Drugs

Table of Surrogate Endpoints That Were the Basis of Drug Approval or Licensure

Downloadable Table of Surrogate Endpoints (XLS-38KB)

What is the purpose of the Surrogate Endpoint Table?

FDA’s surrogate endpoint table provides valuable information for drug developers on endpoints that may be considered and discussed with FDA for individual development programs. This table also fulfills a 21st Century Cures Act requirement to publish a list of “surrogate endpoints which were the basis of approval or licensure (as applicable) of a drug or a biological product” under both accelerated and traditional approval pathways.

Section 3011 of the 21st Century Cures Act established section 507 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), which mandates that the FDA publish a list of “surrogate endpoints which were the basis of approval or licensure (as applicable) of a drug or biological product” under both accelerated and traditional approval provisions. The Surrogate Endpoint Table below fulfils this legislative requirement and is intended to provide valuable information for drug developers on endpoints that may be considered and discussed with FDA for individual development programs.

According to section 507(e)(9) of the FD&C Act “[t]he term ‘surrogate endpoint’ means a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure, that is not itself a direct measurement of clinical benefit, and—

‘‘(A) is known to predict clinical benefit and could be used to support traditional approval of a drug or biological product; or

‘‘(B) is reasonably likely to predict clinical benefit and could be used to support the accelerated approval of a drug or biological product in accordance with section 506(c).’’

This surrogate endpoint table includes surrogate endpoints that sponsors have used as primary efficacy clinical trial endpoints for approval of new drug applications (NDAs) or biologics license applications (BLAs).  The table also includes surrogate endpoints that may be appropriate for use as a primary efficacy clinical trial endpoint for drug or biologic approval, although they have not yet been used to support an approved NDA or BLA. We believe that this list should facilitate consideration of potential surrogate endpoints when developers are designing their drug development programs. 

What are the key considerations of the surrogate endpoint table?

  • The table is intended to serve as a reference guide to help inform discussion of potential surrogate endpoints with relevant Center for Biologics Evaluation and Research (CBER) or Center for Drug Evaluation and Research (CDER) review divisions, with the intended goal of facilitating product development.
  • The acceptability of these surrogate endpoints for use in a particular drug or biologic development program will be determined on a case-by-case basis. It is context dependent, relying in part on the disease, studied patient population, therapeutic mechanism of action, and availability of current treatments. A particular surrogate endpoint that may be appropriate for use in a particular drug or biologic clinical development program, should not be assumed to be appropriate for use in a different program that is in a different clinical setting.
  • The table does not include composite endpoints that are a combination of biomarker surrogate endpoints and clinical endpoints.  Likewise, composite endpoints of biomarker surrogate endpoints and clinical outcome assessments are also not included.  If a composite endpoint was composed of multiple biomarker surrogate endpoints, that information is included on the table.   
  • Separate adult and pediatric sections are provided.  Pharmacokinetic endpoints that have supported extrapolation from adults to children are not included in the pediatric section.  
  • If a surrogate endpoint was previously used to support accelerated approval of a drug or biologic but subsequent confirmatory trials failed to demonstrate the expected clinical benefit, the surrogate endpoint would no longer be accepted for this use and it was not included on the table.

What are the table’s limitations?

  • This table reflects surrogate endpoints that have either been already used in development programs for drugs that have been approved, or surrogate endpoints that FDA has indicated acceptance of in guidances or other documents.  FDA encourages development of novel surrogate endpoints, and strongly encourages sponsors to seek advice from the relevant CBER or CDER division of such novel endpoints early in development by scheduling a PDUFA VI Type C SE meeting to discuss the use of a novel surrogate endpoint in their planned clinical trials. The acceptability of a surrogate endpoint for an individual drug or biologic development program will be determined on a case by case basis.
  • The Surrogate Endpoint Table is not a replacement for discussions with appropriate CBER or CDER review divisions.  Sponsors are reminded that surrogate endpoints provided in this table are intended to facilitate but not replace discussions of individual drug development programs between the sponsor and the appropriate review division.
  • The table does not include surrogate endpoints that may have been accepted for past programs but are no longer acceptable as an endpoint to support registration.  As scientific understanding, clinical information, and technology evolve, a previously used surrogate endpoint may no longer be considered sufficiently robust or appropriate for use in current programs.   

The SE table was last updated July 23, 2018 and will be updated by CBER and CDER every 6 months to reflect current thinking as mandated by section 507 of the FD&C Act.

Footnotes

# Surrogate endpoint is part of a composite of biomarker surrogate endpoints.

* Mechanism agnostic refers to cases where there are many mechanisms of action associated with a surrogate endpoint, so it is not directly related to a particular causal pathway.

§ Endpoints based on changes in tumor burden may be used for both traditional and accelerated approval depending on context of use, including factors such as disease, effect size, effect duration, residual uncertainty and benefits of other available therapy.

˟ The agency anticipates that this surrogate endpoint could be appropriate for use as a primary efficacy clinical trial endpoint for drug or biologic approval, although it has not yet been used to support an approved NDA or BLA.

¤ Bone mineral density is an acceptable primary endpoint for establishing efficacy for the treatment of male or glucocorticoid-induced osteoporosis after efficacy based on new morphometric vertebral fractures has been established in postmenopausal women.    

Downloadable Table of Surrogate Endpoints (XLS-38KB)

Adult Surrogate Endpoint Table

Disease or Use Patient Population Surrogate endpoint Type of approval appropriate for Drug mechanism of action 
 Alpha-1-antitrypsin deficiencyPatients with congenital alpha-1 antitrypsin deficiencyPlasma alpha-1 proteinase inhibitorTraditionalAlpha-1 protease inhibitor augmentation
Acetylglutamate Synthase deficiencyPatients with hyperammonemia due to N-acetylglutamate synthase deficiencyPlasma ammonia TraditionalCarbamoyl Phosphate Synthetase 1 (CPS 1) activator
Acromegaly Patients with acromegaly who don't respond to or cannot undergo other standard therapiesSerum Insulin-like growth factor-I (IGF-1)TraditionalGrowth hormone receptor antagonist
Acromegaly Patients with acromegaly who don't respond to or cannot undergo other standard therapiesSerum growth hormone and serum insulin-like growth factor-I  (IGF-1) TraditionalSomatostatin analog
Acute BronchospasmPatients with acute bronchospasm associated with reversible obstructive airway disease or exerciseForced expiratory volume in 1 second (FEV1)Traditional Beta-2 adrenergic agonist
Anthrax vaccinePatients at high risk of exposure to anthraxAnti-protective antigen antibody responseTraditionalInduction of immunity
AsthmaPatients with asthmaForced expiratory volume in 1 second (FEV1)  Traditional Corticosteroid; Beta-2 adrenergic agonist
Benign hematologyPatients with Thrombocytopenia due to immune (idiopathic) thrombocytopenia or chronic hepatitis CPlatelet count responseTraditional Mechanism agnostic*
Benign hematologyPatients with chronic iron overload or non-transfusion-dependent thalassemia syndromesSerum ferritin and liver iron concentration Accelerated Iron chelator
Benign hematologyPatients with anemia due to (1) chronic kidney disease, (2) chemotherapy-induced anemia, (3) zidoviduine in patients with HIV-infection.Hematologic response and reduction in transfusionTraditionalMechanism agnostic*
Benign hematologyPatients with Severe Aplastic AnemiaHematologic response TraditionalMechanism agnostic*
Benign hematologyPatients with venous thromboembolism (VTE)/pulmonary embolismTotal venous thromboembolism and all-cause death#TraditionalAnticoagulant
Cancer: hematological malignancies Patients with Acute Lymphoblastic Leukemia Serum asparaginase Traditional Asparagine-specific enzyme
Cancer: hematological malignancies Patients with diffuse large B-cell lymphomaEvent-free survival (EFS) ˟TraditionalMechanism agnostic*
Cancer: hematological malignancies Patients with chronic myeloid leukemia; hypereosinophilic syndrome/chronic eosinophilic leukemia Major hematologic responseAccelerated/Traditional§ Mechanism agnostic*
Cancer: hematological malignancies Patients with acute myeloid leukemia and acute lymphoblastic leukemiaDurable complete remission rateAccelerated/Traditional§ Mechanism agnostic*
Cancer: hematological malignancies Patients with acute lymphoblastic leukemia; myelodysplastic/myeloproliferative diseases; chronic myeloid leukemiaMajor hematologic response and cytogenic responseAccelerated/Traditional§ Mechanism agnostic*
Cancer: hematological malignancies Patients with B-cell precursor acute lymphoblastic leukemia in first or second complete remissionMinimal residual disease response rate AcceleratedMechanism agnostic*
Cancer: hematological malignancies Patients with T-cell lymphoma;  mantle cell lymphoma; classical hodgkin lymphoma; anaplastic large cell lymphoma and mycosis fungoides; non-hodgkin’s lymphoma; multiple myeloma; chronic myeloid leukemia; acute lymphoblastic leukemia; small lymphocytic lymphoma; Waldenström’s macroglobulinemia; marginal zone lymphomaDurable objective overall response rate (ORR)Accelerated/Traditional§ Mechanism agnostic*
Cancer: hematological malignancies Patients with multiple myeloma; mantle cell lymphoma; classical Hodgkin lymphoma; follicular lymphoma; diffuse large B cell lymphoma; chronic myeloid leukemia; chronic lymphocytic leukemia ; cutaneous T cell lymphoma; all other Non-Hodgkin lymphoma Progression free survivial (PFS)TraditionalMechanism agnostic*
Cancer: solid tumorsPatients with breast cancer; ovarian cancer; renal cell carcinoma; pancreatic neuroendocrine cancer; colorectal cancer; head and neck cancer; non-small cell lung cancer; melanoma; tuberous sclerosis complex; merkel cell carcinoma; basal cell carcinoma; urothelial carcinoma; cervical cancer; endometrial cancer;  hepatocellular carcinoma; fallopian tube cancerDurable objective overall response rate (ORR)Accelerated/Traditional§ Mechanism agnostic*
Cancer: solid tumorsPatients with breast cancer; renal cell carcinoma; pancreatic neuroendocrine tumor; soft tissue sarcoma; ovarian, fallopian tube, or primary peritoneal cancer; prostate cancer; thyroid cancer; colorectal cancer; non-small cell lung cancer; head and neck cancer; uberous sclerosis complex; merkel cell carcinoma; basal cell carcinoma; urothelial carcinoma; cervical cancer; endometrial cancer;  hepatocellular carcinoma; fallopian tube cancer  Progression free survivial (PFS)Accelerated/Traditional§ Mechanism agnostic*
Cancer: solid tumorsPatients with surgically resected Dukes’ C colon cancer, melanoma, renal cell cancer or breast cancerDisease-free survival (DFS)Accelerated/Traditional§ Mechanism agnostic*
Cancer: solid tumorsPatients with breast cancer; neuroblastomaEvent-free survival (EFS) ˟Accelerated/Traditional§ Mechanism agnostic*
Cancer: solid tumorsPatients with breast cancerPathological complete responseAccelerated Mechanism agnostic*
Cancer: solid tumorsPatients with nonmetastatic castrate-resistant prostate cancerMetastasis-free survivalAccelerated/Traditional§ Mechanism agnostic*
Chronic kidney disease Patients with chronic kidney disease secondary to multiple etiologies Estimated glomerular filtration rate ˟ TraditionalMechanism agnostic*
Chronic kidney disease Patients with chronic kidney disease secondary to multiple etiologies Serum creatinine ˟TraditionalMechanism agnostic*
Chronic obstructive pulmonary disease (COPD)Patients with COPDForced expiratory volume in 1 second (FEV1)Traditional Long-acting beta2-adrenergic agonist; Anticholinergic; Phosphodiesterase 4 inhibitor
Cushing's disease Patients with Cushing’s disease Urine free cortisol  TraditionalSomatostatin analog 
Cushing's syndromePatients with endogenous Cushing’s syndromeUrine free cortisol ˟  Traditional  Cortisol synthesis inhibitor 
Cystic fibrosisPatients with cystic fibrosisForced expiratory volume in 1 second (FEV1)Traditional Cystic fibrosis transmembrane conductance regulator potentiator
CystinuriaPatients with cystinuriaUrinary cystineTraditionalReducing and complexing thiol
Cytomegalovirus (CMV) CMV seropositive and hematopoietic transplant recipients requiring prophylaxis  Plasma CMV-DNA exceeding threshold for starting treatment
 
TraditionalAntiviral
Diphtheria vaccinePatients to be immunized against diphtheria Diphtheria antitoxoid antibody responseTraditionalInduction of immunity
Duchenne muscular dystrophy (DMD)Patients with DMD who have a confirmed mutation of the DMD gene that is amenable to exon 51 skippingSkeletal muscle dystrophinAcceleratedAntisense oligonucleotide
Exocrine pancreatic insufficiencyPatients with exocrine pancreatic insufficiency due to cystic fibrosis, chronic pancreatitis, pancreatectomy, or other conditionsFecal coefficient of fat absorption TraditionalCombination of porcine-derived lipases, proteases, and amylases
Female hypogonadotropic
hypogonadism
Infertile women with hypogonadotropic hypogonadismFollicle size, serum estradiol and progesterone#TraditionalGonadotropin
First aid antiseptic; Health care antiseptic; Consumer antisepticGeneral public, consumers, and health care professionalsBacterial countTraditional and Monograph 
Antimicrobial 
GoutPatients with goutSerum uric acidTraditional Xanthine oxidase inhibitor; URAT1 inhibitor
Heart failurePatients with acute heart failure Blood pressureTraditionalVasodilator
Hepatitis A (Hep A) vaccinePatients to be immunized against Hep A Anti-Hep A virus antibody concentration TraditionalInduction of immunity
Hepatitis B (Hep B) vaccinePatients to be immunized against Hep BAnti-Hep B virus antibody concentrationTraditionalInduction of immunity
Hepatitis B Virus (HBV)Patients with HBV infection with or without cirrhosis Undetectable serum HBV-DNATraditional Antiviral
Hepatitis C Virus (HCV)Patients with HCV infection with or without cirrhosisSustained viral response (HCV-RNA) Traditional Antiviral 
Hepatorenal syndrome Patients with hepatorenal syndrome type 1Serum creatinine ˟TraditionalVasopressin analog
Homozygous sitosterolemia (phytosterolemia)Patients with homozygous sitosterolemia (phytosterolemia)Plasma sitosterol and campesterolTraditionalDietary cholesterol absorption inhibitor
Human Immunodeficiency Virus-1 (HIV-1)Patients with HIV-1Undetectable plasma HIV RNATraditionalAntiviral 
Human Immunodeficiency Virus-1 (HIV-1)Patients at high risk of sexually acquired HIV-1 Serum HIV antibody concentrationTraditionalAntiviral 
Human Immunodeficiency Virus-1 (HIV-1)Highly treatment-experienced  HIV-1 patients Greater than 0.5 log reduction in plasma HIV RNATraditionalAntiviral 
HypercholesterolemiaPatients with heterozygous familial and nonfamilial hypercholesterolemiaSerum LDL-CTraditionalLipid-lowering
Hypercholesterolemia Patients with homozygous familial hypercholesterolemiaSerum LDL-C TraditionalLipid-lowering 
Hyperkalemia Patients with hyperkalemiaSerum potassiumTraditionalPotassium binder
HyperphosphatemiaDialysis patients with hyperphosphatemia Serum phosphate TraditionalPhosphate binder; Sodium proton exchanger inhibitor
Hypertension Patients with hypertension Blood pressureTraditionalAngiotensin II receptor blocker; Dihydropyridine calcium channel blocker; Renin inhibitor; Aldosterone antagonist; Vasodilator; Dihydropyridine calcium channel blocker
HypertriglyceridemiaPatients with severe hypertriglyceridemiaSerum triglyceridesTraditional Lipid-lowering
Hypokalemia Patients with hypokalemiaSerum potassium TraditionalAldosterone antagonist
Hyponatremia Patients with hypervolemic and euvolemic hyponatremiaSerum sodiumTraditionalVasopressin receptor antagonist
HypotensionPatients with distributive shockBlood pressureTraditionalAlpha  and beta adrenergic agonist; Vasopressin analog
HypotensionPatients with symptomatic orthostatic hypotensionBlood pressureAcceleratedAlpha adrenergic agonist; Synthetic amino acid analog that is metabolized to norepinephrine
HypothyroidismPatients with hypothyroidismSerum thyroid-stimulating hormone (TSH)TraditionalThyroid hormone analog 
Idiopathic pulmonary fibrosis  Patients with idiopathic pulmonary fibrosisForced vital capacity (FVC)  Traditional Pyridone; Kinase inhibitor
Influenza vaccinePatients to be immunized against influenza  Hemagglutination inhibition antibody responseAcceleratedInduction of immunity
Interoperative hemorrhagePatients who require reduction of blood pressure to reduce bleeding during surgeryBlood pressureTraditionalVasodilator
Japanese encephalitis vaccinePatients to be immunized against Japanese encephalitis Neutralizing antibody responseTraditionalInduction of immunity
LipodystrophyPatients with congenital or acquired generalized lipodystrophySerum hemoglobin A1C, fasting glucose and triglycerides Traditional Leptin analog
Male hypogonadotropic hypogonadismMen with selected cases of hypogonadotropic hypogonadismSperm countTraditionalGonadotropin
Meningococcal vaccinePatients to be immunized against meningococcal meningitisSerum bactericidal antibody responseTraditionalInduction of immunity
Nephropathic cystinosisPatients with nephropathic cystinosisWhite blood cell cystine and serum creatinine#TraditionalCystine depleting agent
Nonalcoholic steatohepatitis (NASH)Precirrhotic NASH patients with liver fibrosisHistopathologic findings of either 1) resolution of steatohepatitis with no worsening of fibrosis OR 2) improvement of fibrosis with no worsening of steatohepatitis OR 3) Both#AcceleratedAnti-fibrotic; Anti-inflammatory
Opioid dependencePatients with opioid dependenceUrine toxicology test for opioidsTraditionalPartial opioid agonist
OsteoporosisPostmenopausal women with osteoporosisNew morphometric vertebral fracturesTraditionalEstrogen agonist/antagonist; Parathyroid hormone analog; Bisphosphonate; RANK ligand (RANKL) inhibitor
OsteoporosisPatients with glucocorticoid induced osteoporosisBone mineral density¤ TraditionalBisphosphonate; Parathyroid hormone analog
OsteoporosisMen with osteoporosisBone mineral density¤ Traditional Parathyroid hormone analog; Bisphosphonate; RANK ligand (RANKL) inhibitor
Paget's diseasePatients with Paget's diseaseSerum alkaline phosphataseTraditionalBisphosphonate
Peri-implantitisPatients with peri-implantitisProbing pocket depth ˟TraditionalAntimicrobial
PeriodontitisPatients with chronic periodontitis with a mean probing pocket depth of greater than 5mm Probing pocket depthTraditionalAntimicrobial
PhenylketonuriaPatients with hyperphenylalaninemia due to tetrahydrobiopterin-responsive phenylketonuriaPlasma phenylalanine TraditionalPhenylalanine hydroxylase activator
Pneumonia vaccinePatients ( ≥ 50 years of age) to be immunized against pneumonia and invasive diseaseOpsonophagocytic antibody responseAccelerated Induction of immunity
Polio vaccinePatients to be immunized against polio Neutralizing antibody responseTraditionalInduction of immunity
Polycystic kidney diseasePatients with autosomal dominant polycystic kidney disease with or without associated polycystic liver disease Total kidney volume ˟Accelerated Mechanism agnostic*
Preterm birthWomen with a singleton pregnancy who have a history of singleton spontaneous preterm birthDelivery prior to 37 weeks gestation˟Accelerated Progesterone analog
Primary biliary cholangitis Patients with primary biliary cholangitis Serum alkaline phosphatase and bilirubin#AcceleratedFarnesoid X receptor (FXR) agonist
Primary glomerular disease associated with nephrotic syndromePatients with primary glomerular disease associated with nephrotic syndrome  Proteinuria (urinary protein/creatinine ratio) ˟Accelerated Mechanism agnostic*
Primary hyperparathyroidism Patients with hypercalcemia due to primary hyperparathyroidism Serum calcium TraditionalCalcium-sensing receptor agonist
Primary immunoglobulin A nephropathyPatients with primary IgA NephropathyProteinurea (urinary protein/ creatinine ratio) ˟ Accelerated Mechanism agnostic*
Pulmonary multi-drug resistant tuberculosisPatients with pulmonary multi-drug resistant tuberculosisTime to sputum culture conversion to negativeAcceleratedAntimicrobial 
Pulmonary tuberculosis Patients with active or latent pulmonary tuberculosisTime to sputum culture conversion to negativeAcceleratedAntimicrobial 
Rabies immune globulinPatients with suspected exposure to a rabid animalRabies neutralizing activity and antibody responseTraditionalPassive immunity
Secondary hyperparathyroidism Patients with secondary hyperparathyroidism associated with chronic kidney disease Serum intact parathyroid hormone (iPTH)  TraditionalCalcium-sensing receptor agonist; Vitamin D3 analog
Supportive cancer carePatients with delayed methotrexate clearance due to impaired renal functionPlasma methotrexateTraditional Carboxypeptidase
Supportive cancer carePatients with  leukemia, lymphoma, and solid tumor malignancies who are receiving anti-cancer therapy expected to result in tumor lysis and subsequent elevation of uric acid.Serum uric acidTraditional Uric acid specific enzyme
Supportive cancer carePatients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs Duration of severe neutropenia Traditional Leukocyte growth factor
Testosterone deficiency Men with primary or hypogonadotropic hypogonadismSerum testosteroneTraditionalAndrogen
Tetanus vaccinePatients to be immunized against tetanusTetanus antitoxoid antibody responseTraditionalInduction of immunity
Tobacco dependenceCigarette smokers Exhaled carbon monoxideTraditionalSmoking cessation 
Type 1 diabetes mellitus Patients with type 1 diabetes mellitusSerum hemoglobin A1C Traditional Glucose-lowering 
Type 1 Gaucher disease  Patients with Type 1 Gaucher diseaseSpleen volume, liver volume, hemoglobin and platelet count#TraditionalGlucosylceramide synthase inhibitor; Hydrolytic lysozomal glucocerebroside-specific enzyme
Type 2 diabetes mellitus Patients with type 2 diabetes mellitusSerum hemoglobin A1C Traditional Glucose-lowering 
X-linked hypophosphatemia Patients with X-linked hypophosphatemia Serum phosphateTraditionalFibroblast growth factor 23 inhibitor
Yellow fever  vaccinePatients at risk of exposure to yellow fever Neutralizing antibody responseTraditionalInduction of immunity

Pediatric Surrogate Endpoint Table

Disease or Use Patient Population Surrogate endpoint Type of approval appropriate forDrug mechanism of actionAge range 
Acetylglutamate Synthase deficiencyPatients with hyperammonemia due to N-acetylglutamate synthase deficiencyPlasma ammonia TraditionalCarbamoyl Phosphate Synthetase 1 activatorFrom birth to less than 18 years of age
Acromegaly Patients with acromegaly who don't respond to or cannot undergo other standard therapiesSerum Insulin-like growth factor-I (IGF-1) TraditionalGrowth hormone receptor antagonist2 years to less than 18 years
Acute bronchospasmPatients with acute bronchospasm associated with reversible obstructive airway disease or exerciseForced expiratory volume in 1 second (FEV1)Traditional Beta-2 adrenergic agonist5 years and older
AsthmaPatients with asthmaForced expiratory volume in 1 second (FEV1)Traditional Corticosteroid; Beta-2 adrenergic agonist; Anticholinergic4 years and older
Benign hematologyPatients with thrombocytopenia due to immune (idiopathic) thrombocytopenia or chronic hepatitis CPlatelet countTraditionalThrombopoietin receptor agonist1 year and older
Benign hematologyPatients with chronic iron overload or non-transfusion-dependent thalassemia syndromesSerum ferritin and liver iron concentrationAccelerated/Traditional§ Iron chelator2 years or older for chronic iron overload and 10 years older for Non-transfusion-dependent thalassemia syndromes
Benign hematologyPatients with severe aplastic anemiaHematologic response TraditionalThrombopoietin receptor agonist1 year and older
Benign hematologyPatients with venous thromboembolism (VTE)/pulmonary embolismTotal VTE and all-cause death TraditionalAnticoagulationAll pediatric age groups
Cancer: hematological malignancies Patients with acute lymphoblastic leukemiaDurable objective overall response rate (ORR)Accelerated/Traditional§ Mechanism agnostic*1 to 21 years
Cancer: hematological malignancies Patients with acute lymphoblastic leukemiaEvent Free Survival (EFS)Accelerated/Traditional§ Mechanism agnostic* 1 to 21 years
Cancer: hematological malignancies Patients with chronic myeloid leukemiaMajor hematologic and cytogenic responseAccelerated/Traditional§ Mechanism agnostic*3 to 20 years 
Cancer: hematological malignancies Patients with Acute Lymphoblastic Leukemia Serum Asparaginase Traditional Asparagine-specific enzymeAll pediatric age groups
Cancer: solid tumorsPatients with tuberous sclerosis complex with subependymal giant cell astrocytoma Durable objective overall response rate (ORR)Accelerated Kinase inhibitor1 year and older 
Cancer: solid tumorsPatients with merkel cell carcinomaDurable objective overall response rate (ORR)AcceleratedProgrammed death ligand-1 (PD-L1) blocking antibody12 years and older
Cancer: solid tumorsPatients with metastatic melanomaDurable objective overall response rate (ORR)AcceleratedMechanism agnostic*12 years and older
Cancer: solid tumorsPatients with metastatic melanomaProgression Free Survival (PFS)AcceleratedMechanism agnostic*12 years and older
Chagas disease Patients with Chagas diseaseImmunoglobulin G antibody negative against the recombinant antigens of T. cruziAcceleratedAntimicrobial2 to 12 years
Cystic fibrosis Patients with cystic fibrosisForced expiratory volume in 1 second (FEV1)Traditional Cystic fibrosis transmembrane conductance regulator potentiator2 years and older
CystinuriaPatients with cystinuriaUrinary cystineTraditionalReducing and complexing thiol9 years and older
Cytomegalovirus (CMV) CMV seropositive and hemotopoietic transplant recipients requiring prophylaxis  Plasma CMV-DNA exceeding threshold for starting treatment
 
TraditionalAntiviral12 years and older
Diphtheria vaccinePatients to be immunized against diphtheriaDiphtheria antitoxoid antibody TraditionalNeutralizing antibody6 weeks and older
Duchenne muscular dystrophy (DMD)Patients with DMD who have a confirmed mutation of the DMD gene that is amenable to exon 51 skippingSkeletal muscle dystrophinAcceleratedAntisense oligonucleotideMean age 8.9 years
Exocrine pancreatic insufficiencyPatients with exocrine pancreatic insufficiency due to cystic fibrosisFecal coefficient of fat absorption TraditionalReducing and complexing thiol6 months and older 
First aid antiseptic; Health care antiseptic; Consumer antisepticGeneral public, consumers, and health care professionalsBacterial count Traditional and Monograph  
Antimicrobial 
All pediatric age groups
Hepatitis A (Hep A) vaccinePatients to be immunized against Hep A Anti-Hep A virus antibody concentrationTraditionalInactivated hepatitis A virus vaccine Antiviral6 months and older
Hepatitis B (Hep B) vaccinePatients to be immunized against Hep B Anti-Hep B virus antibody concentrationTraditionalInactivated hepatitis B virus vaccine AntiviralAll pediatric age groups
Hepatitis B Virus (HBV)Patients with HBVSerum HBV DNATraditional Antiviral2 years and older
Hepatitis C Virus (HCV)Patients with HCV with or without cirrhosisSustained viral response (HCV-RNA) Traditional Antiviral5 years and older
Homozygous sitosterolemia (phytosterolemia)Patients with homozygous sitosterolemia (phytosterolemia)Plasma sitosterol and campesterol TraditionalDietary cholesterol absorption inhibitor 
Human Immunodeficiency Virus-1 (HIV-1)Patients with HIV-1 Undetectable plasma HIV-RNATraditionalAntiviral 4 weeks and older
Human Immunodeficiency Virus-1 (HIV-1)Highly treatment experienced HIV-1 patients Greater than 0.5 log reduction in plasma HIV RNATraditionalAntiviral Infected patients since birth
HypercholesterolemiaPatients with heterozygous familial hypercholesterolemiaSerum LDL-C TraditionalLipid-lowering 
Hypercholesterolemia Patients with homozygous familial hypercholesterolemiaSerum LDL-C TraditionalLipid-lowering  
HyperphosphatemiaPatients chronic or end stage kidney disease on dialysis with hyperphosphatemiaSerum phosphate TraditionalPhosphate binder 6 years and older 
Hypertension Patients with hypertension Blood pressureTraditionalAngiotensin II receptor blocker; Aldosterone antagonist1 to less than 17 years
Hypertension Patients with hypertension Mean arterial pressureTraditionalVasodilator Less than 17 years
HypothyroidismPatients with hypothyroidismThyroid-stimulating hormone (TSH)Traditional Thyroid hormone analog 
Influenza vaccinePatients to be immunized against influenza Hemagglutination inhibition antibody responseAcceleratedInactivated influenza virus vaccine 6 months and older
Japanese encephalitis vaccinePatients to be immunized against Japanese encephalitis Neutralizing antibody responseTraditionalInactivated Japanese encephalitis virus vaccine2 months and older
LipodystrophyPatients with congenital or acquired generalized lipodystrophySerum hemoglobin A1C , fasting glucose and triglycerides Traditional Leptin analog 
Melanoma Patients with advanced melanoma Durable Response Rate Traditional Mechanism unknown 
Meningococcal A C Y W-135 vaccinePatients to be immunized against meningococcal meningitis  Serum bactericidal antibody responseTraditionalInactivated influenza virus vaccine2 months and older
Meningococcal B vaccinePatients to be immunized against meningococcal meningitisSerum bactericidal antibody responseTraditionalInactivated meningococcal vaccine10 to 25 years
Nephropathic cystinosisPatients with nephropathic cystinosisWhite blood cell cystine and serum creatinine#TraditionalCystine depleting agent6 years and older
Phenylketonuria Patients with hyperphenylalaninemia due to tetrahydrobiopterin-responsive phenylketonuriaPlasma phenylalanine TraditionalPhenylalanine hydroxylase activator 1 month to 16 years
Polio vaccine Patients to be immunized against polioNeutralizing antibody responseTraditionalInactivated poliovirus vaccine6 weeks and older
Precocious pubertyPatients with central precocious pubertySerum luteinizing hormone TraditionalGonadotropin releasing hormone (GnRH) agonist 
Pulmonary Tuberculosis (TB) Patients with latent pulmonary TB Time to sputum culture conversion to negativeAcceleratedAntimicrobial 12 years and older
Rabies immune globulinPatients with suspected exposure to a rabid animalRabies neutralizing activity and antibody TraditionalInactivated rabies virus vaccine 
Secondary hyperparathyroidism Patients with secondary hyperparathyroidism associated with chronic kidney disease Serum intact parathyroid hormone (iPTH)  TraditionalVitamin D analog 
Tetanus vaccinePatients to be immunized against tetanusTetanus antitoxoid antibody TraditionalNeutralizing antibody6 weeks and older
Type 1 diabetes mellitus Patients with type 1 diabetes mellitusSerum hemoglobin A1CTraditional Glucose-lowering6 to 15 years
Type 1 Gaucher disease  Patients with type 1 Gaucher diseaseSpleen volume, liver volume, hemoglobin and platelet count#TraditionalHydrolytic lysozomal glucocerebroside-specific enzyme4 to 17 years 
Type 2 diabetes mellitus Patients with type 2 diabetes mellitusSerum hemoglobin A1CTraditional Glucose-lowering10 to 16 years
X-linked hypophosphatemia Patients with X-linked hypophosphatemia Serum phosphateTraditionalFibroblast growth factor 23 inhibitor1 year and older 
Yellow fever vaccinePatients at risk of exposure to yellow fever Neutralizing antibody responseTraditionalAttenuated yellow fever virus vaccine9 months and older

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