NGS in Clinical Research: Meet the NGS Experts Series Part 1QIAGEN
Next generation sequencing has revolutionized clinical testing but has also created novel challenges. This presentation will give an overview of state of the art clinical NGS and discuss validation, clinical implementation as well as the migration from gene panels to exome sequencing for inherited disorders with clinical and genetic heterogeneity. In addition, important shortcomings such as difficulties with regions of high sequence homology will be discussed.
A micro-array is a tool for analyzing gene expression that consists of a small membrane or glass slide containing samples of many genes arranged in a regular pattern.
This was made by me while I was in Masters. I have made few animations. I hope it makes understanding better.
The content is made by searching through internet and referencing books. I do not claim any content in whole presentation except the animations made on the subject.
NGS in Clinical Research: Meet the NGS Experts Series Part 1QIAGEN
Next generation sequencing has revolutionized clinical testing but has also created novel challenges. This presentation will give an overview of state of the art clinical NGS and discuss validation, clinical implementation as well as the migration from gene panels to exome sequencing for inherited disorders with clinical and genetic heterogeneity. In addition, important shortcomings such as difficulties with regions of high sequence homology will be discussed.
A micro-array is a tool for analyzing gene expression that consists of a small membrane or glass slide containing samples of many genes arranged in a regular pattern.
This was made by me while I was in Masters. I have made few animations. I hope it makes understanding better.
The content is made by searching through internet and referencing books. I do not claim any content in whole presentation except the animations made on the subject.
Deciphering DNA sequences is essential for virtually all branches of biological research. With the
advent of capillary electrophoresis (CE)-based Sanger sequencing, scientists gained the ability to
elucidate genetic information from any given biological system. This technology has become widely
adopted in laboratories around the world, yet has always been hampered by inherent limitations in
throughput, scalability, speed, and resolution that often preclude scientists from obtaining the essential
information they need for their course of study. To overcome these barriers, an entirely new technology
was required—Next-Generation Sequencing (NGS), a fundamentally different approach to sequencing
that triggered numerous ground-breaking discoveries and ignited a revolution in genomic science.
Utilization of NGS to Identify Clinically-Relevant Mutations in cfDNA: Meet t...QIAGEN
Pancreatic cancer is a uniquely lethal malignancy characterized by frequent mutations in KRAS, CDKN2A, SMAD4, TP53 and many others. We have shown that KRAS mutation can be detected in cell-free, circulating tumor DNA (ctDNA) isolated from the plasma in a subset of patients and is associated with poor prognosis. The ability to simultaneously detect multiple pancreatic cancer-specific mutations in ctDNA would open a new avenue for detection of clinically-relevant mutations. In this study, we performed ultra-deep sequencing of ctDNA from advanced pancreatic cancer patients prior to treatment with Gemcitabine and Erlotinib following target enrichment. Somatic, non-synonymous variants were identified in 29 different genes at allele frequencies typically less than 0.5%. Updated results of ultra-deep NGS analysis will be presented.
Course: Bioinformatics for Biomedical Research (2014).
Session: 4.1- Introduction to RNA-seq and RNA-seq Data Analysis.
Statistics and Bioinformatisc Unit (UEB) & High Technology Unit (UAT) from Vall d'Hebron Research Institute (www.vhir.org), Barcelona.
Course: Bioinformatics for Biomedical Research (2014).
Session: 2.3- Introduction to NGS Variant Calling Analysis.
Statistics and Bioinformatisc Unit (UEB) & High Technology Unit (UAT) from Vall d'Hebron Research Institute (www.vhir.org), Barcelona.
AGRF in conjunction with EMBL Australia recently organised a workshop at Monash University Clayton. This workshop was targeted at beginners and biologists who are new to analysing Next-Gen Sequencing data. The workshop also aimed to provide users with a snapshot of bioinformatics and data analysis tips on how to begin to analyse project data. An introduction to RNA-seq data analysis was presented by AGRF Senior Bioinformatician Dr. Sonika Tyagi.
Presented: 1st August 2012
It contains information about- DNA Sequencing; History and Era sequencing; Next Generation Sequencing- Introduction, Workflow, Illumina/Solexa sequencing, Roche/454 sequencing, Ion Torrent sequencing, ABI-SOLiD sequencing; Comparison between NGS & Sangers and NGS Platforms; Advantages and Applications of NGS; Future Applications of NGS.
Personalised medicine holds great promised for both improving patients’ outcomes and enhancing the efficiency of treatment. Medicines paired with diagnostics are the backbone of personalised medicine, presenting new challenges in for health technology assessment. The situation in England, particularly how NICE might respond to this challenge, was the focus of the third networking event co-sponsored by the Association of the British Pharmaceutical Industry association (ABPI) and the British In Vitro Diagnostics Association. At this one-day event, speakers set the stage for discussion by presenting defining the context of this challenge for England.
OHE’s Adrian Towse presented on the economics. He discussed the elements of value of a diagnostics test (see our earlier blog post) and described the context necessary to produce useful assessments and to ensure subsequent use in the marketplace. His topics included issues of evidence generation, incentives for innovation, flexible approaches to access coincident with evidence development, and encouraging uptake and use.
Deciphering DNA sequences is essential for virtually all branches of biological research. With the
advent of capillary electrophoresis (CE)-based Sanger sequencing, scientists gained the ability to
elucidate genetic information from any given biological system. This technology has become widely
adopted in laboratories around the world, yet has always been hampered by inherent limitations in
throughput, scalability, speed, and resolution that often preclude scientists from obtaining the essential
information they need for their course of study. To overcome these barriers, an entirely new technology
was required—Next-Generation Sequencing (NGS), a fundamentally different approach to sequencing
that triggered numerous ground-breaking discoveries and ignited a revolution in genomic science.
Utilization of NGS to Identify Clinically-Relevant Mutations in cfDNA: Meet t...QIAGEN
Pancreatic cancer is a uniquely lethal malignancy characterized by frequent mutations in KRAS, CDKN2A, SMAD4, TP53 and many others. We have shown that KRAS mutation can be detected in cell-free, circulating tumor DNA (ctDNA) isolated from the plasma in a subset of patients and is associated with poor prognosis. The ability to simultaneously detect multiple pancreatic cancer-specific mutations in ctDNA would open a new avenue for detection of clinically-relevant mutations. In this study, we performed ultra-deep sequencing of ctDNA from advanced pancreatic cancer patients prior to treatment with Gemcitabine and Erlotinib following target enrichment. Somatic, non-synonymous variants were identified in 29 different genes at allele frequencies typically less than 0.5%. Updated results of ultra-deep NGS analysis will be presented.
Course: Bioinformatics for Biomedical Research (2014).
Session: 4.1- Introduction to RNA-seq and RNA-seq Data Analysis.
Statistics and Bioinformatisc Unit (UEB) & High Technology Unit (UAT) from Vall d'Hebron Research Institute (www.vhir.org), Barcelona.
Course: Bioinformatics for Biomedical Research (2014).
Session: 2.3- Introduction to NGS Variant Calling Analysis.
Statistics and Bioinformatisc Unit (UEB) & High Technology Unit (UAT) from Vall d'Hebron Research Institute (www.vhir.org), Barcelona.
AGRF in conjunction with EMBL Australia recently organised a workshop at Monash University Clayton. This workshop was targeted at beginners and biologists who are new to analysing Next-Gen Sequencing data. The workshop also aimed to provide users with a snapshot of bioinformatics and data analysis tips on how to begin to analyse project data. An introduction to RNA-seq data analysis was presented by AGRF Senior Bioinformatician Dr. Sonika Tyagi.
Presented: 1st August 2012
It contains information about- DNA Sequencing; History and Era sequencing; Next Generation Sequencing- Introduction, Workflow, Illumina/Solexa sequencing, Roche/454 sequencing, Ion Torrent sequencing, ABI-SOLiD sequencing; Comparison between NGS & Sangers and NGS Platforms; Advantages and Applications of NGS; Future Applications of NGS.
Personalised medicine holds great promised for both improving patients’ outcomes and enhancing the efficiency of treatment. Medicines paired with diagnostics are the backbone of personalised medicine, presenting new challenges in for health technology assessment. The situation in England, particularly how NICE might respond to this challenge, was the focus of the third networking event co-sponsored by the Association of the British Pharmaceutical Industry association (ABPI) and the British In Vitro Diagnostics Association. At this one-day event, speakers set the stage for discussion by presenting defining the context of this challenge for England.
OHE’s Adrian Towse presented on the economics. He discussed the elements of value of a diagnostics test (see our earlier blog post) and described the context necessary to produce useful assessments and to ensure subsequent use in the marketplace. His topics included issues of evidence generation, incentives for innovation, flexible approaches to access coincident with evidence development, and encouraging uptake and use.
Multidisciplinary Approach to Prostate Cancer and Changes in Treatment Decisi...CrimsonpublishersCancer
In order to demonstrate the impact of multi-disciplinary care in the community oncology setting, we evaluated treatment decisions following the initiation of a dedicated genitourinary multi-disciplinary clinic (GUMDC).
Cancer Clinical Trials_ USA Scenario and Study Designs.pdfProRelix Research
Clinical trials in oncology are vital for the advancement of cancer treatments and
care. The US is at the forefront of these clinical trials, with many different study
designs being used to assess the efficacy and safety of new treatments. This article
will explore the current state of oncology clinical trial services in the US, as well as
discuss different types of study designs that are commonly used. It will provide
insight into how these trials are conducted, what data is collected, and how this
information can be used to improve patient care.
The United States Food and Drug Administration (FDA) has released
several guidance documents over the years through the Oncology Center
of Excellence to support the development of oncologic treatments and
diagnoses. Furthermore, information on the clinical trials for the treatment
of different types of cancer or specific interventions can be found on the
National Cancer Institute (NCI) website and Clinical Trials. Currently,
ClinicalTrials.gov, a website maintained by the National Library of
Medicine (NLM) and the National Institutes of Health (NIH) contains
listings of publicly and privately sponsored trials and includes information
on 91,937 studies related to cancer indicating the high volume of
research being conducted in this field.According to the World Health Organization (WHO), cancer is the leading
cause of death worldwide, with a death rate of one in six in 2020 (1).
Aside from the high mortality rate and morbidity associated with cancer, it
also negatively impacts the quality of life and poses a significant financial
burden on patients and payers making it imperative to develop effective
treatments for the disease. According to Global Cancer Observatory
(GLOBACAN), the United States accounted for 13.3% of all estimated
new cases of cancer in 2020 (2). In 2020, the single leading type of
cancer in the United States was breast cancer (11.1%) followed by lung
cancer (10%), prostrate (9,2%), colorectum (6.8%), and melanoma of the
skin (4.2%). Despite the significant prevalence of cancer and numerous
clinical trials conducted for oncology treatments, data have shown an
almost 95% attrition rate for anticancer drugs from Phase I trials until
marketing authorization. Various factors such as inaccurate preclinical
models, lack of suitable biomarkers in clinical trials, and a disconnect
between industry, academia, and regulators are responsible for the high
attrition rate (3). Therefore, it is vital to develop suitable study designs
and protocols for candidate molecules such that they obtain regulatory
approval and can be marketed. In addition to these challenges, the
development of anti-cancer agents comes at a monumental cost of an
estimated $2.8 billion. Several factors such as the choice of relevant
endpoints, the choice of appropriate biomarkers that are guided by tumor
biology, and careful patient selection are expected to improve the overall
fate of oncologic agents in the clinical trial phase
The dream of any physician and consequently every patient is to receive the right treatment in the right time with cost effectiveness. To achieve this goal, the 3 pillars: evidence based medicine, clinical research innovation & resources utilization should be integrated efficiently.
In this presentation, I'll try to comprehensively review the following:
1- How are we used to perform clinical trials in Oncology?
2- Does it fits in today’s needs?
3- Integration of biology knowledge in shaping drug development
4- New Clinical trial designs “Can they offer solution for accelerating drug development?”
5- The supporting infrastructure role in clinical trial execution
How general internists can participate in the continuum of care for patients with cancer. (Talk given at Internal Medicine Grand Rounds, St. Elizabeth Hospital, General Santos City, 10 Feb 2021.)
By preventing confounding from other circumstances, a successful clinical trial reduces the heterogeneity of the assessment and offers an objective assessment of the intervention.
With the exception of the intervention that each group receives, randomization ensures that every patient has an identical likelihood of obtaining any of the therapies being studied.
On 31 October 2019, Adrian Towse and Chris Henshall from the Office of Health Economics (OHE) presented at the G20 meeting on antimicrobial drugs R&D in Paris organised by the Wellcome Trust. The topic of their presentation was HTA and payment mechanisms for new drugs to tackle antimicrobial resistance.
This presentation looks at ways in which governments can set prices, including “cost plus”, value, and the external referencing of prices elsewhere. It looks at the role that competition can play in keeping down prices. In that context it briefly discusses pricing proposals being considered in Malaysia. It makes the case for using HTA to inform pricing decisions.
Adrian Towse
% GDP spending in UK, G5 countries and OECD upper middle income countries. W...Office of Health Economics
This presentation looks at rates of GDP spend on health care, distinguishing between categories of country (i.e. levels of GDP pre capita). It looks at the relationship between rates of spending and moves to universal health coverage, and explores alternative ways of increasing expenditure and making decisions about which services to provide with the money available.
The role of real world data and evidence in building a sustainable & efficien...Office of Health Economics
This presentation defines RWD and RWE in the context of digital health, and looks at potential uses for RWD and RWE. It briefly sets out the current landscape in Malaysia and looks at the challenges in using RWE. In particular, the issues of access, governance and ensuring good quality are considered.
The aim of this educational symposium was to discuss why we should seek value across the health care system and how we can apply existing research methods to measure the value of services. While considerable political attention in developed countries continues to be focused on drug spending, there is also growing awareness of the significant contribution of non-drug components of health care (e.g., hospital services and inefficient care delivery) to overall spending growth and patient affordability. At the same time, there is growing interest in making greater use of value assessment and value-based payment to control spending and better align it with care quality. In order to promote greater value, and to do so in ways that respond to the needs of payers and patients, it is essential to assess value across both drug- and non-drug interventions and health care services. This panel will offer expert viewpoints to identify and discuss gaps in value information, rationale and approaches to track and reduce system-wide low value care, and research methods for how to measure health care services.
Role Substitution, Skill Mix, and Provider Efficiency and Effectiveness : Les...Office of Health Economics
Graham participated in an organised session on Monday July 15th 2019. In the session he presented his paper with his co-author Ioannis Laliotis from the London School of Economics. The paper revisits the relationship between workforce and maternity outcomes in the English NHS in an attempt to contribute knowledge to an important policy question for which there has been a paucity of research.
This research explores the feasibility of introducing an Outcome-Based Payment approach for new cancer drugs in England. A literature review explored the current funding landscape in England, the available evidence on existing OBP schemes internationally, and
which outcomes cancer patients value most. Two focus groups and an online survey with patients and carers, as well as interviews with NHS and government stakeholders, healthcare
professionals, and pharmaceutical industry representatives, provided additional evidence on the feasibility and suitability of OBP schemes
Understanding what aspects of health and quality of life are important to peopleOffice of Health Economics
Poster presentation from the EuroQol Plenary Meeting 2019, Brussels, Belgium. By Koonal Shah, Brendan Mulhern, Patricia Cubi-Molla, Bas Janssen, and David Mott.
Koonal presented as part of an organised session on ‘moving beyond conventional economic approaches in palliative and end of life care’. He summarised the empirical evidence on the extent of pubic support for an end of life premium, before discussing some novel approaches that have been used in recent studies. His presentation was discussed by Helen Mason of Glasgow Caledonian University.
Author(s) and affiliation(s): Koonal Shah, Office of Health Economics
Event: iHEA Congress
Date: 17/07/2019
Location: Basel, Switzerland
Assessing the Life-Cycle Value Added of Second Generation Antipsychotics in S...Office of Health Economics
This research presented in a poster at HTAi 2019, Cologne (Germany) by a team of OHE and IHE researchers, estimates the value added by second generation antipsychotics over their life-cycle in the UK and Sweden. It concludes that considering the entire life-cycle, the value added by SGAs to the system is higher than the expected value estimated at launch. P&R decisions should consider how to measure, capture and take into account the value added by medicines over the long-run.
Author(s) and affiliation(s): Mikel Berdud (Office of Health Economics, London), Niklas Wallin-Bernhardsson (Institute for Health Economics, Stockholm), Bernarda Zamora (Office of Health Economics, London), Peter Lindgren (Institute for Health Economics, Stockholm), Adrian Towse (Office of Health Economics, London)
Event: HTAi 2019 Annual Meeting
Date: 18/06/2019
Location: Cologne, Germany
There is growing recognition that HTA and contracting systems for antimicrobials need to be adapted to help fight the threat of antimicrobial resistance (AMR), but there is little agreement on how. This poster reports findings from a literature review, expert interviews and face-to-face discussions at a Forum on the current HTA and payment systems for antibiotics across Europe and a number of recommendations for adapting these systems to respond to the challenges of AMR.
Author(s) and affiliation(s): Margherita Neri (OHE) Grace Hampson (OHE) Christopher Henshall (OHE visiting fellow, independent consultant) Adrian Towse (OHE)
Event: HTAi annual conference 2019
Date: 18/06/2019
Location: Cologne, Germany
Assessing the Life-cycle Value Added of Second-Generation Antipsychotics in S...Office of Health Economics
This study aims to guide access decisions and drive the discussion on access and price, through recognition of the dynamic nature of value added by pharmaceutical innovation over the long-run. The analysis of the life-cycle value of risperidone estimates the value generated in the UK and Sweden. Results show that health systems were able to appropriate most of the life-cycle value generated, and this is larger than estimated at launch.
Author(s) and affiliation(s): Mikel Berdud(1), Niklas Wallin-Bernhardsson(2), Bernarda Zamora(1), Peter Lindgren(2), and Adrian Towse(1) (1) Office of Health Economics (2) The Swedish Institute for. Health Economics
Event: XXXIX JORNADAS DE ECONOMÍA DE LA SALUD
Date: 12/06/2019
Location: Albacete, Spain
Prescribed Specialised Services (PSS) Commissioning for Quality and Innovation (CQUIN) schemes were launched in 2013 in England with the aim of improving the quality of specialised care and achieving value for money. During this presentation, Marina Rodes Sanchez described the key features of the schemes and discussed its strengths and weaknesses based on international pay-for-performance literature.
Author(s) and affiliation(s): Yan Feng, Queen Mary University of London; Søren Rud Kristensen, Imperial College London; Paula Lorgelly, King’s College London; Rachel Meacock, University of Manchester; Marina Rodes Sanchez, Office of Health Economics; Luigi Siciliani, University of York; Matt Sutton, University of Manchester
Event: XXXIX Spanish Health Economics Association Conference
Date: 12/06/2019
Location: Albacete, Spain
In this session, Meng Li sets out estimates of real option value for drugs arguing that option value matters and can be calculated. Adrian Towse sets out likely payer concerns about incorporating real option value into decision making. Meng Li responds to these concerns. Jens Grueger sets out how industry considers investment opportunities, arguing that if patients (and society) have preferences these need to be reflected in P&R decisions.
Author(s) and affiliation(s): Meng Li, Postdoctoral Research Fellow, Leonard D Schaeffer Center, University of Southern California, Los Angeles, CA, USA. Adrian Towse, Emeritus Director, Office of Health Economics, London, UK Jens Grueger, formerly Head of Global Access, Senior Vice President at F. Hoffmann-La Roche
Event: ISPOR 2019
Location: New Orleans, USA
Date: 21/05/2019
MCDA OR WEIGHTED CEA BASED ON THE QALY? WHICH IS THE FUTURE FOR HTA DECISION ...Office of Health Economics
In this ISPOR session Chuck Phelps and Adrian Towse debated the case for and against using MCDA to support HTA decision making, as compared to weighting or augmenting a QALY based ICER approach. Chuck Phelps argued for use of MCDA, Adrian Towse for weighting the QALY. Nancy Devlin set the scene and moderated.
Author(s) and affiliation(s): Nancy Devlin, Director, Centre for Health Policy, University of Melbourne, Australia Adrian Towse, Emeritus Director, Office of Health Economics, London, UK Chuck Phelps, University of Rochester, Rochester, NY USA
Event: ISPOR 2019
Location: New Orleans, USA
Date: 21/05/2019
This presentation by Morris Kleiner (University of Minnesota), was made during the discussion “Competition and Regulation in Professions and Occupations” held at the Working Party No. 2 on Competition and Regulation on 10 June 2024. More papers and presentations on the topic can be found out at oe.cd/crps.
This presentation was uploaded with the author’s consent.
Acorn Recovery: Restore IT infra within minutesIP ServerOne
Introducing Acorn Recovery as a Service, a simple, fast, and secure managed disaster recovery (DRaaS) by IP ServerOne. A DR solution that helps restore your IT infra within minutes.
This presentation, created by Syed Faiz ul Hassan, explores the profound influence of media on public perception and behavior. It delves into the evolution of media from oral traditions to modern digital and social media platforms. Key topics include the role of media in information propagation, socialization, crisis awareness, globalization, and education. The presentation also examines media influence through agenda setting, propaganda, and manipulative techniques used by advertisers and marketers. Furthermore, it highlights the impact of surveillance enabled by media technologies on personal behavior and preferences. Through this comprehensive overview, the presentation aims to shed light on how media shapes collective consciousness and public opinion.
Sharpen existing tools or get a new toolbox? Contemporary cluster initiatives...Orkestra
UIIN Conference, Madrid, 27-29 May 2024
James Wilson, Orkestra and Deusto Business School
Emily Wise, Lund University
Madeline Smith, The Glasgow School of Art
0x01 - Newton's Third Law: Static vs. Dynamic AbusersOWASP Beja
f you offer a service on the web, odds are that someone will abuse it. Be it an API, a SaaS, a PaaS, or even a static website, someone somewhere will try to figure out a way to use it to their own needs. In this talk we'll compare measures that are effective against static attackers and how to battle a dynamic attacker who adapts to your counter-measures.
About the Speaker
===============
Diogo Sousa, Engineering Manager @ Canonical
An opinionated individual with an interest in cryptography and its intersection with secure software development.
Have you ever wondered how search works while visiting an e-commerce site, internal website, or searching through other types of online resources? Look no further than this informative session on the ways that taxonomies help end-users navigate the internet! Hear from taxonomists and other information professionals who have first-hand experience creating and working with taxonomies that aid in navigation, search, and discovery across a range of disciplines.
Eureka, I found it! - Special Libraries Association 2021 Presentation
Next_generation_sequencing_AKT_Nov14
1. Adrian Towse, Director of the Office of Health
Economics, London, UK
3rd Annual Health Economics & Personalised Medicine
Symposium, Amsterdam • 13th November 2014
Challenges in the development and reimbursement of
personalized medicine:
Next Generation Sequencing: An HTA
perspective on the implications for drug
reimbursement?
2. Next Generation Sequencing: Implications For Drug Reimbursement?
13/11/2014 2
Agenda
• What is Next Generation Sequencing (NGS)?
• Potential uses and value of NGS
• Are we ready or not quite yet in oncology?
• Hypothetical examples of NGS in practice
• What value can NGS offer in HTA terms?
• Where will the evidence of clinical utility come
from?
• Organising to get the best value from NGS
• Summary points
3. Next Generation Sequencing: Implications For Drug Reimbursement?
13/11/2014 3
Definition: What is Next Generation
Sequencing?
A substitute for the currently more common Sanger sequencing1.
What is new in Next Generation Sequencing?
They are distinguished by their ability to rapidly examine many
genes simultaneously, using a single test.
The main clinically relevant forms of NGS are2:
• Exome and targeted sequencing: targeted at specific genome
locations.
• Whole genome sequencing: sequence of the entire genome.
The four main advantages of NGS over classical Sanger
sequencing are1:
• Speed; cost of sequencing; sample size; accuracy.
Sources:1The Wellcome Trust (2014), 2The European Bioinformatics Institute (2014)
4. Next Generation Sequencing: Implications For Drug Reimbursement?
13/11/2014 4
NGS is often seen as a disruptive innovation because of the
significant decreases in cost of analysing many gene sequences in
parallel substituting for a range of “traditional” tests
Three drivers of the cost of NGS:
1. The pre-analytics and assay
2. The bioinformatics platform. The assay generates a set of data,
which is then visualised and analysed using the software
developed to provide the informatics platform.
3. Evidence base for clinical utility and the need to convey the
information to the patient and make treatment choices
Currently only the cost of component 1. is clearly declining.
Source: 1Adapted from Deverka, P. A., & Dreyfus, J. C. (2014)
What are the potential uses
and value of NGS? (1) 1
5. Next Generation Sequencing: Implications For Drug Reimbursement?
13/11/2014 5
What are the potential uses
and value of NGS? (2)
The value of NGS is partly dependent on the use that one
makes of it.
NGS can be used for1:
1. Diagnosis
2. Treatment decisions and monitoring
3. Detection of future risk (although this raises ethical and
data security issues as well as economic issues)
4. Reproductive planning (preconception and prenatal
screening)
5. Newborn screening (which could also raise issues)
We look at disease/treatment targeted gene panels (1.& 2.)
Source: 1Phillips, K. et al., (2014)
6. Next Generation Sequencing: Implications For Drug Reimbursement?
13/11/2014 6
What are the potential uses
and value of NGS? (3)
NGS more generally thought about as covering:
1. Targeted sequencing
2. Whole exome sequencing
3. Whole genome sequencing
I focus only on 1.
2. and 3. give rise to issues of:
• “Big Data” analytical challenges
• Storage, privacy, and data management
• Ethical issues, e.g. secondary findings
Source: 1Phillips, K. et al., (2014)
7. Next Generation Sequencing: Implications For Drug Reimbursement?
13/11/2014 7
NGS in clinical decision making: are we ready
or not quite yet? The example of Oncology
• “Although many of the therapeutic implications of NGS involve clinical trial
participation, NGS is ready for the clinic. Some clinicians would argue it
already is in the clinic. Our focus now should turn to bringing this
revolutionary, therapy-altering and prognostic technology to all patients in
an efficient, affordable way.” Kathleen Harnden and Kimberly Blackwell
• “Accordingly, for today’s clinical practice, single gene assays suffice.
However, as NGS become cheaper, it may be a simpler way to perform
diagnostics on the small number of tumours in which several mutations,
translocations or deletions are of proven benefit in decision-making, such as
lung cancer or haematological malignancies.” Debu Tripathy
• “In summary, then, somatic mutation profiling by NGS is not necessary
for deployment of approved genomically-directed treatments and is not yet
at the point where it can be used to direct off-protocol treatment.
Profiling may be useful as a screening tool to determine trial eligibility but,
for most patients”. Mark Robson
Source: 1Tripathy, D., Harnden, K., Blackwell, K., & Robson, M. (2014).
8. Next Generation Sequencing: Implications For Drug Reimbursement?
13/11/2014 8
What could NGS look like in practice? (1)
Treatment selection in Lung cancer1:
• KRAS Mutation: have been associated with response or
resistance to particular therapies
• EGFR Mutation: predicts for sensitivity to EGFR tyrosine kinase
inhibitors (TKIs)
• ALK translocation: presence of an ALK translocation strongly
predicts for sensitivity to ALK tyrosine kinase inhibitors
• MET amplification: recognized as one of the potential molecular
mechanisms of acquired resistance to EGFR-TKIs
• ROS-1 fusions: can be used to offer targeted treatment with
criozitinib.
Source: 1Korpanty, G. J., Graham, D. M., Vincent, M. D., & Leighl, N. B. (2014)
9. Next Generation Sequencing: Implications For Drug Reimbursement?
13/11/2014 9
What could NGS look like in practice? (2)
Dosage adjustments and treatment selection in
Schizophrenia:
• CYP4501: information about CYP450 genotype can be used to
group patients in ultra rapid, moderate and slow metabolisers
adjusting the treatment dose of drugs such as risperidone
accordingly.
• COMT2: polymorphisms in the COMT gene determine likelihood
of response to certain antipsychotics.
• SULT4A1-1 Haplotype 13: identifies a subset of patients with
lower risk of hospitalisation when treated with certain drugs
compared to others.
Sources: 1Ravyn, D., Ravyn, V., Lowney, R., & Nasrallah, H. A. (2013). 2Gupta, M. et al. (2009).
3Liu, Q. et al. (2012).
10. Next Generation Sequencing: Implications For Drug Reimbursement?
13/11/2014 10
What are the potential sources of HTA value
from use of NGS to select treatment options? (1)
Value
1. Reducing
drug
adverse
effects
2. Reducing
time delays
in selecting
optimal Tx
3.Increasing
adherence
or
willingness
to start Tx
4. Enabling Tx
effective in a
small fraction
to be made
available
5.Reducing
uncertainty
about value
Source: Garau et al. (2013)
11. Next Generation Sequencing: Implications For Drug Reimbursement?
13/11/2014 11
What are the potential sources of HTA value from
use of NGS to select treatment options? (2)
Reduced assay test costs, increased speed and
accuracy
• Replaces a suite of tests – but we may not have
needed them all
• Some reduction in time – this matters
• May avoid starting on the incorrect therapy
• Increased accuracy enables better patient
stratification, fewer false positives and false
negatives
Health and cost implications unclear. Positive
health gain but higher costs? Is it cost effective?
12. Next Generation Sequencing: Implications For Drug Reimbursement?
13/11/2014 12
Towse A., et al. (2013)
Challenge: where will the evidence of
clinical utility come from?
13. Next Generation Sequencing: Implications For Drug Reimbursement?
13/11/2014 13
Table 1. Sources of clinical utility evidence for decision-making in the nine case studies.
Marker Main Study Design
Study size
(patient numbers)
Sponsor Decision-making Impact
Breast cancer recurrence
(a) Oncotype DX®
and (b)
MammaPrint®
(Prognostic/predictive in BrCa)
Retrospective RCT
cohorts
RCTs
(a) 688 [4] +651 [5] +895 [6]
(b) Prognostic: 117 [9] +295
[10] +307 [11]
+123 [12] ,
Predictive: 241 [13]
(a) 11248 [7]
(b) 6600 [14]
Diagnostic
manufacturer
Public research body
Public research
bodies
Generating clinical utility can yield
inclusion in clinical guidelines and
positive reimbursement decisions at a
favourable price for test developers.
HER2
(Trastuzumab in metastatic and
early stage BrCa)
RCTs
469 [16]
3676 [19]
Drug developer
Drug developer
Positive reimbursement decision for
drug-diagnostic in a specific
subpopulation based on health gains and
cost-effectiveness.
EGFR mutations
(1st line TKI treatment in
NSCLC)
RCTs
RCTs
1217 [25]
165 [26]
173 [27]
Drug developer
Drug developer
Drug rescued because of a predictive, ex
post companion diagnostic.
Obtained first line indication
KRAS mutations
(Anti-EGFR monoclonal
antibodies in CRC)
Retrospective cohort
analysis of an RCT
1198 [39]
Drug developer and
Public research body
Decision-makers are willing to consider
evidence generated ex post as sufficient to
change recommended treatment protocols.
BCR-ABL transcript
(TKI treatment in CML)
RCT 1106 [42] Drug developer
Actionable, clinical information allowed
for full incorporation into clinical
guidelines; however, issues with inter-
and intra-laboratory variability may
impact patient management thus health
outcomes.
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Table 1. Cont.
Marker Main Study Design
Study size
(patient numbers)
Sponsor Decision-making Impact
CYP2C19
(Clopidogrel in ACS)
Retrospective RCT
cohort+Healthy
volunteers
Prospective cohort study
Proof-of concept RCT
1477+162 [52]
4471 [57] (Terminated early)
187 [58]
Public research body
Payer
Diagnostic
manufacturer
The clinically significant and validated
predictive effect would allow for health
care efficiencies in the treatment of ACS.
New POC test could improve
implementation in clinical practice.
HLA-B*5701
(ABC in HIV)
Retrospective case
control
RCT
408 [59]
1956 [59]
Drug developer
Drug developer
Prospective screening for first-line
treatment is cost-effective in specific
sub-populations. Treatment guidelines
recommend abacavir only if patients have
tested negative for HLA-B*5701.
Viral load
(Pegylated interferon and
ribavirin in hepatitis C)
Retrospective analyses of
RCT data
1016 [61]
260 [62]
Drug developer
Public research body
Testing becomes fundamental for
predicting treatment outcome, reducing
treatment side-effects and avoiding futile
treatment and subsequent costs in non-
responding patients.
PreDx® DRS
(Risk in Type 2 diabetes)
Retrospective analysis of
a sub-cohort of a lifestyle
interventional trial
6784 [67,68]
Assay developer (trial
funded by a public
research body)
Although the score has been proven
significantly better than other available
methods and similar to the gold standard,
uptake has been very limited. Data may
not be generalisable to the whole
population, and payers may not want to
cover the test in addition to fasting
glucose testing.
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Organising to get the best value from NGS
• Need to have HTA of NGS where accuracy and
clinical utility are assessed
• “Home brews” present a quality challenge.
Certification and inspection are key.
• Willingness to use commercial “kits” is
important if they offer better value.
• If NGS value is there in theory it is likely that it
is only realised in practice in a few specialised
treatment locations
• Need to introduce HTA for NGS and MDx
16. Next Generation Sequencing: Implications For Drug Reimbursement?
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Summary Points
• There are some advantages of NGS compared with current
practice in terms of speed, cost, sample size needed and
accuracy.
• But NGS is not (yet?) transformative. The value of NGS does not
come from multiple testing, but from the informatics and
evidence of clinical utility. These costs are not falling.
• Demonstrating clinical utility is likely to be a challenge for NGS
providers.
• However, use of NGS may well enable drugs to be better
targeted, reducing use of ineffective drugs and adverse events,
saving time, and improving health gain. But costs may go up.
• Need HTA for NGS and MDx – pay for value
• Using NGS effectively may well involve some concentration of
cancer service provision in specialist centres.
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