Biomarkers Used as Outcomes: FDA Wants to Hear More on Examples

Regulatory NewsRegulatory News | 26 September 2016 |  By 

The US Food and Drug Administration (FDA) is seeking comment from interested stakeholders to determine the utility of a list of examples of biomarkers used as outcomes in development of FDA-approved new molecular entities and new biological therapeutics.

The comments, which should be submitted by 18 November, may assist FDA in developing databases on biomarkers for drug development in the future, the agency said.


Biomarkers are frequently used in support of drug development, particularly as an outcome in a clinical trial.

FDA offers a look at biomarkers used in 12 therapeutic areas – including cardiology, oncology and infectious disease – that were accepted and used as outcomes in clinical trials as the basis for drug and biologic approvals from October 2007 to December 2015.  

Therapeutic AreaBiomarker
AnesthesiologyT1*; magnitude of T4/T1* ratio by acceleromyography
CardiologyBlood pressure
Serum low-density lipoprotein (LDL-C)
Platelet count
Ecarin clotting time; activated partial thromboplastin time; thrombin time; activated clotting time; plasma diluted thrombin time
Serum ferritin
Infectious DiseaseHepatitis C virus (HCV) RNA*
Human immunodeficiency virus (HIV)-1 RNA
Sputum culture conversion to negative
Parasite count resolution
Inborn Errors of MetabolismWhite blood cell count; neutrophil count; red blood cell count; mean corpuscular volume
Growth in height or weight
Serum LDL-C
Blood phenylalanine
Forced vital capacity (FVC)
Plasma ammonia; plasma glutamine; and plasma citrulline
Splenic volume by magnetic resonance imaging (MRI)
Metabolism and EndocrinologyBody weight
Bone mineral density by DEXA* scan
Hemoglobin A1c*
Serum calcium; oral calcium supplements; oral vitamin D supplements
Serum LDL-C
Urinary free cortisol (UFC)
Vertebral fractures by X-ray
Visceral adipose tissue (VAT) by computed tomography (CT) scan
Serum sodium
OncologyCD34 positive cell count
Complete blood count (e.g., absolute neutrophil count)
Tumor burden by Bcr-Abl* (Philadelphia chromosome)
Tumor burden by Philadelphia chromosome positive cells
Plasma methotrexate
Splenic volume
Serum asparaginase
Serum testosterone
Tumor burden by imaging (using criteria such as RECIST* or EBMT*)
OphthalmologyAnterior chamber cells
Intraocular pressure (IOP)
Vitreomacular adhesion (VMA) by optical coherency tomography
PulmonologyForced expiratory volume in one second (FEV1)
Respiratory distress syndrome (RDS) by chest X-ray and fraction of inspired oxygen (FiO2)
RheumatologyJoint angle
Uric acid
TransplantBiopsy-proven acute rejection (BPAR)
  • *T1: 1st twitch height
  • *T4/T1: Ratio of the 4th twitch height for train of four (four stimuli given at a frequency of 2 hertz eliciting four twitches) divided by the first twitch height
  • *RNA: Ribonucleic acid
  • *Hemoglobin A1C: Glycosylated hemoglobin
  • *DEXA: Dual-energy X-ray absorptiometry (or bone densitometry)
  • *Bcr-Abl: A fusion oncogene between Break point cluster (Bcr) gene at chromosome 22 and Abelson (Abl) tyrosine kinase gene at chromosome 9
  • *RECIST: Response Evaluation Criteria in Solid Tumors
  • *EBMT: European Society for Blood and Marrow Transplantation response criteria

However, FDA notes that the appropriateness of the use of any particular biomarker as an outcome in one drug program should not be assumed to be appropriate for use in a different context or for a different drug development program. Therefore, drug sponsors are encouraged to consult with the relevant FDA review division as early as possible in drug development regarding the use of a particular biomarker in their planned clinical trials.

Call for Comments

FDA is now soliciting suggestions and comments to determine the utility of the biomarker outcomes list and to identify any areas where more information can be disseminated on biomarkers that have been used to support the approval of drugs or biologics. Specifically, FDA wants to hear about:

  • Areas of improvement for communicating and disseminating information about biomarkers and their utility as drug development tools
  • The best approach for updating the biomarkers outcomes list, including any modifications moving forward

Federal Register


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