From the idea to the project: Role of the Research Review Committee

1. From the idea to the project: Role of the Research Review Committee Lauren B. Strober, Ph.D. Neuropsychology & Neuroscience Laboratory 19 September 2012

2. FIRST STEPS • PLAN AHEAD!!! • Find out the schedule of when the RCC meets. • Access the IRB website at http://kesslerfoundation.org/researchcenter/irb/to obtain the RRC meeting schedule or contact Malica Dock, IRB Coordinator at mdock@kesslerfoundation.org • Plan, on average, 3 or possibly more months from the time you submit to be approved. • PLAN!!! (Prove me wrong)

3. How an IDEA becomes a STUDY • You have emailed or spoken to Malica Dock and she is expecting your proposal. • Decipher what type of review your study needs • Exempt • Expedited • Full

4. STUDY REVIEW CATEGORIES

5. SUBMISSION PROCESS FULL IRB REVIEW EXEMPT OR EXPEDITED REVIEW IF FUNDED, STUDY DOES NOT NEED TO GO TO THE RCC AND WILL PROCEED DIRECTLY TO IRB FOR REVIEW Original & 14 copies of research proposal sent to RRC & IRB Electronic copy of the entire packet sent Original & 1 copy of research protocol sent to RRC & IRB Electronic copy of the entire packet sent

6. What You Must Include in an IRB application • Cover letter • IRB Initial application • Research Proposal Outline/Protocol • HIPAA/NOPP forms OR Waiver • Consent forms • CITI instructions – all study team members certifications should be submitted • If funded, copy of grant

7. What You Must Include in an IRB application • Cover letter • IRB Initial application • Research Proposal Outline/Protocol • HIPAA/NOPP forms OR Waiver • Consent forms • CITI instructions – all study team members certifications should be submitted • If funded, copy of grant

8. Cover Letter – Sample 1 To the IRB: Enclosed please find one original and 14 copies of our IRB proposal entitled Evaluation of the effectiveness and outcomes of a comprehensive, outpatient cognitive rehabilitation program.The study procedures described within are part of the Cognitive Rehabilitation Program (CRP) of the Kessler Institute for Rehabilitation. Dr. Tremaine and I have long discussed examining the effectiveness and outcomes associated with the program and are seeking IRB approval for such. Please note that this study is not a proposed, new intervention, but is an examination of what is considered standard clinical care for individuals enrolled in the CRP and is what participants will undergo regardless of their participation in the study. We are primarily asking them to allow us to use their de-identified data for research purposes. The only exception to this is the control participants, who will be asked to complete a series of questionnaires and brief cognitive test battery, despite not being enrolled in the CRP. However, as a benefit for doing so, they will be provided feedback as to their progress over the three month study period and be administered a brief, repeated neuropsychological evaluation. Given the minimal risk involved in such and that this is routine clinical care, we have determined this to be eligible for an expedited review and prepared the application as such. Should you require any further information, please do not hesitate to contact me. Thank you in advance for your time.

9. Cover letter – Sample 2 To the IRB: Enclosed please find one original and a copy of my IRB proposal entitled Unemployment in Multiple Sclerosis (MS): The role of personality, coping, and health-related behaviors, which is a study pending funding with the National Institutes of Health as part of a larger Mentored Patient Research Career Development Award (K23). Given that this will be a Federally-funded study and the minimal risk involved with the investigation, I have determined this to be eligible for an expedited review and prepared the application as such. Please also note that the title included on the consent form and brochure is a modified version of the study title. This was changed in hopes of reducing bias in part of potential participants. Should you require any further information, please do not hesitate to contact me. Thank you in advance for your time.

10. What You Must Include in an IRB application • Cover letter • IRB Initial application • Research Proposal Outline/Protocol • HIPAA/NOPP forms OR Waiver • Consent forms • CITI instructions – all study team members certifications should be submitted • If funded, copy of grant

11. IRB Initial Application • NEEDS signatures, including Dr. Gans (KIR personnel on the project?) and Dr. DeLuca (KF personnel on the project?) • Do not try to collect signatures from RRC and IRB Chairs (Dr Barrett and Dr Greene)—they sign after the proposal is considered and approved by the RRC/IRB • Brief description of project/abstract • List and SIGNATURES of all study staff • Type of study (funded, pilot, clinical trial) • IRB funds

12. IRB Initial Application • Type of Review – refer to the attachment they send to determine this – fill this in • Recruitment process – Attach flyers, brochures if applicable • Study procedures • CITI certifications • HIPAA

13. What You Must Include in an IRB application • Cover letter • IRB Initial application • Research Proposal Outline/Protocol • HIPAA/NOPP forms OR Waiver • Consent forms • CITI instructions – all study team members certifications should be submitted • If funded, copy of grant

14. Research Protocol • Abstract – lay summary • Study objectives • Significance of the study • Review of the literature • Methodology • Participants • Procedures • Analyses • Work Schedule • Budget • Dissemination • References

15. Abstract • This should be a brief introduction that summarizes the background and your objectives • Must include the population of interest, the topic, the objective and some overarching goal • Layman terms

16. Abstract – Sample 1 Declines in cognition, quality of life, well-being, and overall functioning are common following neurological insult and/or disease. Efforts to improve the overall functioning and quality of life of such individuals are paramount. The Cognitive Rehabilitation Program (CRP) at the Kessler Institute for Rehabilitation (KIR) is a comprehensive rehabilitation outpatient program which utilizes a client/family centered, multidisciplinary rehabilitation team approach to maximize potential for independence in persons with cognitive deficits due to neurological insult or disease. The program is designed to serve the unique needs of individuals at different levels of severity and stages of recovery. The traditional cognitive rehabilitation group program serves a mildly to moderately impaired population with realistic goals of return to work or community functioning. The fundamentals cognitive rehabilitation group program serves a more severely impaired population with more acute family education and caregiver needs. Individual therapies are provided for both group participants and clients with specialized needs. Comprehensive cognitive rehabilitation programs such as CRP are commonly recommended for individuals with such injuries and associated impairments in cognition and/or functioning. However, the outcomes and effectiveness of such programs have not been extensively investigated to date. The purpose of the proposed investigation is to examine the outcomes among individuals enrolled in the CRP at KIR. Pre- and post-treatment evaluations of cognition, well-being, psychological health, community participation, quality of life, productivity, and caregiver burden will be conducted among individuals enrolled in the CRP and a comparable control group to determine the effectiveness of individuals’ participation in this important program.

17. Study Objectives • BE CONSISTENT! These should later be used to state your hypotheses and help guide analyses and consistent with what you have in the abstract • Aim 1: Determine whether CRP is effective in improving cognitive function among the individuals who participate in a 12-week traditional program. • Aim 2: Determine whether CRP is effective in improving functional outcomes upon discharge (e.g., employment, driving). • Aim 3: Determine whether CRP is effective in improving overall quality of life, caregiver burden, psychological health, and awareness of cognitive deficits associated with one’s injury or disease.

18. Significance • State the population and problem • Speak to the prevalence or nature of what you are studying • How will the study influence the population or the problem • How will this inform treatment, patient care, well-being of participants, etc?

19. THE POPULATION: Neurological injury and/or disease are a substantial concern. For instance, among the general population, approximately 1.7 million individuals sustain a traumatic brain injury (TBI)1 and stroke occurs in an estimated 795,000 individuals each year.2 THE PROBLEM: Detriments in cognition, quality of life, well-being, and overall functioning are common following such neurological insult and/or disease. Cognitive impairments frequently result in decreased independence, as they affect ability to perform such activities of daily living as management of medication regimen and handling personal finances, shopping, and driving among others. These deficits may also result in difficulty maintaining employment, increased financial, psychological, and physical burden on caregivers, and ultimately increased cost to society. SIGNIFICANCE/WHY DO THIS STUDY? Although non-pharmacological interventions are widely used in rehabilitation of such deficits, evidence base for the effectiveness of these interventions is limited, at best. WHAT YOU CAN ACHIEVE WITH THE STUDY: The proposed investigation aims to examine the effectiveness and outcomes of an existing rehabilitation program for individuals who have sustained such injury and or illness and have documented cognitive, functional, and psychosocial impairments. While the specific aims are to examine the components and outcomes of the treatment, the overarching goal of the investigation is to better the lives of individuals seen in CRP.

20. Review of the Literature • Should NOT be bullet points or a list of who has done what you are aiming to do • A comprehensive review of the literature • The population • The specifics of what you are interested in • What has been done in the past and how this relates to what you are aiming to do • Critical review – why did others not work? What did they fail to consider? What will you do that is different?

21. Subsections • General background and significance of the problem • Effects of rehabilitation on cognition in neurological conditions • Effects of rehabilitation on functional outcomes, quality of life, integration, caregiver burden, and psychological functioning.

22. Methods • Participants • How and who do you plan to enroll • Inclusion/exclusion criteria • How classified? • Risks to participants • Special or at risk populations • Procedures • What will be undertaken (walk the reader through this) • Measures, tests, etc.

23. Analyses • State the SPECIFIC analyses you intend to do and KNOW WHY! • Here is where you can also take your study objectives and assign hypotheses and proposed analyses • Include a POWER ANALYSIS and realistic goals as to how you anticipate obtaining your sample

24. Data Analysis – Sample 1 Data will be analyzed using Predictive Analytic Software (PASW, formerly known as SPSS) version 18. Data will be subjected to correlational and linear regression analyses to establish cognitive and functional correlates and predictors of positive treatment outcomes and repeated measures ANOVA to determine the effects of cognitive intervention on various constructs examined over the course the 12 week period. More specifically, the following analyses will be conducted to address the following study aims and related hypotheses.

25. HYPOTHESES & ANALYSES • Aim 1:Determine whether CRP is effective in improving cognitive function among the individuals who participate in a 12-week traditional program. • Hypothesis 1: Individuals enrolled in the traditional CRP will demonstrate an improvement in their cognitive functioning compared to controls • Proposed analyses: Two factor repeated measures ANOVA will be employed with cognitive test variables as the primary outcome variables and time and group as independent factors.

26. HYPOTHESES & ANALYSES • Aim 2: Determine whether CRP is effective in improving functional outcomes upon discharge (e.g., employment, driving). • Hypothesis 2: Individuals enrolled in the CRP will demonstrate greater improvements in their functioning following a 12 week period than controls. • Proposed analyses: Initial Chi-square analyses will conducted to determine whether a greater proportion of individuals enrolled in CRP have returned to work or driving. Subsequent logistic regression analyses will be conducted to determine which factors at baseline and follow-up may be most accountable for improvement in functional outcomes.

27. HYPOTHESES & ANALYSES • Aim 3:Determine whether CRP is effective in improving overall quality of life, caregiver burden, psychological health, and awareness of cognitive deficits associated with one’s injury or disease. • Hypothesis 3: Individuals enrolled in CRP will exhibit an improvement in their overall quality of life, psychological health, and awareness of deficits. Additionally, caregivers of participants in the fundamentals group will demonstrate a reduction in caregiver burden. • Proposed analyses: Two factor repeated measures ANOVA will be employed with quality of life, psychological factors, awareness measures, and caregiver burden as primary outcome variables and time and group and independent factors.

28. POWER ANALYSIS It is estimated that 173-192 subjects will be eligible for the study based on census data from CRP. Taking a conservative estimate, we predict that 175 individuals will be enrolled. Based on these numbers we will certainly have a large enough sample to conduct the primary analyses (Repeated measures ANOVA). In particular, in setting α at 0.05, we can achieve power of 0.80 and obtain a medium effect size (f = 0.25) with a minimum sample size of 34. However, with regard to regression analyses, to obtain a power of .80 with α at 0.05, we would need an approximant sample of 172 to obtain a small to medium effect size (f =.10) when using six predictors in the model.

29. Power Analysis and Determination of Sample Size – Sample 2 Approximately 280 to 300 subjects will be enrolled in the study. Assuming a 95% response rate, this will result in a sample of 266 to 285. This anticipated sample size is adequate for the regression analyses in Aims 1 and 2 to identify significant factors most related to an individual with MS̓s decision to leave the workforce. In particular, the largest first-order model expected would be that of the coping measure, which consists of 12 variables. The α for the test of this model will be set at 0.05. To achieve power of 0.80 and obtain a medium to small effect size (f² = 0.1), a minimum sample size of 185 is required to detect a significant model.87 With regard to Aim 3, a general rule of thumb in structural equation modeling (SEM) is that a sample size of 200 is adequate for moderate sized models. It is also recommended that models include 10 subjects per parameter. In SEM, it is estimated that every variable will have three parameters (its path coefficient, its variance, and a disturbance item).88 Given our anticipated sample size, this would suggest that we can develop models with up to 28 parameters, which should be more than sufficient.

30. What You Must Include in an IRB application • Cover letter • IRB Initial application • Research Proposal Outline/Protocol • HIPAA/NOPP forms OR Waiver • Consent forms • CITI instructions – all study team members certifications should be submitted • If funded, copy of grant

31. HIPAA & HIPAA Waiver • Determine if you are eligible for a HIPAA waiver • Most likely, should provide the HIPAA form • Complete what is necessary and REMOVE what is not

32. What You Must Include in an IRB application • Cover letter • IRB Initial application • Research Proposal Outline/Protocol • HIPAA/NOPP forms OR Waiver • Consent forms • CITI instructions – all study team members certifications should be submitted • If funded, copy of grant

33. Consent Forms • Take out the fillers! • For the most part, the consent should remain as written and you just need to fill in the required info OR select the part that is appropriate to you • Delete the other parts • Should be at or below an 8th grade reading level • VERY BASIC

34. Going before the RCC… • Before the RCC meeting, the committee reviews your proposal • Members provide feedback that are then summarized and provided to you to address. • They take their time with this – so should you! • You and your mentor will then be scheduled to present your proposal and address the comments to the RCC

35. OUTCOMES • Once the RRC meets, there are 3 outcomes: • Study is approved as is • Study is pending approval with minor changes • Tabled due to the need of major revisions • You will be sent a letter with the decision. May need to see you again if you have not fully addressed the comments.

36. LAST TIPS TIP 1: Don’t throw this packet out TIP 2: Actually refer to this packet and read it when ready to submit your proposal TIP 3: Devote the RIGHT time to the proposal TIP 4: Work with your mentor or anyone with research experience when drafting the proposal TIP 5: Consult a statistician

37. LAST TIPS TIP 6: Make sure the study is feasible with the amount of time and participants you have TIP 7: Use the proposal as a stepping stone for any grant applications OR publications you hope to get from your study TIP 8: PLAN AHEAD! Think of when you need this done by and work backwards. Then, times that by one and a half!

38. Questions?