Stem cells: Information environment
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Transcript of Stem cells: Information environment
ARETE-ZOE, LLC 1334 E Chandler Blvd 5A-19, Phoenix 85048, Arizona, USA
STEM CELL REGISTRY
Alternative way of generating data from stem cell interventions performed under 21 CFR part 1271 (CGTP)
Problem statement Stem cells have characteristics that distinguish them from drugs, biologics, or medical devices. Considerable body of science has not yet been accumulated to develop and deliver safe and effective treatments. Their regulation remains unclear.
Advertising strategies
Patient autonomy
Regulatory uncertainty
Generating evidence
Information environment
NAP: Stem cell therapies (Nov 2014)
Improved information environment is essential for sound decision-making by all stakeholders
Marketing claims
by clinics offering stem cell therapies are not necessarily
supported by clinical evidence in
the scientific literature
Unproven stem cell
treatments can harm patients
by leading to complications
such as tumors, meningitis, or
even death
Patients who have
no other treatment
options
may be willing to take these risks if
there is a slight chance of success. �
Objective outcome measures
needed for assessment of the
effectiveness of stem cell therapies
Knowns and unknowns
Issues relating to truthfulness of commercial speech are not unique to stem cells
Corporate freedom of speech
Stakeholders
Patients
Physicians (regular healthcare providers)
Manufacturers of HCP/Ts, clinics
Producers of mass produced treatments
Regulators
Insurers, payers
Investors
Information Reliable
Accurate Timely
Safety Efficacy
Cost-effectiveness ROI
Regulations
In the U.S. International
Section 505
of the FD&C Act
DRUGS
Section 351 of the PHS Act
BIOLOGICS
Device provisions of the FD&C Act
DEVICE
Section 361 of the PHS Act only
Minimally manipulated
Regulations vary widely
Enforcement inconsistent
Offshore clinics
Medical tourism
Patient demand-driven
21 CFR part 1271
Minimal manipulation (1) For structural tissue,
processing that does not alter the original relevant characteristics of the tissue relating to the tissue's utility for reconstruction, repair, or replacement
(2) For cells or nonstructural tissues, processing that does not alter the relevant biological characteristics of cells or tissues.
ENVIRONMENT FACILITIES
EQUIPMENT SUPPLIES
REAGENTS
PROCESS RECOVERY
LABELLING STORAGE
DONORS DISTRIBUTION
HCT/Ps under section 361 of the PHS Act and 21 CFR part 1270 Manufactures of HCT/Ps that are: • Drugs • Medical Devices • Biological Products • Hematopoietic stem cells from
peripheral and cord blood • Reproductive cells and tissues • Human heart valves • Human dura mater
Ethical considerations
The Helsinki Declaration
In the treatment of an individual patient, where proven interventions do not exist or other known interventions have been ineffective, the physician, after seeking expert advice, with informed consent from the patient or a legally authorized representative, may use an unproven intervention if in the physician's judgement it offers hope of saving life, re-establishing health or alleviating suffering. This intervention should subsequently be made the object of research, designed to evaluate its safety and efficacy. In all cases, new information must be recorded and, where appropriate, made publicly available.
(The Helsinki Declaration, Article 37)
Information environment
How a patient will search for medical
information?
What a biomedical researcher can find in public domain?
Information as paid service: professional
specialized databases
Sharyl Attkisson TED Talks on Astroturf How patients search for medical information online
Information in public domain
Clinical Trial Registries
Biomedical Literature
Professional Societies
Information as paid service
Industry Insurers Healthcare providers Professional societies Academic research
Systematic review of available information in specialized databases Resource intensive, expensive, mandatory / driven by business need
Articles reports datasets
All stem cell trials ClinicalTrials.gov March 22, 2016
Autologous stem cell trials ClinicalTrials.gov March 22, 2016
0
500
1000
1500
2000
2500
Conditions studied
ClinicalTrials.gov August, 2015
805 1 12
1730
81
249
7 2
1858
43 373
137 Active, not recruiting
Approved for marketing
Available
Recruiting
Enrolling by invitation
Not yet recruiting
No longer available
Temporarily not available
Completed
Suspended
All SC trials: recruitment
ClinicalTrials.gov January 7, 2016
All SC trials: enrollment ClinicalTrials.gov January 7, 2016
0100200300400500600700800
All SC trials: Type of trial ClinicalTrials.gov January 7, 2016
4680
596
22
Interventional
Observational
Expanded access
All SC trials: funding
ClinicalTrials.gov January 7, 2016
2907
836
588
528 356
OtherNIH & OtherIndustryIndustry & OtherNIHIndustry & Other & NIHOther & U.S. FedIndustry & NIHU.S. FedIndustry & U.S. FedOther & NIH & U.S. FedU.S. Fed & NIH
All SC trials: sponsors ClinicalTrials.gov August, 2015
“Other” means: Trials Fred Hutchinson Cancer Research Center 192 National Cancer Institute (NCI) 177 M.D. Anderson Cancer Center 148 Memorial Sloan Kettering Cancer Center 100 National Heart, Lung, and Blood Institute (NHLBI) 91 Masonic Cancer Center, University of Minnesota 80 City of Hope Medical Center 72 Children's Oncology Group|National Cancer Institute (NCI) 59 St. Jude Children's Research Hospital 57 Baylor College of Medicine 53 Mayo Clinic 51
All SC trials: phases ClinicalTrials.gov January 7, 2016
0200400600800
10001200140016001800
0 1 1 & 2 2 2 & 3 3 4 notstated
402; 8%
4896; 92%
Has results
No results available
All SC trials: results
ClinicalTrials.gov January 7, 2016
Scientific publications
PubMed CT Registries vs. publications
> 250,000 hits “stem cells”
>4,200 human clinical trials
~140,000 animal studies
Publication bias
Multiple publication bias
Link between publications and CT#
Non-human experience
Multiple publication bias: ALS
0
1
2
3
4
5
6
7
8Additional publicationsidentified by NIH
Publications provided
Current situation
Patient demand Offered unproven therapies
Untreatable conditions
Alternative to invasive treatments
QoL (orthopedic injuries)
Cosmetic procedures
Medical tourism
Cutting edge innovation
Innovative surgery
But also widespread fraud
Difficult to distinguish
Outside FDA jurisdiction to limit risk to business
The Letter outlines three major areas of problems:
(1) the adipose stem cell product (stromal vascular fraction or SVF) is an unapproved biological drug
(2) non-homologous use of the product
(3) more than a dozen specific problems related to the production of the stem cell product SVF
Change in approach
Request for comments
Draft Guidances Relating to the Regulation of Human Cells, Tissues, or Cellular or Tissue-Based Products
Regulations.gov
Response
600 registered attendees
100 speaker requests
Hearing delayed
“The agency intends to schedule a scientific workshop to gather information from manufacturers of cell based products, clinical researchers, and other stakeholders regarding the generation of scientific evidence to facilitate the development of safe and effective cell
based therapeutics.”
Information gap: solution
Unproven to proven therapies Comparison to defined standard
Wide variety of approaches
SC types
Harvest site
SC Manipulation
SC Reintroduction
Imaging technologies
Follow-up, rehabilitation
Current standard of care
Datasets from insurers
Big data approach
Patient >> data
Patient vs. statistical pool
Technical requirements
Patient anonymity
Indication intervention outcome follow-up
Long-term follow-up & update from clinics
IPR protection
QoL studies, safety and efficacy, cost-effectiveness
Comparison against outcomes on defined standard of care as obtained from insurers
Technical requirements
Comparison against current standard of care
Continuous evaluation of coming data Safety and efficacy, QoL
Benefit-risk assessments
Cost-effectiveness compared to other options
Multiple different PME, and likely evolving
Learning ecosystem
Near real time analytical output
Questions?