Embed Size (px)
Citation preview
Biomedical Engineering, Biostatistics and Epidemiology at Stellenbosch University
Prof Martin Nieuwoudt
DST/NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA)
and Biomedical Engineering, Dept of Mechanical and
Mechatronic Engineering, Stellenbosch University
Presentation plan Part 1: Definition + Scope: Bioengineering/Biomedical Engineering & an example from experience Part 2: Definition + Scope: Biostatistics + Epidemiology. SACEMA & examples Part 3: ‘BERG’ - examples, and the future: IBE
???’s
Definition+ Scope: Bioengineering/Biomedical Engineering
Application of Biology - and Physics, Chemistry, Mathematics,
Computer Science
To solve real-world problems related to life sciences or its
applications
Using Engineering's Analytical and Synthetic Methodologies
“Any applications of Physics, Mathematics, Sciences and
Engineering at the intersections of Biology and/or Medicine,
aimed at solving or improving Health-related problems”
Part 1
Example of medical problem: Liver Failure 2 types: Acute (AHF) and Acute-on-Chronic Hepatic failure (AOCHF) Diffs are in speed: - AHF = days - AOCHF = acute loss of liver function following chronic disease leading to
multi-organ failure within 4-6 weeks, mortality rate ~ 50%
Treatment: - Gold standard AOCHF = Orthotopic Liver transplantation (OLT) BUT - Global shortage of donor organs - Extremely costly & not all succeed - Permanent immunosuppression after
An urgent need exists to either ‘bridge’ a patient while waiting for OLT, or to allow the innate liver to autonomously heal.
Intense research on extracorporeal liver support systems for decades
Blood returnto patient
Circulatingpump
Bio-reactorOxygenNutrients
CO2
Blood frompatient
Bio-artificial liver (BAL) technology
Basic principle
Progress in BALs has been hampered by: • Technical difficulty of research • Competition against gold-standard (OLT) • Expense
Developing a functional BAL requires: 1. 3D Cell culturing environment
• cell source/type, cell number/mass - cell isolation method • bioreactor oxygenation, functional evaluations
Need to build a Molecular Biology / Tissue Engineering lab (and manage it)
2. Systems modeling for • Flow dynamics/Design optimization • Pharmacokinetic efficacy
Need skills that come from Engineering
3. Clinical efficacy • Animal model/s • FDA approval • Stage I,II,III Human testing
Need skills that come from the Clinical world Result: Time consuming – The Science is very challenging, Multi-disciplinary interactions, which change in nature over time, Immensely costly
1. 3D Cell culturing environment
Steps: 1. Cell type? 2. Cell isolation 3. In vitro culturing
methods 4. In vitro efficacy/
functionality
2. Modeling
Possibilities: 1. Mass transfer 2. CFD – size and flow
optimization 3. Pharmacokinetic
compartmental models – in vivo efficacy
3. The Result: Model
3. The Result: Actual system - mk1
Control system
4. Pre-clinical efficacy: Animal trials
Issues: • Complex – Design + Personnel • Expensive • But enables crucial design
optimization
1. Technical/Scientific review
2. Commercialization Strategy review
Review Phase: - 7 years down the line
Country Application no. Status
RSA 2000/4861 (provisional patent
application) Superseded by PCT Patent Application PCT/IB 01/01549
PCT PCT/IB 01/01549 Superseded by national phase applications
FRANCE 0111857 PATENTED
ITALY MI2001A 001865 PATENTED
NETHERLANDS 1018942 PATENTED
SOUTH AFRICA 2003/1111 PATENTED
BRAZIL PI 0113876-6 Examination requested
CANADA 2,422,230 Examination requested
CHINA 01815608.8 PATENTED
EPO 01960998.1 Patent allowed. To be validated in individual countries by 30 March 2008
EURASIA 004455 PATENTED
JAPAN 2002/527014 Pending – Request for Examination due 27 August 2008
KOREA 10-2003-7003326 Notification of grant issued
USA 7,129,082 PATENTED
INDIA 530/CHENP/2003 Response to first Official Action filed
Examples of international BAL groups – 2+ years of negotiations
• ELAD (Vitagen)
hollow fiber cartridges, C3A immortalized human cells, charcoal toxin clearance column, phase III human trails not completed due to market/investor retreat
• HepatAssist (Circe/Arbios- Demetriou et al)
hollow fiber cartridges, porcine primary hepatocytes, 6 hour treatments, Phase II-III clinical trials halted
• AMC –BAL (Chamuleau et al)
hollow fiber cartridge with polyester mesh cell scaffolding, current Phase II human trials
Result…There is no bio-artificial device accepted in current clinical practice
Some lessons:
1. Initial project planning is critical to long term success
2. Need a multidisciplinary team with proper management
3. Understand your technology’s value proposition, i.e. ‘edge over the competition’
4. Understand the regulatory environment early on, e.g. FDA, CE, what your target markets are and what it will take to get a product into those markets
5. Validate your key assumptions with international experts in the field early on
6. Without protectable IP you cannot compete. High quality legal and IP support is crucial to ensuring proper legal agreements
- “verbal agreements aren’t worth the paper they aren’t written on”
7. Build a reputation in the relevant field through quality peer-reviewed publications and networking
Definition + Scope: Epidemiology From the Greek: “What ails the people” – Hippocrates
Patterns, Causes, and Effects of diseases in defined populations
Public health / policy-making - evidence-based practice Identify risk
factors for diseases and targets for preventive healthcare
Study design, Data Collection, Statistical analysis of data
Mathematical Modeling
Interpretation and Dissemination of results
Definition + Scope: Biostatistics Design of Bio/Medical experiments
Collection, Summarization, Analysis of resulting data
Interpretation/Inference of results
- Medical biostatistics exclusive to medicine and health
Part 2
CoE for the ‘quantitative modelling of the prevalence and management of disease’. 8 full-time staff, approx. 25 post graduate students Focus on major health issues in Africa: • Develop human capacity and infrastructure to advance epidemiological
modelling and analysis • Initial emphasis on research on epidemiology, control and management
of HIV/AIDS, TB, Malaria, • Later on, non-communicable diseases as additional staff and funding
become available • Provide firm scientific basis for health policy and planning locally and
internationally.
SACEMA - SA Centre of Excellence for Epidemiological Modelling and Analysis Inaugural statement:
SACEMA
Garden
STIAS – our neighbour (Stellb Inst for Advanced Studies)
What sort of people are we? People with strengths in: • Statistics – analysis and modelling • Data manipulation and interpretation • Mathematics –differential equations, linear algebra, probability. • Computer programming of mathematical problems. • Understanding of biological and medical issues. Why do we need mathematics to understand disease? - Data are often so complicated that we cannot interpret them except through models.
Example 1: Modelling short and long term Immune Response to HAART
Example 2: “Comparison of healthy paediatric lymphocyte subsets from South Africa to the US and Europe”
“Immunological reference intervals in healthy South African children” Until now paediatric reference intervals for blood markers in use in SA NHLS adopted from international publications
Changes in HIV prevalencein antenatal clinics in Harare1984-2007
Start of Year
1983 1986 1989 1992 1995 1998 2001 2004 2007
HIV
pre
va
len
ce
(%
)
4
8
12
16
20
24
28
32
36
Example 3: Determining HIV Prevalence in selected communities
Part 3
The SU Biomedical Engineering Research Group (BERG)
Well established and productive. Currently has 18 post graduate students. http://stbweb02.stb.sun.ac.za/berg/
We had our first Biomedical Engineering and Technology Conference In 2014. Very well attended. More than ½ the audience was international Planning another one in 2016
A few examples of recent post graduate projects: • Computational modeling of Biomechanics for total knee replacements • Development and testing of patient-specific knee joints • Development of a joint-type knee wear simulator • Custom-manufactured artificial intervertebral disc • Design of an impedance guided intra-arterial catheter • Needle positioning system for percutaneous procedures • Non-invasive artificial pulse oximetry • New orthodontic appliance using non-conventional electromechanical
methods • Magnetic intra-uterine manipulator • Fluid interaction simulation of a bioprosthetic valve for transcatheter aortic
valve implantation • Modeling and simulation of an aortic heart valve • Low cost slave manipulator for a minimally invasive robotic surgical system • Motion capture system for use in the optimization of road cycling
kinematics • Nystagmus and eye reflex sensor • Decision support system for telemedicine management • Analysis of EEG wave forms for brain-computer interfaces…………………phew!
The future: ‘Institute for Biomedical Engineering’ (IBE)
BERG has grown in capacity to the point where the time is right to transition it into an Institute. My task - to create the IBE (has high-level institutional approval within SU) Intended characteristics: • MSc, PhD, Meng, DEng co-degrees in Biomedical Engineering
with KULeuven and other Universities in the EU • Multi-Faculty + Dept’s • Entry of grad student from any discipline • Many local + international partnerships/collaborations • International staff and student exchange • IEEE registered chapter • Full-time staff
