RFA-CA-18-029 Frequently Asked Questions

Cancer Prevention Clinical Trials Network (CP-CTNet): Data Management, Auditing, and Coordinating Center (DMACC) (U24)

Last updated: October 26, 2018

Note: Questions have been modified for clarity and thus the answers in this FAQ document should be considered final.

1. (Received by 10/1/2018) DCP has previously verbalized various focus areas for the early phase clinical trials program. Is there still interest from the DCP in these areas?

Answer: The focus areas that have been verbalized by DCP in the Board of Scientific Advisors presentation (e.g., immunoprevention, optimizing risk-benefit, topical/regional approaches) are still of interest, but should not be seen as limiting to the application you might propose.

2. (Received by 10/1/2018) Can we discuss potential candidate agents with DCP staff prior to application submission?

Answer: No.

3. (Received by 10/1/2018) If we have additional detail that we think would be useful in our application, can we add appendices?

Answer: Please see NIH Guide Notice, NOT-OD-17-098 for updated appendix policies - https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-098.html. The policy states that only limited information is allowed to be submitted in the appendices. Per the Notice, "Beginning with applications submitted to the NIH, AHRQ, or NIOSH for due dates on or after January 25, 2018, the only allowable Appendix materials are:

• Blank data collection forms, blank survey forms and blank questionnaire forms – or screenshots thereof. 
• Simple lists of interview questions.
• Blank informed consent/assent forms
• Other items only if they are specified in the FOA as allowable Appendix materials."

If an application is submitted with appendix materials that are not in compliance with this policy, it will be withdrawn as non-compliant.

4. (Received by 10/1/2018) Can you provide any additional information regarding the Multiple Delayed Onset section of the application? 

Answer: Additional information on how to fill out the application forms can be found at: https://grants.nih.gov/grants/how-to-apply-application-guide/forms-e/general/g.500-phs-human-subjects-and-clinical-trials-information.htm#Delayed. Additional information on the Clinical Trials Requirements for Grants can be found at: https://grants.nih.gov/policy/clinical-trials.htm.

5. (Received by 10/1/2018) Are the attachments for the Research Strategy section included in the 30-page limit? 

Answer: The 30-page limit refers to the Research Strategy only. Attachments are separate.

6. (Received by 10/1/2018) Can AOs compete with multiple LAOs?

Answer: Any AO can be part of multiple UG1 applications (the AO can associate with multiple LAOs). The strengths that the AO would bring to each UG1 application should be outlined in that application.

7. (Received by 10/1/2018) Is the Rapid Response Restricted Fund ($100,000) included in the maximum budget of $1,250,000 in direct costs or in addition to it? Does it require justification?

Answer: Yes, the Rapid Response Restricted Fund ($100,000) is part of the total budget (in years 2-5 only). It does not require justification.

8. (Received by 10/1/2018) Are supplemental funds request (for biomarkers, for example) possible? Or are these costs (endpoint analysis) supposed to be estimated as part of the $1,250,000 in direct costs?

Answer: Primary endpoints and limited secondary endpoint analyses are part of the direct costs ($1,250,000 per year) such that the clinical trial results will be interpretable. There may be opportunities in the future for additional (secondary, etc.) biomarker studies, but the estimated costs in the current applications must cover the costs necessary to interpret the results of the clinical trials.

9. (Received by 10/1/2018) Under Personnel Costs, what is meant by Lead Site Coordinators? Is this at each AO, per trial, or for the LAO only?

Answer: This refers to the LAO only.

10. (Received by 10/1/2018) What kind of network-wide administrative support will the DMACC provide?  Please give us examples. Differentiate from "all aspects of study operation," which are handled by the LAO.

Answer: The DMACC will schedule and facilitate network-wide meetings for both the leadership and all staff; it will ensure use of standardized Common Data Elements (CDEs) for similar elements across trials; it will create network-wide SOPs. CP-CTNet Sites will still be responsible for study specific calls.

11. (Received by 10/1/2018) What is meant by the recruitment efforts done by DMACC? Is this on a trial specific basis or will these be overall prevention recruitment materials? In other words, will the DMACC be developing, for example, trial-specific recruitment brochures?

Answer: The DMACC will be responsible for overall, cross-network recruitment efforts. Trial specific materials will be the responsibility of the CP-CTNet Sites.

12. (Received by 10/1/2018) Goal & Scope: conduct trials w/ single or combinations, or other modalities. What do you mean by "other modalities"?

Answer: Surgery or other ablative procedures (e.g., photodynamic therapy), for instance.

13. (Received by 10/1/2018) What is meant by prevention of recurrence – secondary cancer prevention; or do you mean prevention of second primary cancers in survivor populations?

Answer: Prevention of recurrence can refer to recurrence of a premalignant lesion or a second primary cancer.

14. (Received by 10/1/2018) For the 10 therapeutic clinical trials requested in Attachment 3, what sort of trials are you looking for? Are you looking for us to demonstrate our capacity to run phase I/II trials in general? Are you looking for further examples of investigator-initiated trials? Or could we use cooperative group/industry-sponsored trials?

Answer: The therapeutic trials refer to phase 0-II trials that demonstrate the Site’s capability to perform early phase clinical trials. You can use any type of trial you wish that best demonstrates your capabilities.

15. (Received by 10/1/2018) Are biosketches required/recommended for all AO PIs?

Answer: Yes, required.

16. (Received by 10/1/2018) What is the Scientific Leadership – will this be the LAO team plus the AO PIs? Or does this include the Steering Committee?

Answer: Scientific Leadership refers to the CP-CTNet Site (=LAO and AOs), not the Steering Committee.

17. (Received by 10/1/2018) For the Research Strategy, where do we add references – at the end of each subsection, at the end of the research strategy document, or in the R&R Other Project Information Form? If references are to be included at the end of each subsection, or at the end of the research strategy, do they count toward the 30-page limit?

Answer: References will not count toward to the 30-page limit. References are included in an attachment. This Bibliography & References Cited attachment should include any references from the Research Plan and the Human Subjects and Clinical Trials Information Form.

18. (Received by 10/1/2018) For Attachment 2, should references be included at the end of each sample concept? If so, do they count toward the 10-page limit?

Answer: Include references in the Bibliography & References Cited attachment (as in Question #18), they will not count toward the 10-page limit.

19. (Received by 10/1/2018) Do we discuss both prevention and therapeutic trials in Attachment 1?

Answer: The goal of Attachment 1 is to provide details about the Site’s early phase clinical trial capabilities, with the focus being on prevention trials. For applicants who have only performed therapeutic trials, Attachment 1 provides an opportunity to illustrate their therapeutic trial capabilities. Sites that have performed both prevention and therapeutic trials should describe both types of studies. As a reminder, the focus of this RFA is on prevention trials and capabilities to perform early phase prevention trials.

20. (Received by 10/1/2018) For Attachment 3, you requested that we list "List Phase 0, I and II prevention clinical trials." Do you want only cancer prevention clinical trials, or all disease prevention clinical trials? The FDA’s definition of Phase 0, I, and II trials include only agent interventions. However, clinicaltrials.gov lists phases for some behavioral interventions. For Attachment 3, do you want us to include clinical trials for cancer prevention behavioral interventions?

Answer: Only cancer prevention trials should be included in Attachment 3. This can include behavioral intervention studies for cancer prevention.

21. (Received by 10/1/2018) For Attachment 3, do you want phase 0, I, and II prevention trials that use an investigational agent for smoking cessation?

Answer: No.

22. (Received by 10/1/2018) For Attachment 3, if the AO or LAO was the lead Site of a multi-site study, do you want the overall trial open date/close date/planned accrual/achieved accrual, or the Site’s trial open date/close date/planned accrual/achieved accrual?

Answer: Attachment 3 is based on the overall trial.

23. (Received by 10/1/2018) For Attachments 4 and 5, should we list number of participants screened and accrued, and accrual rates projected and achieved:

1. For each of our AOs separately? or
2. For just those three AOs included in Attachment 3? or
3. For the trial as a whole (even if it included accrual Sites that aren’t an AO)?

Answer: For Attachment 3, list completed and ongoing trials from the LAO and up to three AOs. This would include trials led by the AO even if the LAO did not oversee the trial. 

For Attachment 4, data should be included for the LAO and each proposed AO broken down by Site within each trial that was listed in Attachment 3. AOs that participated in the trials included in Attachment 3 should be listed with Site specific information in Attachment 4. If a Site contributed to a study but is not a proposed AO for this grant, their accrual should not in listed in Attachment 4. The accrual from these Sites would be captured as part of the overall trial accrual in Attachment 3.

Attachment 5 shows the trial timelines for the studies listed in Attachment 3.

24. (Received by 10/1/2018) Do we need to submit a budget with each Sample Cancer Prevention Clinical Trial Concept?

Answer:  No.

25. (Received by 10/1/2018) If we do not have to submit a budget with each Concept, do the costs of the first two studies need to be included with the Overall Budget?

Answer: The costs of the concepts can be used to inform the Overall Budget; they do not need to be specifically included.

26. (Received by 10/1/2018) Is the R&R Subaward Budget Attachment Form required with the application if there are no subawards in the initial budget period?

1. The instructions read "Note on Subawards/Consortiums: If you have a subaward/consortium, you must use the R&R Subaward Budget Attachment(s) Form in conjunction with the R&R Budget Form".-We do not plan to establish subawards in the initial budget period, although we will have a consortium and we have identified the organizations that will participate with us as AOs. The AOs will participate in trials once the studies have been identified.Do we need to submit Subaward budget attachments with the initial application?
    
2. If we propose AOs in the Sample Trial Concepts, do we need to submit R&R Subaward Budget Attachment(s) Form for each AO that participate in the Sample trials?

Answers:

• The "Costs of Clinical Trials Performance" in the parent applicant budget should be sufficient to cover any/all of the costs of the subaward to an AO for their participation in an approval trial. These costs will be restricted in any subsequent Notice of Award, pending approval from NCI on specific trials. When the recipient is requesting approval for a study, this request should include a budget for the parent award along with any subawards to the participating AOs. Once a trial approval is communicated to the recipient, they then have the authority to rebudget into a subaward for the execution of that approved study.
   
• No, a budget for the Sample Concepts should not be submitted in the initial application. If the applicant anticipates requesting approval to do one of the sample concepts, should their application be funded, any allowable costs associated with that trial should be included in the "Costs of Clinical Trials Performance" in the parent applicant budget.

27. (Received 10/2/2018) Will the CP-CTNet Sites do data entry for their trials or will that be the responsibility of the DMACC?

Answer: The preferred method would be for CP-CTNet enrolling Sites to be responsible for data entry.

28. (Received 10/2/2018) From the budget cap, it seems you are anticipating smaller, cheaper trials than in the present consortia. If cross-consortia trials emerge, will there be an opportunity to expand budgets?

Answer: This is not necessarily the case. Funding for specific studies will come from multiple budget years for each Site to reflect the accrual and work performed over multiple years. The cross-network studies will pull from the budgets from all the participating CP-CTNet Sites and therefore could support more expensive trials. Biomarkers will need to be prioritized, focusing on primary and important secondary endpoints required to interpret the study results. Additional outside funds, such as those from institutional, foundation, or other grant programs, may be required to explore additional secondary endpoints.

29. (Received 10/2/2018) With the establishment of DMACC, what kind of data management capacity is needed for the LAO?

Answer: The LAO will need to provide plans to assure quality of, and monitor adherence to, the trial protocol and data collection. The LAO will also need to have a process for verifying participant eligibility and randomization.

30. (Received 10/2/2018) The typical study in the present cycle had a project period of about 2 years. Will trials that are projected to run for longer periods be acceptable?

Answer: Yes. Most prior studies have taken 2 to 4 years to complete and studies that are expected to take multiple years are appropriate for this FOA, within reason. NCI anticipates trying to renew this FOA in a timely fashion such that studies begun in the later years of this program can be completed in the future iteration of CP-CTNet.

31. (Received 10/2/2018) But the data is not viewable for QA/QC if it is going to the DMACC?

Answer: The LAO will have access for all the trial data which they oversee.

32. (Received 10/2/2018) Will the LAOs be performing monitoring visits?  

Answer: No.

33. (Received 10/2/2018) Will the LAO have access to the submitted data in real time?

Answer: Yes.

34. (Received 10/2/2018) Will the LAO be querying the data in the database?

Answer: The DMACC and LAO will need to develop a collaborative approach for data queries and resolution.

35.(Received October 8, 2018) While the instructions for this FOA are clear in what should be described about proposed Affiliate Organizations (AOs), it is unclear as to budget requirements for their participation in to-be-determined clinical trials. Can you please clarify that the Lead Academic Organization (LAO) should not include separate subcontractor AO budgets, and that anticipated funding for AOs should be accounted for in the LAO line item budget for the cost of the clinical trials?

Answer: Please see the response to question 26. Since you don’t actually know for sure which of your AOs will be involved in approved studies, you don’t need to include, although you can include subaward budgets for year 1. However, since you do anticipate that there will be subawards for studies eventually, costs that include AO participation should be included in the LAO line. The award will be re-budgeted once you have been approved for specific studies.

36. (Received October 8, 2018) From the number of patients planned on studies (170 for the entire 5 years), it seems that you are anticipating fewer and smaller trials than in the present consortium?

Answer: Not necessarily. Those numbers are the minimum requirement. The complexity of studies and the number/cost of secondary will determine the actual number of participants who will be accrued. There was a wide range in accruals per consortium in the prior program.

37. (Received October 9, 2018) Based on answers to the questions 26 and 31, is it correct to assume the budget requires justification for only the LAO labor and travel with the remaining balance (the difference between $625,000 and $1,250,000) designated as restricted "Costs of Clinical Trials Performance" with no other breakdown needed?

Answer: There should be a general justification–i.e., estimated number of AOs, what sorts of costs are expected (personnel, travel, incentives, etc.) — and it can all be lumped under "Costs of Clinical Trials Performance."

38. (Received October 9, 2018) For this grant, do the subrecipient indirect costs count against the proposed funding of $625,000 in the initial year and $1,250,000 in the subsequent years?

Answer: Because the line item is just "Costs of Clinical Trials Performance," any F&A costs (indirect costs) that go to subawards/AOs as a part of that line item would count against the cost cap. Only when actual subawards are included in the application budget would the F&A on the subawards not count towards the cost cap.

39. (Received October 12, 2018) Will the individual trials be funded separately, or do we need to factor those costs into the amounts allocated for year 1, and years 2-5?

Answer: Individual trials will not be funded separately. The study conduct, patient care, as well as primary and major secondary endpoints, should all be done within the $625,000 in year 1 and $1,250,000 in years 2-5.

40. (Received October 14, 2018) Can an investigator who is named on the U24 leadership team also be named as a site PI on a UG1 application?

Answer: No. The RFA states, "The PDs/PIs of applications submitted in response to this FOA must not be named as Senior/Key Personnel or Other Significant Contributors on any teams submitting applications to the companion FOA, RFA-CA-18-030." The intent of this statement is that any key personnel on a U24 cannot be key personnel on a UG1 and vice versa; this includes serving as an AO site PI.

41. Attachment 3 requires "years open" as does Attachment 4. Does that mean the duration of time, say 1.25 years? Can we use months open instead? Or are you referring to the calendar year, say Sept 2013 through August 2016?

Answer: Attachment 3 and Attachment 4 both ask for information on “years open”. This refers to calendar time, ex. Sept 2013-Aug 2016.

42. Besides the named personnel in the budget for the LAO administration, can we include biosketches for personnel that we anticipate will be involved in running trials? The number of biosketches multiplies fairly quickly for these key personnel. Finally, for the protocol concepts, should we add the PI biosketches or a letter from the protocol PIs?

Answer: Biosketches should be included for anyone who would be considered key personnel. Key personnel are program director/principal investigator (PD/PI) and other individuals who contribute to the scientific development or execution of a project in a substantive, measurable way, whether or not they request salaries or compensation.

Biosketches for the PIs and any key personnel of the protocol concepts should also be included.

43. Can protocols in attachment 2 have biomarker lab sites outside of the named AOs?

Answer: If it is fee-for-service lab it can be outside of your AOs, otherwise the institution of the biomarker lab site would need to be named as a non-accruing AO since you will have key personnel from the lab.

44. Because we want to understand the roles and differences between clinical research auditing and monitoring, two distinctly different functions, please clarify what distinguishes the two functions within the context of both the RFA-CA-18-030 and the companion RFA-CA-18-029.

Answer: Monitoring will be the responsibility of the UG1 Site. Monitoring is the act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, standard operating procedures (SOPs), GCP, and applicable regulatory requirements. It is a continuous process, can be conducted on-site or off-site, and involves oversight of all patients on a trial. Study monitoring includes:

• Precise tracking of patient accrual
• Ongoing assessment of patient eligibility and evaluability
• Adequate measures to ensure timely submission of study data
• Adequate measures to ensure timely medical review and assessment of individual patient data
• Timely reporting of adverse events and treatment-related morbidity information
• Periodic evaluation of outcome measures and patient safety information

Auditing will be the responsibility of the DMACC. Auditing is a systematic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the date recorded, analyzed, and accurately reported according to the protocol, sponsor’s standard operating procedures, GCP, and the applicable regulatory requirements. It is a snapshot in time (as opposed to the continuous nature of monitoring), commonly an on-site process, and consists of reviewing a subset of patients on a trial.

The specific purposes of the auditing program are to document the accuracy of data submitted to Medidata Rave and NCI/DCP, to verify investigator compliance with protocol and regulatory requirements, adherence to the policies and procedures of the CP-CTNet and, if necessary provide site staff with resources for a more thorough understanding of the regulatory requirements, good clinical practices (GCP), data collection and data management practices. The major objective of the audit program is to verify study data that could affect the interpretation of primary study endpoints. The three components of a study audit are:

• IRB/Informed consent content review
• Pharmacy and drug accountability; and
• Patient case review