The Biomarkers Consortium – Developing Endpoints for Clinical Trials in CABP and Skin Infections developed a set of recommendations to help FDA establish efficacy outcome measures (i.e., endpoints) for clinical trials of investigational agents to treat community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). The endpoint recommendations are tied to historical data in each indication, thereby providing the basis for sound non-inferiority (NI) trial design and NI margin justification. A second key deliverable of the project was to create a Patient-Reported Outcome (PRO) instrument for CABP and ABSSSI that accurately measures the symptoms of each indication. This instrument will enable clinical trialists to assess how a patient feels, functions and survives in anti-infective clinical trials and studies.
- Develop reliable and well-defined clinically relevant endpoints for clinical trials of antibiotics for treatment of CABP and ABSSSI, two common and serious bacterial infections.
- Complete the content validity phase of a PRO measure for each of the ABSSI and CABP indications.
Results & Accomplishments
Developed Novel Outcome Measures
The FNIH CABP/ABSSSI Project Team developed relevant outcome measures for CABP and ABSSSI via retrospective analyses and synthesis of data from clinical trials. The results of the project were submitted to the FDA and subsequently incorporated into FDA guidance to include symptomatic endpoints for CABP and ABSSSI. Six antibiotic drugs have been approved using the updated FDA guidance.
- National Institute of Allergy and Infectious Diseases (NIAID)
- U.S. Food and Drug Administration (FDA)
- Actelion Pharmaceuticals Ltd.*
- American Thoracic Society
- AstraZeneca Pharmaceuticals LP*
- Basilea Pharmaceutica International Ltd.*
- Cempra Pharmaceuticals*
- Cerexa, Inc.*
- Cubist Pharmaceuticals, Inc.*
- Durata Therapeutics, Inc.*
- ICON plc.
- Infectious Diseases Society of America
- Janssen, L.P.*
- The Medicines Company*
- Merck Sharp & Dohme Corp.*
- Nabriva Therapeutics AG*
- Trius Therapeutics, Inc.*
- Pfizer Inc*
- Pharmaceutical Research and Manufacturers of America*
- Theravance BioPharma*
*Provided financial or in-kind support for this program.
Steve Hoffmann, Associate Vice President, Research Partnerships, [email protected]
Developed Patient-Reported Outcomes (PRO)
- The FNIH CABP/ABSSSI Project Team developed two PRO instruments – PNEUMO PRO© for and CABP or HABP indications, and SKINFECT PRO© for ABSSSI indication. The PRO instruments were developed in accordance with the FDA Guidance for PRO measures (2009), and are intended to measure tangible benefits for patients in clinical trials of antibacterial drugs for CABP, HABP and ABSSSI to measure how patients with these conditions feel, function, and survive.
- PNEUMO PRO© https://eprovide.mapi-trust.org/instruments/community-acquired-bacterial-pneumonia-symptom-diary
- SKINFECT PRO© https://eprovide.mapi-trust.org/instruments/acute-bacterial-skin-and-skin-structure-infections-symptom-diary
- Final Report for development of PNEUMO PRO here
- Final Report for the development of SKINFECT PRO here
- Development of a Patient-Reported Outcome instrument (SKINFECT-PRO) to standardize and quality symptoms of Acute Bacterial Skin and Skin Structure Infections (ABSSSI). Powers JH, Howard K, Saretsky T, Clifford S, Hoffmann SC, Talbot GH, Cimms TA, Llorens L, FNIH Biomarkers Consortium CABP ABSSSI Project Team. Presented at ISPOR 20th Annual International Meeting May 1620, 2015, Philadelphia, PA.
- Community-Acquired Bacterial Pneumonia (CABP): Development of a new Patient-Reported Outcome (PRO) Measure. Howard K, Clifford S, Powers JH, Saretsky TL, Hoffmann SC, Llorens L, Talbot GH, Cimms TA, FNIH Biomarkers Consortium CABP ABSSSI Project Team. Presented at ISPOR 20th Annual International Meeting May 1620, 2015, Philadelphia, PA.
Resulting FDA Guidance Documents
- Guidance for Industry: Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for Treatment. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research.
- Draft Guidance for Industry: Community-Acquired Bacterial Pneumonia: Developing Drugs for Treatment. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research.
- Understanding Early and Late Endpoints in Registrational Trials of Community-acquired Bacterial Pneumonia. Talbot G. Clin Infect Dis. 2021 Nov 2;73(9):e2613-e2615. doi: 10.1093/cid/ciaa853. PMID 32584958
- Patient-Reported Outcome Assessments as Endpoints in Studies in Infectious Diseases. Powers JH, Howard K, Saretsky T, Clifford S, Hoffmann S, Llorens L, Talbot G. Clin Infect Dis. 2016 Aug 15;63 Suppl 2:S52-6. doi: 10.1093/cid/ciw317. PMID: 27481954
- Developing Outcomes Assessments as Endpoints for Registrational Clinical Trials of Antibacterial Drugs: 2015 Update From the Biomarkers Consortium of the Foundation for the National Institutes of Health. Talbot GH, Powers JH, Hoffmann SC; Biomarkers Consortium of the Foundation for the National Institutes of Health CABP-ABSSSI and HABP-VABP Project Teams. Clin Infect Dis. 2016 Mar 1;62(5):603-7. doi: 10.1093/cid/civ927. PMID: 26668337
- Progress on developing endpoints for registrational clinical trials of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections: update from the Biomarkers Consortium of the Foundation for the National Institutes of Health. Talbot GH, Powers JH, Fleming TR, Siuciak JA, Bradley J, Boucher H; CABP-ABSSSI Project Team. Clin Infect Dis. 2012 Oct;55(8):1114-21. Review. PMID: 22744885
- Editorial Commentary: A Collaborative Model for Endpoint Development: Advancing the Science of Antibacterial Drug Clinical Trials. Toerner JG, Cox E. Clin Infect Dis. 2016 Mar 1;62(5):608-9. doi: 10.1093/cid/civ1007.
- A collaborative model for endpoint development for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Toerner JG, Burke L, Komo S, Papadopoulos E. Clin Infect Dis. 2012 Oct;55(8):1122-3.
- ICON Press Release (Feb. 20, 2017): ICON Selected by the FDA to Validate Patient-Reported Outcome Endpoints for Antibacterial Drug Trials