Patients Matter and Patient Engagement

Patient Engagement

Individual patient

  • experience diseases and therapies differently
  • has unique perspective about treatments or diagnostic procedures

Opportunities for patients and caregivers to get involved with FDA

  • Evolution of Patient Engagement at FDA
  • Patient Engagement Collaborative
  • FDA and European Medicines Agency Patient Engagement Cluster
  • FDA Patient Council
  • MOU with the National Organization of Rare Disorders
  • FDA Patient Representative Program
  • Food and Drug Administration Safety and Innovation Act (FDASIA) Section 1137
  • Patient Reported Outcomes
  • Patient Focused Drug Development Initiative
  • Device Patient Preference Initiative
  • Devices Patient Engagement Advisory Committee
  • Additional Patient Resources


Video credit: FDA

Market Authorizations: VITRAKVI for NTRK cancer, FIRDAPSE for rare disease, XOSPATA for AML, reSET-O App, TRUXIMA rituximab biosimilar


Vitrakvi (larotrectinib) capsules and oral solution

 Loxo Oncology

INDICATION: Treatment of adult and pediatric patients with solid tumors that:

  • have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation
  • are metastatic or where surgical resection is likely to result in severe morbidity
  • have no satisfactory alternative treatments or that have progressed following treatment


  • Treatment based on a common biomarker across different types of tumors rather than location of tumor
  • Treatment for cancers based on tumor genetics rather than site of origin
  • New paradigm in the development of cancer drugs that are “tissue agnostic”

MECHANISM OF ACTION: Inhibitor of the tropomyosin receptor kinases (TRK), TRKA, TRKB, TRKC; TRK fusion proteins can act as oncogenic driver, promoting cell proliferation and survival in tumor cell lines


  • Three multicenter, open-label, single-arm clinical trials, n= 55 pediatric and adult patients with solid tumors with NTRK gene fusion with no satisfactory alternative treatments
  • Responding tumor types: Soft tissue sarcoma, salivary gland cancer, infantile fibrosarcoma, thyroid cancer and lung cancer
  • Overall response rate across different types of solid tumors: 75%
  • Response duration: 73% lasting at least six months, 39% lasting a year or more


  • Common side effects: Fatigue, nausea, cough, constipation, diarrhea, dizziness, vomiting, increased AST and ALT enzyme blood levels in the liver
  • May cause harm to a developing fetus or newborn baby


  • Accelerated approval based on specific genetic feature (biomarker); continued approval contingent upon verification and description of clinical benefit in confirmatory trials
  • Accelerated approval requirement: Verify and describe clinical benefit in adult and pediatric patients
  •  Priority Review, Breakthrough Therapy designation, Orphan Drug designation
  • Rare pediatric disease priority review voucher  denied



FIRDAPSE (amifampridine) tablets

 Catalyst Pharmaceuticals

INDICATION: Treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults


  • First treatment for LEMS
  • Rare autoimmune disorder affecting connection between nerves and muscles
  • Causes weakness and other symptoms in affected patients

MECHANISM OF ACTION: Not fully elucidated; broad spectrum potassium channel blocker.


  • Two clinical trials, n=64 adult patients, Firdapse vs. placebo
  • Endpoint: Quantitative Myasthenia Gravis score (a 13-item physician-rated categorical scale assessing muscle weakness) and Subject Global Impression (a seven-point scale on which patients rated their overall impression of the effects of the study treatment on their physical well-being)
  • Patients receiving Firdapse experienced a greater benefit vs. placebo


  • Most common side effects: Burning or prickling sensation (paresthesia), upper respiratory tract infection, abdominal pain, nausea, diarrhea, headache, elevated liver enzymes, back pain, hypertension and muscle spasms
  • Seizures and  hypersensitivity reactions such as rash, hives, itching, fever, swelling or trouble breathing


  • Priority Review, Breakthrough Therapy designations, Orphan Drug designation



XOSPATA (gilteritinib) tablets


INDICATION: Treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test


  • ~ 25-30% AML patients have FLT3 gene mutation; associated with aggressive form of disease and higher risk of relapse
  • First drug to be used alone in treating patients with AML having FLT3 mutation

MECHANISM OF ACTION: Inhibits multiple receptor tyrosine kinases, including FLT3


  •  Clinical trial, n=138 patients with relapsed or refractory AML with confirmed FLT3 mutation
  • Complete remission (no evidence of disease and full recovery of blood counts) or complete remission with partial hematologic recovery (no evidence of disease and partial recovery of blood counts) : 21%
  • Of the 106 patients requiring RBC or platelet transfusions; 31% transfusion-free for at least 56 days


  • Common side effects: Muscle and joint pain (myalgia/arthralgia), fatigue and elevated liver enzymes (liver transaminase)
  • Required monitoring for posterior reversible encephalopathy syndrome, prolonged QT interval, pancreatitis (inflammation in the pancreas)
  • May cause harm to a developing fetus or newborn baby.


  •  Fast Track, Priority Review designation, Orphan Drug designation
  • Postmarketing requirements: Clinical assessment of long-term safety and risks or rare adverse events (differentiation symdrome)



reSET-O App

Pear Therapeutics

INDICATION FOR USE:  Prescription cognitive behavioral therapy intended to be used in addition to outpatient treatment under the care of a health care professional, in conjunction with treatment that includes buprenorphine and contingency management


  • As part of FDA efforts to address the misuse and abuse of opioids
  • New tool to help more people with opioid use disorder successfully treat their addiction


  • App can be downloaded directly to a patient’s mobile device
  • Used while participating in an outpatient Opioid Use Disorder (OUD) treatment program
  • For training, monitoring and reminder tool for health care providers and patients
  • Compliance reward system– such as earning special icons on a prize wheel


  •  Multi-site, unblinded, controlled 12-week clinical trial, n=170 patients, with or without reSET-O
  • Supervised administration of buprenorphine and urine screens; contingency management system to reward negative urine tests
  • Illicit drug use, abstinence improvement : No decrease  with reSET-O vs. buprenorphine treatment and contingency management alone
  • Retention in treatment program for 12 weeks: 82.4%  with reSET-O vs. 68.4% without reSET-O
  • Adverse events: Typical of patients with OUD – cardiovascular disease, gastrointestinal diseases, HIV, Hepatitis C, nutritional diseases, risk of overdose, depression, mania, suicidal behavior and suicidal ideation and attempts


  • Predicate device, reSET App- classified via De Novo pathway in 2017
  • Regulation Number : 882.5801
  • Classification : II
  • Classification Name: Computerized Behavioral Therapy Device For Psychiatric Disorder
  • Product Code: PWE



Truxima (rituximab-abbs)

Celltrion Inc.

INDICATION: Non–Hodgkin’s Lymphoma (NHL). Treatment of adult patients with:

  • Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
  • Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy
  • Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy


  • First biosimilar to Rituxan (rituximab, Genentech Inc.)  
  • Approval based on a review of extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, other clinical data
  • Demonstrated that Truxima is biosimilar to Rituxan
  • Not as an interchangeable product.


Image credit: Loxo, Catalyst, Astellas, Pear, Celltrion










News & Views: Duodenoscope concerns, Biomarker qualification framework, Device classification procedures, Data integrity, NASH guidance, Non-device software report, To eat or not to eat?


Interim Results of Duodenoscope Reprocessing Studies Conducted in Real-World Settings: FDA Safety Communication

FDA ordered all U.S. duodenoscope manufacturers (Olympus, Fujifilm, Pentax) to conduct 2 postmarket surveillance studies on whether health care facilities were able to properly clean and disinfect devices

  • Study to sample and culture reprocessed duodenoscopes
  • Study to nassess how effectively the trained hospital staff follow the manufacturer reprocessing instructions (human factors)
  • At least 10% of the samples have been collected assuming <0.4% contamination rate

Interim results indicate higher-than-expected contamination rates after reprocessing

  • Up to 3% samples testing positive for enough low concern organisms
  • Up to 3% of samples testing positive for high concern organisms- E. coli,  Pseudomonas aeruginosa
  • Root cause analyses are underway;  final results in 2019

Safety communication to hospitals and health care providers

  • Following the manufacturer’s reprocessing and maintenance instructions not sufficient to avoid all infections
  • FDA been working with developers on new product designs, including disposable components



Biomarker Qualification: Evidentiary Framework

Evidentiary framework to support biomarker qualification with recommended components

  • Type and level of evidence
  • Broadly applicable regardless of the type of biomarker or context of use (COU)
  • Qualified biomarker can be used across multiple drug development programs

Framework consists of 

  • Drug development need
  • Defining the COU
  • Potential benefits if the biomarker is qualified for use
  • Potential risks of biomarker in drug development program

Biomarker validation




Medical Device Classification Procedures: Incorporating Food and Drug Administration Safety and Innovation Act Procedures


  • Medical device classification procedures for certain devices and requiring premarket approval applications for preamendments to Class III devices by using administrative orders, rather than rulemaking
  • Do not affect the classifications of previously cleared or approved devices

Principle benefits

  • Reduction in regulatory and economic burden and decreased timelines by eliminating paperwork filing requirements
  • Enhanced consistency and uniformity across reclassification proceedings
  • Cost and time savings will accrue to both medical device manufacturers and to Agency.



Data Integrity and Compliance With Drug CGMP

Clarify role of data integrity in current good manufacturing practice (CGMP) for drugs

  • All data expected to be reliable and accurate
  • Flexible and risk-based strategies to prevent and detect data integrity issues
  • Consider design, operation, monitoring based on risk to patient, process, product
  • Management’s involvement essential in preventing and correcting conditions that lead to data integrity problems.
  • Create a quality culture with data integrity as core value

Q & As on broad range of topics provided



Noncirrhotic Nonalcoholic Steatohepatitis With Liver Fibrosis: Developing Drugs for Treatment Guidance for Industry

Guidance for clinical development of drugs for treatment of noncirrhotic nonalcoholic steatohepatitis (NASH) with liver fibrosis

  • Necessary components of drug development program


  • General Considerations
  • Phase 2 Development Considerations: Early and Late trials
  • Phase 3 Development Considerations: Inclusion / Exclusion criteria,  trial design and efficacy endpoints, safety considerations, pediatric considerations

NASH guidance


Report on Non-Device Software Functions 

Certain software functions excluded from definition of device under section 201(h) FD&C Act (21 U.S.C. 321(h))

  • Administrative support of a health care facility
  • Maintaining or encouraging a healthy lifestyle and unrelated to the diagnosis, cure, mitigation, prevention, or treatment of disease or condition
  • Serving as electronic patient records; not intended to interpret or analyze
  • Transferring, storing, converting formats, displaying data
  • Certain types of clinical decision support to a health care provider unless interpreting or analyzing

Report based on information from: DHHS offices, representatives of patients, consumers, health care providers, startup companies, health plans or other third-party payers, venture capital investors, information technology

Analysis based on: Impact to patient safety, Benefits and risks to health, Best practices to promote safety, education, and competency

Findings: More benefits than risks to patient safety and health related to these software functions

Details best practices: Implementation, training techniques, and use, which could promote safety, education, and competency related to these software functions


Image credit: FDA


FDA News & Views: Real-World Evidence framework, Women’s Health Research roadmap, Clinical Testing advances, Human Genetic Variant databases, De Novo pathway improvement, Collaborative Community toolkit, Opioid Use Disorder challenge, Blood Glucose Monitors safety/accuracy, Patient Engagement Advisory Committee


Framework for Real-World Evidence Program

Framework for evaluating potential use of real-world evidence (RWE) to help support the approval of a new indication for a drug
  • Already approved under section 505(c) of the FD&C Act
  • Adding or modifying indication, adding new population, adding comparative effectiveness or safety information
  • Help satisfy postapproval study requirements
  • Does not apply to medical devices

Three-part approach for assessing  use of real world data (RWD) to generate RWE

  •  Are the RWD fit for use?
  • Can study design used to generate RWE provide adequate relevant scientific evidence?
  • Does study conducted meet FDA regulatory requirements for study monitoring and data collection?

Women’s Health Research Roadmap

FDA Office of Women’s Health (OWH) research priority areas to advance the science of women’s health

  1. Advance Safety and Efficacy of FDA-regulated products used by women
  2. Improve Clinical Study Design and Analyses to better identify and evaluate possible sex differences
  3. Novel Modeling and Simulation Approaches  to aid in regulatory evaluation
  4. Advances in Biomarker Science to identify, evaluate, qualify clinical and non-clinical biomarkers and surrogate endpoints
  5. Expand Data Sources and Analysis  to identify, develop, evaluate data sources to assess postmarket toxicity or safety and effectiveness
  6. Improve Health Communications to develop, evaluate, use tools to make informed health-related decisions
  7. Emerging Technologies for identification of sex differences to use of emerging technologies



New Steps to Advance Clinical Testing to Deliver New Cures



FDA Recognition of Public Human Genetic Variant Databases

Genetic variant database collect, organize, publicly document evidence supporting links between human genetic variant and disease

  • Better understanding relationships between genotypes and diseases can aid in the diagnosis and treatment of individuals with genetic conditions
  •  Mechanism for test developers to leverage publicly accessible databases to support  regulatory review of genetic and genomic tests

Clinical Genome Resource (ClinGen) consortium’s ClinGen Expert Curated Human Genetic Data is first FDA-recognized publicly-available genetic variants database




Improvements to the De Novo pathway for novel medical devices to advance safe, effective, and innovative treatments for patients

Establish procedures and criteria for medical device De Novo classification process

  • For new medical devices with no legally marketed predicates
  • Vehicle for establishing new predicates reflecting modern standards for performance and safety
  • Make pathway significantly more efficient and transparent
  • Expecting more use of pathway for new devices

De Novo request granted

  • new device is legally marketed and in compliance with regulatory controls
  • new classification regulation established
  • new device serves as predicate device for 510(k) submissions of same type devices
  • Federal Register notification of new classification regulation, new special controls
  • posting of granting order and decision summary.

De Novo request decline

  • general/special controls  insufficient to provide reasonable assurance of safety and effectiveness
  • data insufficient to determine whether controls can provide reasonable assurance of safety and effectiveness of the device
  • probable benefits do not outweigh probable risks
  • device remains in class III and may not be legally marketed



Collaborative Community Toolkit

Collaborative community is continuing forum with private- and public-sector members, including FDA, work together on medical device challenges

  • Challenges ill-defined or no consensus
  • Challenges and outcomes are complex
  • Partners are interrelated
  • Incremental or unilateral efforts to address challenge have been ineffective
  • Partners seek to optimize efforts, including preventing duplication of efforts
  • Better outcomes with integrating different perspectives, experiences, resources, expertise



Selections for FDA Innovation Challenge for Devices to Prevent and Treat Opioid Use Disorder

Over 250 applications received for Opioid Use Disorder (OUD) challenge; selections include

  • prediction of risk of OUD
  • detection of  opioid overdose
  • dispensing medication
  • providing pain treatment alternatives to opioids

Selected applicants receive Breakthrough Device designation



Steps to advance safety and accuracy of blood glucose monitors

Two revised draft guidances regarding blood glucose monitors used in health care and home settings

  • Based stakeholder feedback requesting more clarification on design considerations and recommended standards
  • To improve development of new blood glucose meters based on feedback from both patients and health care providers especially on usability of glucose monitors

Blood Glucose Monitoring Test Systems for Prescription Point-of-Care Use

Self-Monitoring Blood Glucose Test Systems for Over-the-Counter Use



Patient Engagement Advisory Committee (PEAC)

PEAC held on Nov 15, 2018, to discuss topic “Connected and Empowered Patients: e-Platforms Potentially Expanding the Definition of Scientific Evidence”

  • Leveraging  patient-generated health data, such as social media, sensors, patient-driven registries, to better engage patients
  • Social media and other web platform  for virtual patient communities
  • Resource for postmarket study design, performing surveillance for adverse events, issuing recalls, communicating signals to public

FDA needs to take following steps 

  • Standardize how data is collected, used and applied
  • Ensure language communicated to patients be clear and understandable
  • Ensure data collected is de-identified
  • Ensure a high level of integrity with the data collected


Image credits: FDA