Biomarkers Used as Outcomes: FDA Wants to Hear More on Examples
Posted 26 September 2016 | By Zachary Brennan
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.
Background
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 Area | Biomarker |
|---|
| Anesthesiology | T1*; magnitude of T4/T1* ratio by acceleromyography |
|---|
| Cardiology | Blood pressure |
|---|
| Serum low-density lipoprotein (LDL-C) |
| Hematology | Hemoglobin |
|---|
| Platelet count |
| Ecarin clotting time; activated partial thromboplastin time; thrombin time; activated clotting time; plasma diluted thrombin time |
| Serum ferritin |
| Infectious Disease | Hepatitis C virus (HCV) RNA* |
|---|
| Human immunodeficiency virus (HIV)-1 RNA |
| Sputum culture conversion to negative |
| Parasite count resolution |
| Inborn Errors of Metabolism | White 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) |
| Hemoglobin |
| Plasma ammonia; plasma glutamine; and plasma citrulline |
| Splenic volume by magnetic resonance imaging (MRI) |
| Metabolism and Endocrinology | Body 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 |
| Nephrology | Hemoglobin |
|---|
| Serum sodium |
| Oncology | CD34 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*) |
| Ophthalmology | Anterior chamber cells |
|---|
| Intraocular pressure (IOP) |
| Vitreomacular adhesion (VMA) by optical coherency tomography |
| Pulmonology | Forced expiratory volume in one second (FEV1) |
|---|
| FVC |
| Respiratory distress syndrome (RDS) by chest X-ray and fraction of inspired oxygen (FiO2) |
| Rheumatology | Joint angle |
|---|
| Uric acid |
| Transplant | Biopsy-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