This first-of-its kind calibration study on genomic interpretation surveyed over 55 industry leaders across twelve healthcare segments. Interview transcripts were reviewed by a panel of experts representing all disciplines key to incorporating genomic interpretation into patient care. The panel developed a comprehensive set of findings and recommendations to accelerate the advance of genomics into day-t0-day healthcare.

The year-long project was an absolute joy to co-direct and we’re thankful to all 55 participants and 6 members of the panel.  The full release and report are available here.

Protection of data is a paramount concern for us at GenomeQuest. We’ve been protecting the data of our patent sequence search customers for over a decade. HIPAA provides an even higher standard for us to have reached to ensure that their data is locked down and treated as if it were personally identifiable patient information.

It also strengthens our core research NGS product line, further tightening the security we already provide to academic labs, pharma companies, and seed companies around the world.

Finally, we recognize that so much of the promise of high-throughput sequencing lies in the clinic. But when we looked out at the many companies claiming to offer clinical-grade genomics capabilities, we were struck by the degree to which HIPAA was simply disregarded from the conversation.

Today we are the only sequence informatics company to provide a HIPAA-compliant cloud-based solution across all of our applications and services. GenomeQuest is eager to continue to support genomics’ dash to the clinic, and to strive for the highest levels of security for all of our customers and their associates.

The meeting was absolutely dominated by NGS. From Madhuri Hegde’s short course on NGS (which ran for seven hours) to Wayne Grody’s strong endorsement of genome-wide analysis, to the ACMG’s new policy statement on genomics, there is no question that the age of the diagnostic genome is upon us, and that the FACMGs are leading the way.

My takeaways from the meeting:

• Gene panels are the story of the year. Every lab is launching one. A smaller percentage is announcing exome sequencing tests this year. Only one (Harvard Partners LMM) has announced a whole genome diagnostic screen this year, although it is not yet launched.
• There was a palpable sense of panic by those lab directors who hadn’t yet made their investment in their NGS machine.
• And a similar panic by those who had the sequencing capability but not the interpretation. (Of course GenomeQuest was happy to help and made lots of new friends!)
• I’m surprised that even as ACMG is widely embracing genomic diagnostics and medicine, that they had a very poor representation of cancer genomics. Cancer is a disease of the genome. Is ACMG resigning cancer to AMP so soon?
• The ION Torrent seems to be making in-roads over the MiSeq. Sentiment varies as to why, but the 318 chip is getting favorable reviews and people like the price. Lack of strong paired-end support doesn’t seem to get in medical geneticist’s way. Maybe it’s the big bus that LIFE drives into the exhibit hall.
• Just as the ION is catching on, so is its producer, LIFE Technologies, building cancer panels to compete with its very customers – the labs that are buying ION machines. Seems they may not have learned from Illumina’s mistakes.
• I continually marvel at the degree to which academic and scientific leaders can collaborate at these meetings while simultaneously running labs that compete directly with one another. Never have I seen such well-behaved co-opetition.
• There are a growing number of initiatives to create clinical-grade interpretation databases, propagating an ever-increasing confusion around the line between commercial, government, and academic intellectual property. This more than anything is a shame – clinical knowledge of the genome should be a public resource.
• I heard widespread resentment about the NCBI’s Genetic Testing Registry as a replacement for GeneTests.
• Genomes are moving rapidly into the EMR.
• Reimbursement is not so big an issue as one might expect. Labs are either stacking CPT codes for panels, or quoting and charging a flat institutional price (and passing along the reimbursement problem to the ordering institution). Some labs are launching tests without knowing how and whether they’ll get reimbursed; they’re being granted permission to launch these new diagnostics at their hospital’s own expense so that they stay relevant. Everyone is looking forward to the new codes which will reimburse larger numbers of amplicons, but it’s not slowing down test launch right now.
• Where are the payors? Still waking up to this revolution, I think. If I were a payor, I’d be bolting on genome diagnostic capabilities wherever possible. Not only are they faster, cheaper ways to getting to the same result as expensive Sanger tests, they generate a more comprehensive body of data that can be used to determine which treatments correspond to which genotypes to create low-cost strong outcomes.

And the beat goes on. Real patients are benefiting from larger genetic screens, faster turn around times, and cheaper costs thanks to NGS. And the databases of phenotype / genotype relationships are growing. Congrats to the ACMG for carrying the torch.

In support of this initiative, I had the distinct pleasure of attending the International Patent Information (IPI) Conference in Barcelona this month.

My primary observations:

1. If the program management was any indication, the EU IP business is vibrant and in good hands. All the sessions and speakers were informative, thoughtful, and business-minded.  And I found the leadership and energy of Ian Sinclair, a veteran of Pfizer, and Gerhard Fischer, Syngenta, to be especially compelling — wonderful to meet and exchange ideas with them.

2. The most informative (non-GenomeQuest of course) vendor presentation, in my opinion, came from Questel.  Renauld Garat communicated and showed a dizzying array of important and impressive advancements to what is already an industry-leading set of patent information resources.  Also great to meet his distinguished colleagues Martine Massiera, Anthony Gelot, and Roland Kissler.

3. The most informative user presentation, in my opinion, came from May Peng of Sanofi Aventis. Her dynamic performance offered practical advice of researching patent and prior art information coming from China, clearly an emerging world leader in patents (e.g., I understand that 1/3 of pharma patents now start in China).

4. Important to catch an IP5 update from Peter Kallas of BASF. IP5 is a consortia of the 5 largest patent offices: US, EU, China, Korea, and Japan.  With 10 Foundation Projects, they seek to build a common platform and, specifically, have a 2020 goal to build a common classification system for US and EU.

5. Also great to hear an overview from Mike Fuller, from San Diego law firm Knobbe Martens, on the American Invents Act, which has significant implications to EU patent experts. I understand that it brings two significant changes to U.S. patenting in 2013: a. the first-to-invent requirement becomes first-to-file and b. prior art is broadened to include more materials and international disclosure.

6.  Overall, in various discussions and in the career development workshop, I developed a far better appreciation for the painful time/document crunch experienced by patent experts. On the one hand, they have increasingly tighter schedules to meet, while, on the other, their global searches are producing longer candidate lists and, at the end of the day, taller and more daunting stacks of documentation to read.

(On the last point, GenomeQuest is hard at work on this precise problem. We want our interactive research environment to empower patent experts to quickly reduce search results to key targets, slash unnecessary research, and focus attention/reading on the materials that matter most.  For us, the overall goal is to help patent experts meet or beat their schedules and deliver high-quality, accurate reports.)

For years preceding the completion of the Human Genome Project, genome researchers were trumpeting the revolutionary breakthroughs, discoveries, and treatments that would result from this work.  When this failed to immediately materialize, due to a gross underestimation of the true complexity of the human body and disease -  investors, media, and the general public quickly lost interest.  Fast forward 10 years, and it appears that the genomics industry is gun shy choosing to talk about their tools and not how an Ashkenazi Jewish rabbi has to tell two in-love members of his synagogue that they can’t marry because genetic testing says they are both carriers for canavan disease.

From my position here at GenomeQuest, I have been fortunate to work with leading edge customers in the clinical space who are using next generation sequencing for disease diagnostics today, not tomorrow and not after “we figure out how to deal with the data”.   It’s great to tell stories about terabytes and petabytes of data, but until we can translate that into treatments and prescriptions it remains a distant pipe dream in the public’s eyes. After all, isn’t that why we build these tools? Not to talk about how much data they can churn out but how they can be used  to affect people’s everyday lives.

Talk about night and day!

While it’s reasonable to question if and when core reseachers will understand the full extent of NGS data, it’s equally reasonable to get excited about applying what we know already.  Simply stated, I would argue that diagnostics — specifically consolidated molecular testing (CMDx) — is a clear killer app for NGS.

No doubt, labs are aching for and advancing to CMDx today.  And, no doubt, their patients are realizing undeniable and measureable rewards of faster/better/cheaper diagnostics.  Moreover, a standard platform (NGS) creates a wonderfully virtuous circle for them to provide increasingly better diagnostics for more and more diseases.

When it was introduced, the Mac was an amazing technology looking for a critical mass application — then along came desktop publishing and computing history was changed forever. I think the same opportunity exists for NGS, CMDx, and healthcare.

As evidence, I offer you real world “faster/better/cheaper” excerpts from two simple questions in our grant applications:

– What are the health benefits to your patients?
– What are the business benefits to your labs and partners?

See if you tend to agree.

Below are my top “takeaways” from the conference and workshop:

1. 80% say sequencing value will be in “interpretation”

In the case study on “sequencing technology” run by Richard Hamermesh of HBS, the audience was asked:

In 2021, which of the following sequencing segments will be strongest: hardware, consumables, service, or interpretation?

The answer: eighty percent said interpretation.  The viewpoint that interpretation of the data will be challenge #1 in PM was repeated by several presentors, including: Lee Hood of ISB, Stephen Spielberg of the FDA, Dave King of Labcorp, John Nierderhuber of Inova, and Hakan Kakul of Pfizer.

Immediate good news here: I think that we’re getting over the initial fear of the whole-genome sequencing (WGS) “ocean of data“.  Yes, we’re understanding that WGS is a technology and that we don’t have to digest everything it produces — we can focus on the data of most interest and use.  Just like we don’t have to watch all 800+ TV channels to justify and enjoy cable service, there’s amazing value in “targeted interpretation”.  And, over time, we’ll learn more and expand our targets.

2. PM industry integration is happening.

In order to take hold, PM requires a tighter integration of the healthcare pieces — otherwise, benefits won’t accrue to the investors and the new economic wheel won’t turn.  Here, I am encouraged as I see a combination of top-down and bottom-up change agents at work.   Industry leaders, such as PMC/FDA/VA,  are proactively creating an environment for motivating and guiding this integration.  And, industry players — including VCs, Dx companies, labs, sequencing vendors, and payors — are working amongst themselves to understand and incrementally effect this integration.

(BTW, progress and thoughts on the regulation front: we heard from many Dx leaders that the FDA is open-minded and willing to be led in PM –- so meet early and often in the development/approval process.)

3. Our aim should be squarely on whole-genome sequencing.

While the intemediate technologies of gene-panels and whole-exome sequencing will offer substantial rewards and lessons learned, the economies-of-scale and medical revelations granted by WGS justify that our major investments and best minds focus on this final destination.  After all, according to Partners Scientific Director Scott Weiss, “WGS will render targeted sequencing obsolete in 4 years“.

As breathtaking as the falling cost-curve of sequencing has been in the past decade, I think we’ll be equally awed by sequencing cost and quality improvements in the next few years.   Specifically, I believe that the market force of an expanding set of 3rd generation vendors and technologies (over 10 listed in HBS case study) will enable whole new PM applications and create whole new markets.

4. VCs and Wall St. are becoming increasingly supportive of PM/MDx.

I appreciated the inflective thoughts of Brook Byers of Kleiner (“we are entering the early days of PM“) and Amanda Murphy of William Blair (“we’re at an economic peak of uncertainty in PM“).  Byers was most enthused about the Dx side and influenced by long-term, wellness managers and payors.  Also indicating enthusiasm are the funding of the above 3rd generation vendors and warming of MDx acquisition activity, including the $.5B acquisition of Clarient by GE Heathcare.

One of the more interesting dynamics as we arc from genomics for drug/disease research to clinical application is the associated pivot from a largely foundation-funded market to a commercial market — aiming to improve and provide economic value to a $5T global healthcare market.   In my opinion, this adjustment to a commercial market is where much of the management challenge and opportunities lies.

5. The industry needs to agree on an global “atlas” of genotype/phenotype database.

This is front and center of many thoughful PM talks over the past year.  At PMC, I began to see significant movement in this direction: a. organizations planning the integration of genomics with the EHR which will speed genotype/phenotype associations, b. teams structuring phenotype-rich, genotype-enabled clinical trials, and c. a proposal for a standard platform for research labs to establish and share clinical evidence.

6. Much effort/$ should be put into enabling PM at community hospitals

Gregory Feero of NHGRI thought it worth noting — from a conference operating deep inside HMS — that 95% of heathcare happens outside academic medical centers.  Well played.  One example of progress is the KEW Group, which is building a national network of PM-based community cancer care centers.

7. The Dx industry is preparing its economic case for MDx.

On the one hand, Dx informs 70% of medical decisions and MDx holds immense promise for fundamentally improving healthcare.  On the other, Dx amounts to just $40B of the $5T healthcare industry and the assigned skeptic at the conference (artfully played by Dr. Ezekiel Emanuel) waged a blistering attack that PM makes little/no economic sense.

What gives?

Clearly, MDx is undervalued in the healthcare industry — our payment system favors therapy/technology over diagnostics/interpretation.  One giant step forward would be to argue the economic case for MDx.  And I foresee the PM Coalition and industry preparing two pieces: a holistic, multi-factor economic argument for MDx to spur reimbursement change and associated decision support to inform day-to-day care.

8. We continue to be guided and inspired by Dr. Lee Hood

In accepting his leadership award, Lee Hood offered a wonderful combination of science vision and medical practicality to guide the path forward.  In particular, he was most excited about: a. family-based studies, proven to reduce errors by 70% and shrink solution space by 100x, b. analysis of single cells, and c. system-level considerations and tools, required  to addresss the “grand challenge” of PM (complexity).

Overall, it provided a wonderful and thorough update on the state of genetic research, practice, and plans – bravo to the show organizers and all presenters!

Below are the top seven thoughts I heard in my sessions and around the conference:

1. “We’re all a brotherhood of mutations”

… a wonderful expression of community by Michael Hayden of Canada’s Center for Molecular Medicine that was met with loud applause in the Medical Genetics panel debate.  It was a welcome counter to Dr. James Watson’s disturbing “some people are genetic losers” from the starting panel the day prior.

2. “I was assigned this case by a computer and it was a stroke of great providence that my clerk had a PhD in molecular biology”

…  testimony from U.S. District Court Judge Sweet who, of course, ruled to invalidate the Myriad BRCA patents.  The audience in this “Who Owns the Gene” panel was wowed with his presence and clearly leaned anti-patent — best expressed by a member who proclaimed “Darwinian selection will eliminate gene patents”.

3. “Targeted NGS for the clinic is ‘ready-to-go’”

… a confident claim made by Ming Qi of the Zhejiang Medical School and buttressed by Joris Veltman who is today using NGS for clinical work in blindness at the University of Nijmegen.  Hayden raised serious warnings of over-promises and incidental consequences but the Medical Genetics debate settled on “acting on what we know” and coined the handy term “targeted interpretation”.  Representing the general MDx market and in related conversations, Dr. Roberta Pagon of GeneTests suggested that consolidated gene panels would be a common entry point to NGS for many labs.

4. “This would have saved $7M and prevented 400 adverse events”

… the result of a retrospective PGx simulation by Vanderbilt on 53K patients over a six month period.  Dr. Schildcrout also reported that ADR is the 4th largest cause of death in the US, killing 106K patients per year, and that PGx has grown from a start by the FDA in 2007 to over 100 drugs now carrying PGx labels.  Dr. S. Qin reported that China now runs a nation-wide network to collect and share adverse events.

5. “Physicians don’t want to learn it ALL, they want to learn ENOUGH”

… telling observation made by Dr. Farndon of the UK Genetics Education Center, which has been training physicians in genetics for over six years.  ACHG president Lynn Jorde stressed the need for this continuing education in U.S., noting that only 26% of physicians have a genetics education and only 10% make use of PGx.  Good news on when that happens — MEDCO reported that, in a Labcorp-supported study, 50% of physicians took advantage of a piloted PGx system when deciding treatment and 40% of the time changed treatment when directed.

6. “We all seek a global phenotype/genotype database”

… perhaps the most resounding agreement by the Medical Genetics panel and declared by Han Brunner of the University of Nijmegen (and one of the better moderators I’ve come across).  In separate discussions with lab leaders Heidi Rehm (Partners) and Madhuri Hegde (Emory), it’s clear to me that, while such a “mother of all databases” will be some time coming, indeed academic/commercial collaborations will make transformational and practical progress for health care in this direction in 2012.

7. “Give patients the choice”

… not exactly a quote but my paraphrasing of the ethics panel consensus on the issue of informing patents of incidental findings from whole-genome sequencing.  More generally, I’m a believer that, as more personalized medicine services emerge and news of their life-changing benefits escapes, patients will demand more information, become the fastest learning group in health care, and serve as a positive and major force in this disruption.

Oh, and…

8. “Maybe we spend a couple weeks in Burlington every winter”

… from a quite smitten skier and wife, after our stay in northern VT on the drive from Boston.

]]> http://blog.genomequest.com/2011/10/top-7-thoughts-heard-at-ichg/feed/ 0 http://blog.genomequest.com/2011/09/personalized-medicine-for-cancer-on-cbs-evening-news/ http://blog.genomequest.com/2011/09/personalized-medicine-for-cancer-on-cbs-evening-news/#comments Fri, 23 Sep 2011 18:51:35 +0000 Tony Flynn http://blog.genomequest.com/?p=456 here [...]]]> On the 40th anniversary of the National Cancer Act, the American Association of Cancer Research (AACR) this week issued its first “Cancer Progress Report”.

It’s an outstanding, 84-page narrative that outlines the progress in our understanding/treatment of cancer and the criticality of genomics in transforming patient care going forward.

You can download the full report here and watch the CBS Evening News story here.

Congratulations to the AACR on this clear and powerful piece.

They have much to be proud of – the use of VistA has enabled the VA to reach a pharmacy prescription accuracy rate of almost 100%, and the VA outperforms most public sector hospitals on a variety of criteria, enabled by the implementation of VistA. VA hospitals using VistA are one of the few hospital systems that have achieved the qualifications for HIMSS stage 7, the highest level of EHR integration. The goal is to create a usable, next generation EHR that can anticipate and be flexible enough to accommodate where clinical informatics will be headed over the next decade, and the big target is genomic data from the VA’s own Million Veterans Program (MVP).

The ambitious MVP is an ongoing initiative, according to Veterans Affairs Eric K. Shinseki, “It is my honor to join with so many fellow Veterans in keeping VA at the leading edge of genomics research.  This innovative research program will support VA’s mission to provide Veterans and their families with the care they have earned.” The Million Veteran Program is a trailblazing VA effort to consolidate genetic, military exposure, health, and lifestyle information together in one single database.  The database will be used only by authorized researchers with VA, other federal health agencies, and academic institutions within the U.S.—in a secure manner—to conduct health and wellness studies to determine which genetic variations are associated with particular health issues.  By identifying gene-health connections, the program could consequentially advance disease screening, diagnosis, and prognosis and point the way toward more effective, personalized therapies.

In a recent workshop held at the prestigious Institute of Medicine, called “Integrating Large-Scale Genomic Information into Clinical Practice”, several key scientists and clinicians from Genome Centers described the evolution of clinical genetic diagnostics – from gene test panels to whole exome sequencing to whole genome sequencing. With the precipitous drop in the cost of human genome sequencing, the strong recommendation from participants at the workshop was, although we have interim genome-based diagnostic tests, within 2-3 years everyone will be performing whole genome sequencing and analysis because it reveals so much more information about the correlation between genetic variation and disease phenotype^1,2. This mantra is now resounding within the VA’s clinical MVP program, which is evolving with the technology:

¹ Ley at al (2008) DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.  Nature 456, 66-72 (6 November 2008) | doi:10.1038/nature07485.

² Welch et al (2011) Use of Whole-Genome Sequencing to Diagnose a Cryptic Fusion Oncogene.   JAMA, April 20, 2011. 305 (15): 1577-1584