breakdown of review types and expectations web viewif the “navigation pane” is not open...

CPC Reviewer Checklist—Blue FormFor protocols that test the safety, efficacy, or effect of an intervention, device, technique, procedure, or test

BREAKDOWN OF REVIEW TYPES AND EXPECTATIONS

Review Type Reviewer Directive

Medical/Scientific MD, PhD, or other qualified CPC member

Review with a focus on medical and clinical merit, clinical research design, and feasibility

DCI CPC Staff—Scientific Review Officer Review with a focus on scientific merit and alignment with DCI priorities

Statistical Statistician Review with a focus on the statistical analysis plan and validity of the research design

Pharmacy Pharmacist—Investigational Chemotherapy Service

Review with a focus on clinical merit and details of study agent handling, dispensing, and management

Consent Patient Advocate Review with a focus on language and formatting of the informed consent form

INSTRUCTIONS

1. Reviewers are responsible for reviewing the checklist sections to which they’ve been assigned. Each checklist section specifies the minimum criteria for each reviewer, but reviewers may expand their scope as desired to fit specific needs.

2. Reviewers may “jump” to their section of the checklist by clicking on the relevant link in the “Navigation Pane” to the left of this document. If the “Navigation Pane” is not open in Word, you may find it by clicking on the “View” tab of at the top of the Word window. Then select “Navigation Pane”.

3. For each review criterion, reviewers should determine whether the relevant information is consistent in all protocol-related documents.

4. For protocols assigned as CPC meeting reviews, reviewers are encouraged to contact the PI to express comments and concerns prior to the CPC meeting. The purpose of this contact is to avoid certain motions (particularly Defer or Disapprove), which can lead to significant delays in approval, by resolving issues prior to the CPC meeting. If a reviewer does not wish to contact the PI directly, the reviewer can request that his/her comments be forwarded to the PI by the CPC staff, who will then (1) mediate PI-reviewer discussion via eIRB or email, or (2) present PI response to the reviewer at the CPC meeting.

5. For protocols assigned as web-based reviews, the review process is normally completed online without the need for discussion at CPC meetings. However, discussion of a web-based review at a CPC meeting may occur if (1) any reviewer requests that a web-based review be added to the CPC meeting agenda and (2) any reviewer motions to defer the protocol. Thus, all web-based reviewers should be prepared to discuss web-based reviews at CPC meetings if asked to do so.

1v12.04.13


6. While using this checklist, a “yes” is assumed if the reviewer does not provide checks for a review criterion. For most criteria, the answer should be yes.

7. While using this checklist, if a “no” is checked for any review criterion, please provide comments, suggestions, and concerns at the end of the review section.

8. During completion of the review, some reviewers indicate the scientific merit of the protocol.

High: The research protocol significantly advances a sub-field within cancer research. These protocols might represent the “top 10%” of protocols. The primary benefit of having “high” scientific merit is that the protocol becomes eligible for the “IRB FastLane”, in which the CPC coordinates with the IRB to attempt completion of IRB review within 14 days of CPC approval.

Medium: The research protocol adds important knowledge to a sub-field within cancer research. However, the expected impact of the protocol is limited by the stated objectives and/or approach.

Low: The research protocol adds knowledge that is limited in scope, impact, and/or innovation.

9. During completion of the review, all reviewers suggest a motion for the protocol, as follows:

Approve: The protocol possesses adequate scientific merit, clinical research design, data analysis plan, data and safety monitoring plan, and data management plan. No changes are necessary.

Approve with minor editorial revisions: The protocol possesses adequate scientific merit, clinical research design, data analysis plan, data and safety monitoring plan, and data management plan. However, minor revisions requested by the CPC are required prior to approval.

Approve with modifications: The protocol meets basic CPC standards and is approvable. However it requires specific changes requested by the CPC in order to possess adequate scientific merit, clinical research design, data analysis plan, data and safety monitoring plan, and data management plan.

Defer*: In its current state, the protocol is not approvable because the protocol lacks sufficient detail. The CPC requires additional information from the PI in order to make a definitive motion. Moreover, it is anticipated that the CPC’s ability to approve the protocol will depend on the content in the PI’s response.

Disapprove*: The protocol is incomplete or suffers from deficits in scientific merit and/or subject protections.

* Upon submission of PI response and revisions, these protocols must be reviewed at a convened CPC meeting.

10. During completion of the review, a protocol priority score must be approved by the CPC. The protocol priority score is proposed by the Clinical Research Program leader.

11. Once the review is complete, upload this review checklist into eIRB by doing the following:

2v12.04.13


A. Open the protocol workspace in eIRB.B. On the left side of the workspace, click “CPC – Add Review”, and a pop-up screen will appear.C. From the dropdown list, select a recommended motion.D. Add comments as needed (these comments will not be seen by study teams).E. Attach this review checklist by clicking “Add” and selecting the file from the appropriate folder.F. Click “OK” to approve attachment of the checklist.G. Click “OK” to complete the review.

TIMEFRAME FOR REVIEW COMPLETION

1. All reviews are expected to be completed in ≤ 7 days of assignment.

3v12.04.13


MEDICAL/SCIENTIFIC CHECKLISTMaterials to Review in Detail: Protocol and eIRB submission (and Investigator Brochure, as needed)Materials to Review for Consistency: Research Summary and Consent Form

Protocol informationeIRB #: Full Protocol Title: PI: Reviewer Name: Review Date:

Protocol DescriptionSummarize the study objectives, design, inclusion/exclusion criteria, and statistical analysis plan

Primary Objective and Secondary/Exploratory Objectives

Research Design and Key Inclusion/Exclusion Criteria

Key Endpoints and Statistical Analysis Plan

Review Criteria:The protocol must clearly define and detail the following information

1. Purpose No N/AA. The protocol addresses a clinically unmet needB. The protocol advances the research fieldC. The research is ethicalD. The protocol states how/whether study conclusions will drive future research questions

2. Objectives No N/AA. Objectives are clearly statedB. Objectives are realistic and achievable

3. Design No N/AA. The trial design is consistent with current research standardsB. The trial is designed to answer the objectivesC. Sample size is consistent with current research standardsD. The research design minimizes risks and maximizes subject safetyE. The research design maximizes the potential for direct benefitF. The interventions are reasonable for the research subject populationG. The mode of study agent administration is reasonable for the research subjectsH. Adequate provisions are made to ensure blinding of the studyI. The definition of an “evaluable subject” is acceptableJ. The dose modification scheme in the event of an AE is acceptable

4v12.04.13


K. The reporting criteria for AEs is acceptableL. The current standard of care is clearly statedM. The pros/cons of study intervention compared to SOC are discussedN. Adequate provisions are made to ensure randomization of the study

4. Study Methods and Procedures No N/AA. Procedures are appropriate and related to the research objectivesB. Procedures are reasonable for the subject populationC. The treatment is based on good medical practice D. The research/treatment options fall within the standard medical practice at DukeE. The treatment is based on good medical practiceF. The duration of subject follow-up is reasonableG. The dosage of study agent is appropriate and justifiedH. Discontinuation or delay of current medications is medically or scientifically justifiedI. The protocol involves non-standard/certified or exploratory laboratory tests or experiments

- If yes, the key personnel (or entities) conducting such analyses are specified- If yes, the specified key personnel (or entities) are qualified to conduct such analyses

J. A randomization procedure is described and acceptableK. An unblinding procedure is described and acceptable

5. Statistical Analysis Plan No N/AA. Endpoints are clearly definedB. Endpoints adequately address the research objectivesC. Analyses are designed to address the research objectivesD. The analysis plan provides sufficient detailE. Planned analyses are consistent with current research standardsF. Interim analyses are appropriate for the study

6. Subject Population No N/AA. The subject population is appropriate for the proposed researchB. The subject population exists at this siteC. The expected survival time of the subject population is amenable to study participationD. The inclusion/exclusion criteria are reasonable and justifiedE. The withdrawal criteria are reasonable and justifiedF. The schedule of events can be tolerated reasonably by the subject population

7. Feasibility No N/AA. The schedule of events can be managed and completed by study team safely and effectivelyB. The protocol does not compete/interfere with other trials within the Research ProgramC. The projected study duration and annual accrual rates are appropriate

- To find accrual rates, refer to the CPC New Protocol Submission Form in eIRB Section 15.2D. The projected screen failure rate is acceptable and justified

8. Additional considerations No N/AA. Standard CPC review process is sufficient for thorough evaluation of this protocol

- If no, please suggest expertise (area and/or individual) that may be beneficialB. The investigational treatment is covered by an IND/IDE

- If no, is an IND/IDE needed?

5v12.04.13


MEDICAL/SCIENTIFIC COMMENTSComments and Suggestions to PI (these do not require response from PI):

Concerns, Clarifications, and Modifications (these require response from PI):

Scientific Merit:HighMediumLow

Motion (see Instructions on page 2 for specific definitions):ApproveApprove with minor editorial revisionsApprove with modificationsDeferDisapprove

I need to see PI response before protocol is sent to Chair for final approval:YesNo

Time Spent Reviewing this Protocol (in 0.25 hour increments):

6v12.04.13


DCI CHECKLISTMaterials to Review in Detail: Protocol and eIRB submission (and Key Cited Literature, as needed)Materials to Review for Consistency: Research Summary and Consent


Protocol DescriptionSummarize the background, rationale, and prior experience with the study intervention


1. Background and Rationale: No N/AA. Existing literature from pre-clinical and/or clinical studies support the protocol objectivesB. Unpublished data from pre-clinical and/or clinical studies support the protocol objectives

2. Scientific Merit: No N/AA. The protocol has clearly defined scientific objectivesB. The protocol clearly articulates the following information: No N/A

- Purpose, Objectives- Design, Methods and Procedures, Planned analysis

- The randomization scheme is specified- Correlative science is justified and described in sufficient detail- If randomized Phase II or III, stopping rules or independent DSMB is specified- If interim analysis is included, the responsible person/committee is specified- Drug dosage/regimen is consistent with standard of care or prior testing

- Clinical, Regulatory, and Ethical Responsibilities- Responsibility for site monitoring and auditing is clearly described

C. The protocol tests a novel conceptD. The protocol tests a first-in-man interventionE. The protocol includes control groups that permit the derivation of meaningful conclusionsF. Regardless of outcome, the protocol collects data that can direct future researchG. The protocol validates a less-developed concept in a more physiologically meaningful contextH. The protocol involves non-standard/certified or exploratory laboratory tests or experiments

- If DCI PI-initiated, key personnel (or entities) conducting such analyses are specified- If DCI PI-initiated, key personnel (or entities) are qualified to conduct such analyses

3. Subject Population: No N/AA. The subject inclusion criteria have a sound scientific basisB. The subject exclusion criteria have a sound scientific basisC. Stratification of the subject populations is justified scientifically

7v12.04.13


4. FeasibilityA. The Protocol Priority Score is provided and justifiedB. The PI and/or Duke Clinics have serve the relevant patient population(s)C. The accrual rate and accrual timeframe are reasonable and appropriate

- Accrual rate and timeframe information are accurately stated in eIRB documentsD. The requisite collaborators/expertise are included as key personnelE. The DCI provides an adequate infrastructure/research environment to support the study

5. DCI Considerations: No N/AA. Funding sources and their specific contributions are clearly statedB. The protocol collects data or specimens that can stimulate translational researchC. The protocol involves collaboration between the study PI and another Duke investigatorD. The data and safety monitoring plan complies with Duke DSMP requirements

- If DCI PI-initiated, the DCI DSMP-specified monitoring plan is included- If DCI PI-initiated and multi-site, an external site monitoring plan is included

E. The data management plan complies with Duke DSMP and RDSP requirementsF. The adverse event reporting plan meets DCI Safety Desk and/or DSMP requirementsG. A pathology review form is submitted for collection of tissues for research-related purposesH. If Oncology CRU is Owning Organization, the study coordinators are Oncology CRU staffI. Sign-offs from Disease Group Leaders and Statisticians are appropriate and completeJ. The trial characteristics have been registered in the Internal Working DatabaseK. In consent form, the DCI and CTQA have ability to review subject medical recordsL. If study involves Radiation Therapy, the Rad Onc group has provided inputM. The study has a cover sheet that meets CTRP requirements

6. Additional considerations: No N/AA. Standard CPC review process is sufficient for thorough evaluation of this protocol

- If no, please suggest expertise (area and/or individual) that may be beneficialB. The investigational treatment is covered by an IND/IDE

- If yes, an FDA safe-to-proceed letter or equivalent is uploaded into Section 08 of eIRB- If yes, research data will not be stored in inferior database (i.e. Excel, Redcap, etc.)- If no, is an IND/IDE needed?

DCI COMMENTSComments and Suggestions to PI (these do not require response from PI):



Motion (see Instructions on page 2 for specific definitions):Approve

8v12.04.13


Approve with minor editorial revisionsApprove with modificationsDeferDisapprove

Protocol Priority Score:PI proposed: CPC proposed:



9v12.04.13


STATISTICAL CHECKLISTMaterials to Review in Detail: ProtocolMaterials to Review for Consistency: Research Summary and eIRB submission



1. Objectives and Endpoints No N/AA. The primary and secondary objectives are clearly definedB. Endpoints are consistent with study objectives

2. Research Design No N/AA. The planned sample size is clearly statedB. The planned sample size is justifiedC. Sample size justification for hypothesis testing includes: No N/A

- Type I error for sample size calculations- Alternative hypothesis parameter values and corresponding power- If survival analysis is primary objective, targeted number of events is given- If parameter estimation is involved, sample size is justified (i.e. confidence intervals)- Clinical assumptions made in sample size calculations are justified by literature- Estimated time to target accrual and accrual rate are provided- Guidelines are provided to differentiate a positive vs. negative study

3. Interim Analysis and Study Monitoring No N/AA. Interim efficacy or safety analyses are clearly describedB. Plans for stopping accrual during monitoring are providedC. A detailed monitoring plan is providedD. For Phase I studies No N/A

- The dose-escalation scheme is described clearly- The MTD is clearly defined- DLT is clearly defined

4. Statistical Analysis Plan No N/AA. Methods of statistical analysis are described clearlyB. Methods of statistical analysis are appropriateC. The definition of an “evaluable” subject is clearly definedD. Statistical handling of ineligible or non-evaluable subjects is described and appropriate

5. Statistician InvolvementA. Reviewer should confirm that the study statistician: No N/A

10v12.04.13


- Is indicated in the protocol- Is listed as key personnel in eIRB- Is aware of his/her involvement in the study- Confirm that the protocol contains the most recent statistical analysis plan

6. Additional Considerations No N/AA. Standard CPC review process is sufficient for thorough evaluation of this protocol

- If no, please suggest expertise (area and/or individual) that may be beneficial

STATISTICAL COMMENTSComments and Suggestions to PI (these do not require response from PI):






11v12.04.13


PHARMACY CHECKLISTMaterials to Review in Detail: Protocol (and Investigator Brochure and Package Insert, as needed)Materials to Review for Consistency: Research Summary, Consent, and eIRB submission



1. Study Schema No N/AA. A schema is providedB. The schema describes the research plan clearlyC. The schema reflects the correct dosing, days, and agentD. The study agents are listed in the order they are to be administered

2. Subject Population and Inclusion/Exclusion Criteria: No N/AA. Maximum and minimum lab values for tests on organ function are appropriateB. The route of drug administration is appropriate for the subject populationC. Vulnerable populations are excluded, as appropriate for study agentC. Concomitant medications that are excluded from are justified

3. Drug Formulation, Availability, and Preparation: No N/AA. The pharmaceutical data sheet is provided in the eIRB submission B. The Investigator’s Brochure is provided in the eIRB submissionC. Basic study agent information is included in the protocol

- NSC#, chemical name, other names, dosage forms, ingredients, packaging, supplierD. Instructions for study agent preparation are clear and understandableE. Study agent stability and storage requirements are clearly stated

- For original dosage form, reconstituted solution, and final diluted productF. The person or service which is responsible for storage and preparation is appropriateG. The route of administration is clearly statedH. Instructions for study agent preparation are clear and understandableI. The protocol has accounted for anticipated or known drug-drug interactionsJ. The protocol and consent form have disclosed significant risks and adverse events

4. Treatment Plan:A. Required Information No N/A

- The generic drug name, dose, route, and duration/rate of infusion is provided- The order of drug administration is clearly delineated- The stability data support the schedule and method of administration- The required supplemental medications are described in the treatment plan- Investigation agents are described as such (i.e. from non-commercial source)

12v12.04.13


- The treatment cycle duration is specified- The process for study drug ordering is clearly described- An adequate plan for study drug accountability is provided

B. Consistency No N/A- Treatment plan is consistent with study objectives and background- Instructions are explicit- Doses are expressed in same and correct units- Doses are delineated per dose and not per day- For NCI IND agents, treatment section is consistent with NCI monograph- All references to appendices refer to the indicated appendix

C. Dose Rounding Guidelines No N/A- Guidelines are needed and provided- Guidelines are appropriate, brief, and simple to use- Doses are rounded to the nearest tablet or half-tablet size

D. Parenteral Administration No N/A- Drugs are prepared in accordance with practitioners local and institutional policies- Drug dosage is stated as total amount of drug administered from a single container

E. Oral Administration No N/A- Drug dosage/schedule is described as drug amount for each time of administration- Instructions for concomitant food or dietary restrictions are included

5. Ancillary Treatments No N/AA. Cytokine treatment is appropriate for the treatment regimenB. Other treatments (radiotherapy, surgery, anti-emetics, etc.) are described clearlyC. Combination therapy is justified and feasible

6. Dose Modification and Management of Toxicity No N/AA. The dose modification scheme is appropriateB. The factors that influence dose modification are clearly statedC. Dose modifications are expressed as dose change, and not % of starting doseD. The effect of adverse events on dose modification is described

7. Additional considerations No N/AA. Standard CPC review process is sufficient for thorough evaluation of this protocol

- If no, please suggest expertise (area and/or individual) that may be beneficial

PHARMACY COMMENTSComments and Suggestions to PI (these do not require response from PI):



13v12.04.13





14v12.04.13


CONSENT CHECKLISTMaterials to Review in Detail: Consent FormMaterials to Review for Consistency: eIRB submission, Research Summary, and Protocol


Review Criteria:The protocol must clearly define and detail the following information.

No N/A1. The length of the consent form is reasonable considering the subject population2. The consent contains all of the following DUHS IRB-required sections: No N/A

A. Who will be my doctor on this studyB. Why is this study being doneC. How many people will take part in this studyD. What is involved in the studyE. How long will I be in this studyF. What are the risks of the studyG. Are there benefits to taking part in the studyH. What alternatives are there to participation in this studyI. Will my information be kept confidentialJ. What are the costsK. What about compensationL. What about research-related injuriesM. What about my rights to decline participation or withdraw from the studyN. Whom do I call if I have questions or problemsO. Statement of consent

3. The consent form is written using lay languageA. Tests and procedures are described adequately

4. The consent clearly and accurately describes the purpose of the research5. The consent clearly and accurately describes the subject’s involvement6. All acronyms in the consent are spelled out prior to first mention of the acronym7. The risks are categorized (i.e. more common, less common, with or without percentages, etc.)8. Within each risk category, the specific risks are alphabetized (easier for subjects to find risks)9. For optional sub-studies: No N/A

A. The opt-in/opt-out language is understandableB. The placement of sub-study explanations in the consent is logicalC. The sub-studies provide space for the subject to provide initials

10. The numbers of subjects is consistent in the consent, eIRB, research summary, and protocolA. In eIRB submission, subject number should be provided in Section 10.

15v12.04.13


CONSENT COMMENTSComments and Suggestions to PI (these do not require response from PI):






16v12.04.13

breakdown of review types and expectations web viewif the “navigation pane” is not open...

Documents