or trans-disciplinaries, preferably each is represented Sign and document on publication policy Decide early who is the first author and the senior/corresponding author And intellectual property rights agreement especially if it involves a patentable or commercializable product

18. Materials transfer MTA Get legal units of research offices to appropriate reps/signatories to sign draft and About transboundary movements of samples for analysis Agreement should indicate the owner of the samples and permission must be granted before samples were used for other than the project objectives

19. DCA New drugs Use of a registered available new indication Approval to be granted first Prepare paperwork early Expect substantial time may get this ready and approved drug for another be necessary to

20. Flow chart & milestones/gantt chart In appendix or attachment Important to formulate this to provide a clear concise appreciation of the study in the big picture by the reviewer doing the screening Should include study population, exclusion criteria, expected groups of intervention/treatment/controls, outcomes and time frame Milestones and gantt chart for reviewer to screen if the time frame is reasonable for the study to be feasible

21. Budget Know your allowances/entitlements/grant limits Many big funds stipulate the different votes/categories with maximum spending in each Externally funded studies may need contractual obligations to be clearly stipulated University charges about 10% at least for overheads and admin charges fee Do not need to be too specific initially because upon approval, there will be another round of applications to tweak the budget if necessary

22. Questionnaires You cannot expect to create a questionnaire de novo before testing for validity (ref. lecture on validity etc.) Translated questionnaire need to be validated as well You should provide evidence that these are fulfilled in a pilot/prelim study Surveys of demographics do not need validation but if study involves questions about matters of subjectivity on a scale of more than yes/no then definitely necessary for validity testing Agreement and kappa is important if several investigators are involved in testing/collecting data through interaction at different sittings for reliability

23. Patient information sheet Follow format as provided by SPPI Basic information do not be overwhelmingly inclusive with sordid details of the study. Highlight the intervention. Explain the reason why you need to do the study. Concisely detail the medication/procedure and how variable this from standard therapy Essential to not withold information about the potential risk or side effects of the intervention is

24. Patient information sheet Basic appropriate language for the population targeted. Avoid medical jargon Essential to specify that: In a randomised get 50% chance the other. Once trial, if you are enrolled, you of getting one intervention or enrolled, no switching camps BUT can withdraw from study anytime. Stress that, routine care continues despite withdrawal. No repercussions. No kick-backs. Compensation within the boundaries of a true error or side effects or medical misdadventure

25. Consent Form Follow format and guideline from SPPI This is a LEGAL document. Be meticulous avoid spelling mistakes etc. Consent forms may be vetted also by pharma companies that include legality issues to adequately addressed This component is stringently screened especially by legal reps of any ethics committee be

26. Targets and planning Workout your schedule Get the necessary red-tape out of the way early esp. the agreements, signatories, paperwork to dept/agencies for approval Scrutinise the schedule for the Ethics Committee meetings and deliberation Choose a date that you are likely ready to submit meet this deadline Expect two weeks or so to get some feedback to May need amendments that demand further time for corrections and re-submissions

27. Finally Do it well on the first go Be well-prepared Avoid disappointing rejects or re-drafting for re-submission and presentation Save yourself time by investing in smart and calculated preparation of a reasonable, sound and pragmatically designed study

28. All the best for your research endeavours! Keep thinking of great ideas to research so as to improve the health of your patients! Minggu penyelidikan perubatan dan kesihatan ke-15 UKM (FC Cheah, 11Sep2013) The End