We appreciate your interest in the NIH Common Fund Acute to Chronic Pain Signatures (A2CPS) funding opportunities and hope that you and your team will submit an application.

The NIH hosted a pre-application interactive Q&A webinar (NOT-RM-18-021) for the five program FOAs on September 6, 2018. The slides from the webinar are now available for download. In addition, this Frequently Asked Questions page is now updated to reflect questions received during the webinar.


What is the NIH Common Fund?

The NIH Common Fund, managed by the Office of Strategic Coordination in the Office of the Director, supports cross-cutting trans-NIH programs that require participation by multiple Institutes and Centers. Common Fund programs are intended to be transformative, catalytic, synergistic, cross-cutting, and unique. This program is funded as a short-term, goal-driven strategic investment, with deliverables intended to catalyze research across multiple biomedical research disciplines. More information can be found at https://commonfund.nih.gov/

Who should I contact if I need assistance with something that isn’t listed here?

For questions related to the Multisite Clinical Center RFAs (RFA-RM-18-033, RFA-RM-18-034) or the Clinical Coordination Center RFA (RFA-RM-18-035), please contact:

Linda L. Porter, Ph.D.

National Institute on Neurological Disorders and Stroke (NINDS)

Telephone: 301-435-7572

For questions related to the Data Integration and Resource Center (RFA-RM-18-031) or Omics Data Generation Centers (RFA-RM-18-032) RFAs, please contact:

John Satterlee, Ph.D. 
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1020

Will the applicant webinar be posted online afterward?

No. However this list of common FAQs will be updated to reflect the questions asked during the webinar, and the webinar slides are now available here

Are multi-PI applications allowed?


What would be the eligibility rules regarding foreign researchers and institutions?

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components,
asdefined in the NIH Grants Policy Statement, are allowed.

Can NIH intramural investigators apply to any of the funding announcements?

Yes, although the requests by NIH intramural scientists will be limited to the incremental costs required for participation. These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. 

What are “U” grants and how are they different from R01s?

The FOAs use the cooperative agreement funding mechanism which is a “U” mechanism. A cooperative agreement supports discrete, specified, circumscribed projects to be performed by investigators in an area representing their specific interest and competencies and is used when substantial and continuous NIH programmatic involvement is anticipated.

Can I be a PI on an application for one FOA and also be a PI or multi-PI on an application submitted to another FOA?

Yes, however, your participation as a PI is limited by your available percent effort.

What are the plans for data and resource sharing for this program?

NIH plans to deposit information generated by this program (for example, patient data and technical protocols) in the Data Integration and Resource Center (DIRC). Data, protocols, analysis tools, software, and other resources generated by the program will be available to the research community through the A2CPS portal.  Data will also be stored in the appropriate public or controlled-access repositories.  See A2CPS RFAs for more details about data sharing requirements. 

Will the applications submitted to all the FOAs be reviewed in one study section?

Applications will be reviewed in an appropriate special emphasis panel.

Can NIH provide additional guidance on including milestones in the application?

All Common Fund projects are goal driven and require milestones. Milestones are intermediate steps towards the completion of concrete goals and must include clear and quantitative criteria for success. Yearly quantitative milestones are required to provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. The application must include clearly-specified, well-defined milestones, quantitative go/no go decision points, and timelines for assessing progress.

Applicants must provide a timeline and detailed quantitative annual milestones spanning the funding period. If selected for funding, applicants will work with NIH staff to develop more granular quarterly milestones for each year of funding. 

What are some examples of quantitative milestones?

Examples of quantitative milestones include, but are not limited to, enrollment numbers, completion of enrolled patient follow up, and data deposition into the DIRC. Note that prior to an award, NIH staff and the applicants will finalize an agreed upon set of milestones that will be included in the notice of grant award.

What must my application contain to be considered responsive?

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review (CSR) and responsiveness by program staff of the trans-NIH working group.  Applicants must describe their research plans, which must include a timeline and detailed qualitative milestones, as well as a data sharing plan.  Applicants to all RFAs must specifically propose at least ten biomarkers, and must justify (using the literature or their own preliminary data) why these biomarkers may be useful for capturing the transition from acute to chronic pain.  Applicants should include their qualifications (including past successes) and should describe how the project will be managed.  Please be sure to read the RFA thoroughly to ensure that all points have been addressed.

In addition to the points outlined above, applicants should be sure to address all the key points that are specific to the particular RFA in order to be responsive.

How did the NIH estimate the projected cohort size and number of biomarkers?

This study is informed by an NIH-conducted power analysis that indicated that in order to identify one to ten potential high value biomarkers (with 15% predictive effect), 40 biomarkers should be tested in each cohort. The assumption made from the literature was that these pain conditions would have an expected transition rate to chronic pain of approximately 46%, and therefore the calculation was that each cohort must include approximately 1800 patients.  These numbers (approximately 40 biomarkers and 1800 patients per pain cohort) may be adjusted after similar power analyses are carried out by applicants, and additional information is obtained on transition rates of each specific pain cohort. 

May applicants consider other assumptions than the assumptions used by NIH in the initial power analysis?

Yes.  However, the budget for each RFA is fixed, and applicants should take this into account in their research plans.

How will biomarkers be selected?

The candidate biomarkers to be tested as primary outcomes in the two studies will be selected by a panel of external experts, consortium awardees, and NIH staff, who will consider the most promising biomarkers of transition or resilience to chronic pain based on current evidence from the literature and/or from preliminary data. This will occur during the planning year of the program.

Can NIH provide references for the transition rate used in the power analysis? 

References used to arrive at the transition rate of approximately 46% for acute to chronic pain included Denk et al. (2014) Nat. Neuro. 17:192–200; Holley et al. (2017) Pain 158(5):794-801; Andersen et al. (2015) Pain 156(12):2413-22; and Meretoja et al. (2014) JAMA 311(1):90-92). Note this reference list is not all-inclusive. Applicants are encouraged to cite other references and/or their own unpublished results, provided that the scientific rationale is sound.

Are clinical trials allowed?

NIH staff do not anticipate that applications submitted to these FOAs will be clinical trials given that there is no proposed intervention.  Please see NIH’s guidelines regarding clinical trials here

Who should I include in the study population?

We anticipate that enrollment will reflect the population of the US in terms of sex and ethnic diversity.

What are some examples of candidate biomarkers that this study might include?

Candidate biomarkers could be in the areas of CNS imaging, patient reported outcomes, sensory testing, elements of the patient electronic health record, omics assays on biospecimens, or other well-justified areas. Examples of candidate biomarkers include patient reported psychosocial characteristics, targeted CNS changes, altered pain sensitivity and modulation, changes in the levels of a specific extracellular RNA species, protein, or metabolite, etc. 

Which patient reported outcomes and performance measures should I choose and how do I measure?

Patient reported outcomes (PROs) may be proposed as potential candidate biomarkers provided these are supported in the literature as indicators of transition from acute to chronic pain. Capturing performance assessment of cognitive, motor, and sensory function and self-reported assessment of emotional function may provide important biomarker data and for correlation with other collected biomarkers (i.e., imaging data).  Applicants may consider the use of PROMIS®, Neuro-QoL, and/or NIH Toolbox® measures to capture self-reports and performance assessment on dimensions of physical, mental and social health. 

What must my application have in order to be responsive to one of these RFAs? 

Please read the RFA you are applying to very carefully to ensure your application has the necessary components and justifications.

Could I propose to include more than one type of surgery or musculoskeletal pain cohort in my study?

Applicants should choose and justify a SINGLE type of surgery or musculoskeletal trauma.  The expected rate of transition across patients for the acute pain event in each cohort should be considered in the power analysis calculation, and patients should receive standard follow-up care. Please email Linda Porter with further questions.

Questions Generated from the Applicant Informational Webinar: 


A2CPS General Application Questions (for RFA specific questions see lower on the page.)

Abbreviations used below:

A2CPS: Acute to Chronic Pain Signatures

MCC: Multisite Clinical Centers

CCC: Clinical Coordination Center

DIRC: Data Integration and Resource Center

ODGC: Omics Data Generation Centers


Can applicants apply to more than one RFA as a PI or as a component of a project? Can applicants submit to one or more of these RFAs and also submit investigator-initiated or other types of NIH applications?

Yes, provided percent effort from the PI is sufficient to oversee each RFA or project.

I am a pain researcher who’s not doing clinical research and would be interested in being a part of a larger group of PIs on an application, could you facilitate making these connections?

Unfortunately, NIH staff cannot facilitate this.  However, PIs are welcome to network to find other researchers interested in collaboration.  Additionally, PIs may consider contacting their local CTSA and conducting PubMed or NIH Reporter searches to find other researchers with relevant expertise.

Do you have some idea how many awards you are making for each RFA?

We are making one award for every RFA, except for the ODGCs, which could have more than one award.

Is a letter of intent required?

A letter of intent is desired, but not required.  Letters of intent are helpful for NIH staff, as they allow us to better manage the workload involved in reviewing applications.  They also help program staff try to ensure that your application will be responsive to the RFA.

Do applicants to these RFAs need to fill our human subjects sections and biohazard sections?

Yes, if the applicants use human subjects and biohazards.

For the budget, is the dollar amount listed on the FOA direct only, or direct plus indirect?

The budget listed on the FOA is total cost for that FOA only, so indirect plus direct.  Please note that the planning year will have a lower budget than the other years.  Budget will be scaled up if the milestones from the planning year are met.

How was the budget determined?

The cost estimate for all FOAs is based on gathered data and consultation from several different academic centers.  Based on this, it was determined that imaging studies could be done with only one hour of imaging at each time point.  We also used average costs for various omics assays. Costs were multiplied by the number of patients in the cohort and by the number of times patients were imaged.  Average indirect costs were estimated. 

In terms of the 10+ proposed biomarkers, how specific do we need to be? For example, should we propose a single gene, a single measure from a single brain region, etc.?

Applicants should be very specific.  The reviewers will likely care about the justification of proposed biomarkers, so we encourage you to pick specific biomarkers, such as a single patient reported outcome, metabolite, protein, etc.  with strong evidence suggesting a link to pain.

Would imaging quality assessment happen at the data collection site?

Yes, there would be a standard protocol for imaging with data quality assessment at the collection site. This protocol will be finalized in the planning year.

Who will coordinate data quality for brain imaging?

The protocol for performance of imaging will be worked out by the consortium in the planning year with standards agreed upon by the consortium, and quality assessments will be done at collection site.

MCC Specific Questions

The MCC FOAs suggest that 50% of subjects should be enrolled and complete 6 months by 1 year. This means the first 6 months would need 50% enrollment. How tight is that schedule and can it be modified?

There is limited flexibility in the schedule that will be finalized at the kickoff meeting and in the planning year. However, the MCCs were specifically designed to be multi-site so that enrollment can be large.  Applicants need to consider recruitment and enrollment strategies carefully to ensure they will be able to meet these milestones and should provide evidence in their applications that they can be met.

How would you approach realistic rates of 15% transition for some pain conditions?

A pain condition with a lower rate of transition from acute to chronic pain would require more patients to be powered appropriately. As a cautionary note, if you choose a condition with a low transition rate, then the budget required may exceed the budgetary maximum of this study. Additionally, an under powered study may not fare well in review.

Will a single grant with multiple centers will be funded or will individual applications be brought together to work on one surgical cohort? 

MCCs will be one award to a PI or a group of PIs, and the clinical sites will be gathered under the umbrella of that center.  One award will go to that center, which will include multiple sites where patients will be enrolled and where the study will be done.

Would NIH consider revising their sample size of 1800 subjects with a single injury type in 2 years?

The planned study size is based on a power analysis from estimates of percent of individuals predicted to transition to chronic pain.  The power analysis also assumes that potential biomarkers have a low predictive value and are variable between patients.  This is merely an estimate, and power analyses submitted in applications may project a different patient number based on the proposed injury and known transition rates.  However, a larger cohort may cause the project to go over budget.  PIs may consider pain conditions that have higher transition rates but must strongly justify how many patients they think they will need to conduct the study.

If our cohort is smaller than 1800, then do we develop collaborations for the submission to achieve a full 1800 patient cohort before submitting, or can this happen during the planning year?

The cohort size should be chosen based on your power analysis. Depending on your transition rate it may be less than 1800 patients—this number is an estimate. The actual number will be based on the pain condition you are studying and the transition rate to chronic pain for that acute pain. You need to be able to recruit enough patients so that the study will be appropriately powered. If you are not able to recruit and enroll adequate numbers of patients, then yes, you should establish collaborations to ensure this before submitting your application.

How do you eliminate previous drug dependence and similar confounds?

These will likely be complex patients, and we expect that care will be standard care and recorded so that records can help us sort out how variability can contribute to different outcomes. Many patients will have multiple comorbidities.  These are things to consider in your application- note how you will manage this.  This can also be discussed during the planning year. 

For the MCC, are the timepoints for data collection fixed?

The timepoints were very carefully considered by NIH staff and outside experts.  There may be some flexibility (especially for t=0 for musculoskeletal pain), but we felt it was important to collect a baseline.  The 3 and 6-month time points were selected based on the literature for detecting physiological changes.  6 months is considered a transition point to chronic pain based on the literature and NIH’s consultation with outside experts.  Justification would need to be strong to convince a review panel that these numbers are not valid.

Can we argue that more time points are necessary?

Yes, you can try to justify this if you wish.  Consider that resources for phenotyping at the additional time points would need to come from outside of the budget NIH has set aside for this study.  You will also need to discuss this with the consortium and consider the agreed-upon clinical protocols.

How similar should the types of surgery or pain events be?

Surgeries must have similar procedures, and the prevalence of conversion from acute to chronic pain must be similar enough to meet the needs of the power analysis.  The study population must be such that the rate of variance and variability in the study is reasonably low.  The cohort must be homogenous enough with respect to pain events that the predictive value of the biomarkers we’re collecting would be applicable to other, similar cohorts.

For the MCC, there may be a tradeoff between homogeneity of the cohort and rapidity of enrollment.  Which factor should be given greater weight/importance?

Based on expert advice, the homogeneity of the cohort should be given primary weight.  We understand that this is an ambitious timeline, but as this is expected to involve multiple sites enrolling patients with common surgeries/injuries, this is likely feasible. 

Since MCCs will be multisite, do the subcontracts need to be finalized/executed at the time of submission or can these be finalized during the planning year?

Applicants likely will not have enough time to get subcontracts in place before the application due date. They should have very strong letters of support in their applications, so the reviewers can judge their application. Any notice of award will make it clear that these subcontracts need to be established. Because these will be cooperative agreements with considerable NIH involvement, if there is a problem getting subcontracts in place after the award is made there can be budget adjustments and/or award terminations if necessary. The subcontracts need to be in place as soon as possible.

For the MCC, can sites decide to collect additional measures or biospecimens for questions of interest that are outside of the consortium?

Yes, but this would not be accounted for in the budget for these awards.

Do all participants need to undergo brain imaging at each timepoint or can judicious selections be made for subsets of participants that will be imaged?

The expectation is that all patients will be imaged at all three timepoints, as our budget estimates were set based on this.  We want a large cohort, and imaging is a large part of this based on input from outside experts.

Can the brain imaging be done at multiple different sites under each MCC?

We expect that brain imaging would be done at the clinical site where the patient is enrolled, but would allow a little flexibility if it doesn’t affect patient retention.

Since the MCC is only doing data collection, should the grant submission include planned analyses?

MCC is doing data collection and patient care, but the PIs in the consortium will all work together to analyze data in the end- the DIRC won’t do the final data analysis in a vacuum.  MCC applicants can propose some resources towards this, but they are not responsible for the entirety of data analysis.

Can and how do pediatric studies fit into these funding announcements and opportunities?

This initial study is collecting data applicable to a broad population, so special populations such as pediatric populations are less applicable to this RFA. 

Is there a preference to have the MCCs at different locations, or can we apply for both MCC FOAs?

Applicants can apply to both the surgical and musculoskeletal MCCs, but should consider that these are large, complex studies that will need many different clinical sites to recruit and enroll the necessary number of patients.  Applicants should ensure that PI time commitment is sufficient to run both studies.

Would proposing a clinical trial detract from the responsiveness to the MCC RFA?

Applicants would be adding an intervention on top of a longitudinal study, which could change the outcome of the patients’ progression, complicate the study, and possibly detract from the overall application score. 

What type of fractures and what type of thoracotomy were considered as possible acute trauma?

 NIH is not being prescriptive about this.  PIs are responsible for selecting and justifying the type of surgery or musculoskeletal trauma.  We are looking for pain conditions with a high rate of homogeneity.

Must all the peri-operative subjects come from the MCC or can the MCC also recruit from other sites?

The MCC is meant to be multisite, so the MCC can recruit from other sites. 

For peri-surgical pain data collection FOA, it is likely that data collection will occur at multiple sites. Do you see having one primary site & the lead site writing the proposal? Or will the proposal come from multiple PIs with each site PI being multi-PI?

The MCC is intended to be a multisite clinical center.  We expect that there will be a proposal from one PI or a group of PIs from, for example, a large academic center.  This will engage clinical sites that could be within the purview of the academic center or beyond.  We don’t expect that one clinical site could accommodate the large cohort of approximately 1800. 

Is breast cancer surgery an acceptable pain condition?

No, because we want this study to apply to a broad population- women may have different risk factors than men, and this study is geared towards globally analyzing both men and women.  A breast cancer study would be unlikely to do well in review, given the goals of this study.

Are musculoskeletal trauma patients expected to be non-operatively managed?

Not necessarily.  Any interventions should be justified - the key is consistency across the musculoskeletal cohorts.

For the musculoskeletal pain MCC, how close in time to the injury must the time 0 assessment need to be in order to be responsive to the RFA?

This will need to be justified by the applicant.  Applicants should avoid straying too far from t=0, because biological changes might begin shortly after the pain event.  To obtain a reliable baseline, applicants are encouraged to set t=0 as closely as possible to the onset of the acute pain condition.

For musculoskeletal trauma, would fracture of different bones or polytrauma fit the single injury requirement?

The applicant needs to justify that the prevalence rate in the population is similar.  Polytrauma may create unnecessary confusion.  If an applicant proposes a polytrauma pain condition, then it must be strongly justified, as the study should be relatively homogenous to reduce variability.


DIRC-Specific Questions:

Will the DIRC extract materials from samples?

The DIRC only deals with information and data and will not extract materials from samples in any way.  Samples will be collected by the MCCs.  The DIRC will track which center has which biosamples.  The MCCs will send samples to the appropriate ODGC, which would perform extraction of material if needed.  During the kickoff meeting, the consortium will decide the potential biomarkers to be measured, and what, if any, special isolation methods, storage materials, etc., need to be employed. Those will be finalized and standardized in the planning year.

Doesn’t the proposal for the DIRC depend on what biomarkers are selected?  How does one put together a submission for the DIRC without knowing what measures are selected?

Based on a survey of the literature, we have concluded that biomarkers will most likely be in 5 areas (patient assessments, patient reported outcomes, sensory testing, imaging, and omics).  Applicants should exhibit the ability to handle data in these 5 areas and discuss how they can be flexible and how they would handle changes should they occur.


ODGC-Specific Questions

Is the microbiome included among the biomarkers?

It is not included as one of the things we pointed to for the ODGCs, but you can propose it under “other omics assays” in your ODGC application.  You will need to justify including this as a potential pain biomarker to the reviewers.

Can our application to the ODGC RFA include genomics?

 Applicants may propose other assays in addition to metabolomics, lipidomics, proteomics, and extracellular RNA. However, this study is not powered for a genome-wide association study and is not budgeted for whole-genome sequencing.

Will sample handling be performed by the ODGCs individually, or will one group be responsible for handling/tracking all samples?

The MCCs will collect and store biosamples, and the DIRC will set up a virtual biorepository.  The DIRC will keep track of who has what samples and will be responsible for devising a way for MCC groups to send biosamples to the ODGC groups.

Is it possible to outsource multi-omics assays and analysis (i.e. pay for other companies to perform the assays and analysis)?

Yes, you can propose this.  However, applicants should ensure that the outside parties are able to meet the needs of the consortium.

For the variant genotyping, should DNA isolation be included in the ODGC budgets?



This page last reviewed on October 30, 2018