NIH HEAL, FDA, and Other Core Outcome Sets

CHAPTER SECTIONS

Real-World Evidence: Patient-Reported Outcomes (PROs)


Section 4

NIH HEAL, FDA, and Other Core Outcome Sets

Contributors

Core Outcome Sets

Variability in outcomes measures across clinical trials hinders between-trial comparisons and future evaluations of efficacy and effectiveness of interventions and treatments (Dworkin et al. 2005). Use of a standard set of outcome measures—or core outcome sets—can “facilitate the process of developing research protocols, encourage development of multicenter projects in which all participating facilities agree to include these measures, provide a basis for determining the treatment outcomes that constitute clinically important differences, permit pooling of data from different studies, and provide a basis for meaningful comparisons among treatments of the clinical importance of their outcomes” (Dworkin et al. 2005).

Core outcome sets have been developed for different domains to help standardize outcome reporting in clinical trials (see Table), and investigators of ePCTs should consider if any of these core outcome sets could be used to address their specific research question. Of note, the Helping to End Addiction Long-term Initiative, or NIH HEAL Initiative, has created core outcome sets to facilitate cross-study comparisons for pain, improve interoperability of findings for patient-reported outcomes, and compare results across trials. The HEAL core outcome sets were released in January 2020 and represent PROs that HEAL pain clinical trials are required to collect. The NIH Pragmatic Trials Collaboratory currently supports 6 pragmatic NIH Collaboratory Trials that are a part of the HEAL Initiative: the PRISM studies (Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing).

Table 1 shows core outcome sets for NIH HEAL, FDA, and others. Where possible, a link to a sample measure is provided as well as a link to the instructions.

Table 1. Core Outcome Sets by Indication, Domain, and PRO Measure

Outcome Set
 Core Outcome Domains Suggested PRO Measures (with links to samples)
 Measure Instructions
NIH HEAL Initiative CDE for adult acute pain Pain intensity, pain interference, physical functioning/QOL, sleep, pain catastrophizing, depression, anxiety, global satisfaction with treatment, substance use screener
NIH HEAL Initiative CDE for adult chronic pain Pain intensity, pain interference, physical functioning/QOL, sleep, pain catastrophizing, depression, anxiety, global satisfaction with treatment, substance use screener
  • Pain, enjoyment, and general activity scale (PEG)
  • PROMIS Physical Functioning Short Form 6b
  • PROMIS Sleep Disturbance 6a + Sleep Duration Question
  • Pain Catastrophizing Scale – Short Form 6
  • PHQ-2
  • GAD-2
  • PGIC
  • TAPS 1
NIH HEAL Initiative CDE  for pediatric acute and chronic pain Child: Pain intensity, pain interference, physical functioning/QOL, sleep, pain catastrophizing, depression, anxiety, global satisfaction with treatment, substance use screener

Parent: pain catastrophizing, depression, anxiety

 Child:

  • BPI Short Form
  • Pediatric Quality of Life (PedsQL) Inventory
  • Adolescent Wake Sleep Scale + Sleep duration items
  • Pain Catastrophizing Scale for Children
  • PHQ-2
  • GAD-2
  • PGIC
  • National Institute on Drug Abuse (NIDA) Modified ASSIST Tool - 2

Parent:

  • Pain Catastrophizing
  • PHQ-2
  • GAD-2
 Child:

Parent:
NIH HEAL Initiative Back Pain Consortium (BACPAC) Minimum Dataset Pain intensity, pain interference, physical function/QOL, sleep, pain catastrophizing, depression, anxiety, global satisfaction with treatment, substance use screener, pain location, widespread pain, chronic lower back pain, opioid use
  • PEG Scale
  • PROMIS Physical Functioning Short Form 6b
  • PROMIS Sleep Disturbance 6a + Sleep Duration Question
  • Pain Catastrophizing Scale – Short Form 6
  • PHQ-2
  • GAD-2
  • PGIC
  • TAPS 1
  • Abbreviated Pain Somatization Adapted from NIH Research Task Force Minimum Dataset
  • Pain location determined by Radicular Pain Questions Adapted from NIH Research Task Force Minimum Dataset
  • Chronic lower back pain: 2 Items (low-back pain duration and frequency) from NIH Research Task Force Minimum Dataset
  • Single-item current opioid use
 BACPAC dataset requirements and recommendations
An international multidisciplinary panel (Chiarotto et al. 2018) for nonspecific low-back pain Physical functioning, pain intensity, and health-related quality of life (HRQoL)

 
Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) (Dworkin et al. 2005): Chronic pain Pain, physical functioning, emotional functioning, participant ratings of improvement and satisfaction with treatment, symptoms and adverse events and participant disposition
  • Numerical or categorical rating scale of pain intensity
  • Multidimensional Pain Inventory Interference Scale
  • BPI interference items
  • Beck's Depression Inventory
  • Profile of Mood States
  • PGIC
  • Symptoms and adverse events
  • Passive capture of spontaneously reported adverse events and symptoms and use of open-ended prompts
Veterans Health Administration Work Group (Kroenke et al. 2019): Musculoskeletal pain

 

 Pain intensity

Pain interference
  • Single-item numerical rating scale
  • BPI interference scale
 The Brief Pain Inventory User Guide
The U.S. Government, including individuals from the Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, and the U.S. Food and Drug Administration (Kluetz et al. 2016) developed these common measures for cancer. Symptomatic adverse events, physical function, disease-related symptoms
The Center for Medical Technology Policy (CMTP) (Basch et al. 2012): cancer Symptoms, HRQoL  

 

 

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SECTIONS

CHAPTER SECTIONS

sections

  1. Introduction
  2. How Are PRO Measures Used?
  3. Best Practices for Collecting PRO Measures in Pragmatic Clinical Trials
  4. NIH HEAL, FDA, and Other Core Outcome Sets
  5. Choosing PRO Measures
  6. Cultural Adaptation and Linguistic Translation
  7. Case Study From Guiding Good Choices for Health
  8. Incorporating PRO Data Into the EHR
  9. Patient-Focused Drug Development
  10. Additional Resources

Resources

HEAL Cooperative Agreement Presentation at 2020 PRISM Onboarding Meeting

 

REFERENCES

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Basch E, Abernethy AP, Mullins CD, et al. 2012. Recommendations for incorporating patient-reported outcomes into clinical comparative effectiveness research in adult oncology. J Clin Oncol. 30(34):4249-4255. doi:10.1200/JCO.2012.42.5967. PMID: 23071244.

Chiarotto A, Boers M, Deyo RA, et al. 2018. Core outcome measurement instruments for clinical trials in nonspecific low back pain. Pain. 159(3):481-495. doi:10.1097/j.pain.0000000000001117. PMID: 29194127.

Dworkin RH, Turk DC, Farrar JT, et al. 2005. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 113(1):9–19. doi:10.1016/j.pain.2004.09.012. PMID: 15621359.

 

Kluetz PG, Slagle A, Papadopoulos EJ, et al. 2016. Focusing on core patient-reported outcomes in cancer clinical trials: symptomatic adverse events, physical function, and disease-related symptoms. Clin Cancer Res. 22(7):1553-1558. doi:10.1158/1078-0432.CCR-15-2035. PMID: 26758559.

Kroenke K, Krebs EE, Turk D, et al. 2019. Core outcome measures for chronic musculoskeletal pain research: recommendations from a Veterans Health Administration Work Group. Pain Med. 20(8):1500-1508. doi:10.1093/pm/pny279. PMID: 30615172.

Kroenke K, Spitzer RL, Williams JB. 2001. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 16(9):606-613. doi:10.1046/j.1525-1497.2001.016009606.x. PMID: 11556941.

 

 

 


Version History

September 14, 2022: Updated as part of annual update (changes made by K Staman).

Published May 30, 2020

Updated November 17, 2020: Moved the Common Data Elements to a new section (changes made by K Staman).

current section :

NIH HEAL, FDA, and Other Core Outcome Sets

  1. Introduction
  2. How Are PRO Measures Used?
  3. Best Practices for Collecting PRO Measures in Pragmatic Clinical Trials
  4. NIH HEAL, FDA, and Other Core Outcome Sets
  5. Choosing PRO Measures
  6. Cultural Adaptation and Linguistic Translation
  7. Case Study From Guiding Good Choices for Health
  8. Incorporating PRO Data Into the EHR
  9. Patient-Focused Drug Development
  10. Additional Resources

Citation:

Zigler C, DeBar L, Weinfurt K. Real-World Evidence: Patient-Reported Outcomes (PROs): NIH HEAL, FDA, and Other Core Outcome Sets. In: Rethinking Clinical Trials: A Living Textbook of Pragmatic Clinical Trials. Bethesda, MD: NIH Pragmatic Trials Collaboratory. Available at: https://rethinkingclinicaltrials.org/chapters/conduct/real-world-evidence-patient-reported-outcomes-pros/nih-heal-fda-and-other-core-outcome-sets/. Updated March 6, 2026. DOI: 10.28929/195.