Interview with Dr Eddie Blair, PhD, by Claire Raison (Commissioning Editor)
Dr Eddie Blair is Managing Director of Integrated Medicines Ltd (Cambridge, UK), a company he formed in 2003 to enable precision medicine by combining diagnostic testing with new and existing medicines. Dr Blair has raised angel and private equity investments in excess of £12 million, has published over 40 primary peer-reviewed papers, including a series on companion diagnostic valuation, and is named inventor on at least 12 patents. Dr Blair is a member of the Editorial Advisory Board of Expert Review of Molecular Diagnostics and speaks to the Commissioning Editor here about entrepreneurship, obstacles and potential of introducing diagnostics innovations into routine clinical practice.
What is the most promising area of your work at present?
I’m interested in how you get a new test that guides treatment into NHS. Integrated Medicines (Cambridge, UK) won a government small business research initiative (SBRI) contract from Innovate UK, which is essentially a contract to undertake work that allows the NHS to engage with innovative solution providers. We mapped a basic patient care pathway for sepsis, from reviewing clinical records, and then simulated how a point-of-care diagnostic might enhance the appropriate use of antibiotics for better patient outcomes. We’ve been doing this for about 2 years now, so it was a particular thrill to see the recent report from the Review on Antimicrobial Resistance led by Jim O’Neill recommending the use of rapid diagnostic tests to avoid unnecessary antibiotic use.[Citation1]
The simulation shows an economic benefit to a hospital of cost per patient over a year decreasing from £11,000 down to £9500, a benefit to clinical outcomes in terms of mortality reduced from 22 to 15%, and a resource benefit in that the number of high-dependency and intensive care hospital bed days dropped from around 7 days to 4 days [manuscript in preparation]. So using the point-of-care diagnostic suggests an impact on all three of these benefit parameters; our current application will focus on antibiotic stratification.
‘using the point-of-care diagnostic suggests an impact on all three of these benefit parameters’
This new SBRI funding application, if successful, will allow us to extend our mapping of the basic care pathway and simulated enhanced pathway, to then show that these simulated results translate into the ‘real world.’ In short, we want to move from simulation of the advantages of testing to looking at actual clinical outcomes. This would really provide the evidence that would drive uptake of tests that allow an optimized balance of broad- 60 spectrum and targeted antibiotics. This is at the core of the 4th O’Neill report: how to identify the patients that need antibiotics and to get the right antibiotics to them, in a timely manner.
‘This is at the core of the 4th O’Neill report: how to identify the patients that need antibiotics and to get the right antibiotics to them, in a timely manner’
What are the biggest challenges facing your field of work at present?
We’re finding that simulated evidence isn’t enough and that the UK National Health Services want real-world data. It is going to be a challenge for anyone currently working in simulation to show that they can reproduce the benefits of simulation in the real world. That reflects the broader challenge of getting the NHS to take up a new innovation. This isn’t just because of the financial aspects, it’s because everyone is so busy in the NHS – resources are indeed stretched – and despite organizations such as academic health networks and diagnostics effectiveness cooperatives, it’s really quite difficult to get innovations into the NHS, unless they are hugely and overtly beneficial.
This is seen in cancer care, for example. Some drugs, through the cancer drug fund, get into the NHS very quickly because the clinical outcomes are substantially improved and on top of that there is a budget to pay for these things. Cost is a part of it, but the problem is mainly that people are so busy in the NHS and to do something different, people need to have time to understand new technologies and new approaches and become educated in them for innovations to be adopted and integrated.
What are your hopes and predictions for precision medicine in the next 5 years?
‘Precision medicine is likely to move beyond oncology and infectious disease’
Precision medicine is likely to move beyond oncology and infectious disease into other areas that are of concern such as degenerative chronic diseases, for example, Alzheimer’s disease, rheumatoid arthritis and diabetes, as well as other diseases that are equally worthy. The hope is that precision medicine approaches will augment doctors’ decisions, rather than replacing them per se. This can already be seen in oncology where clinicians in hospital multidisciplinary teams are substantially informed by pathologists, because the latter have information from a diagnostic test that guides on the likely utility of a targeted medicine. For example, companion diagnostics for EGFR are linked to drugs such as Herceptin or Iressa; the pathologist can advise the clinician that this patient has tested positive for this biomarker, which means the patient could be treated beneficially by these drugs.
I hope that this well-informed multidisciplinary team approach is something that translates into the broader practice of health care, so that precision medicine moves beyond the two areas of oncology and infectious diseases and becomes the norm. That could be in the next 5 years, or a little longer. Within the next 5 years we should start to see a broader embracing of precision medicine, but that also relates back to the challenge of introducing innovations into the NHS.
What changes, if any, would you like to see in the EU approval and regulation of in vitro diagnostics?
The FDA is very helpful and releases a lot of guidance and regulations. Last year they put out papers about companion diagnostics and laboratory-developed tests. The EU regulators have been trying to develop new regulations for a long time. Broadly, I think the move to risk-based categorization and the new EU regulations on CE marking are probably a welcome change to people who are used to working in a highly regulated industry, such as drug development. The problem with regulations is getting the balance right. Regulation is good for big companies that can spend time and money and resources on understanding and working to regulations. However, a lot of diagnostics are developed by small- and medium-sized enterprises and the challenge for them is meeting the demands of the regulations, particularly around clinical validation, which calls for quite substantial clinical evidence beyond the current practices.
That is a challenge but I think it’s a good one, I’m all in favor or prospective clinical studies: it’s what the second phase of our proposed SBRI funding is going to do. We’re going to budget about £2million for clinical studies, which is a lot of money for a small diagnostics company. That said, this level of investment is in the range that you might get from certain other funds, such as Biomedical Catalyst, or from generous business angels or smaller venture capitalist investors.
One of the challenges in companion diagnostics is that you can’t put much on a companion diagnostic label until the accompanying drug is on the market, but you want to have the test ready to be run in labs as soon as the drug is available. There almost needs to be a pre-validation phase for companion diagnostics where there is a CE marking of the IVD in its own right, then as soon as the drug it’s to be matched with comes on the market, it would be transferred to an intended use as a companion diagnostic. This could be something that would be incredibly helpful to both the diagnostic and the pharma industry.
You contributed an Editorial to Expert Review of Molecular Diagnostics on ‘The economic value of companion diagnostics and stratified medicines’ in 2012.[Citation2] Have perspectives on companion diagnostics changed since then?
Although the price of a diagnostic and the cost of running a diagnostic test may be around £50–200, it is nonetheless a gateway to quite expensive medicines. If you’re using a test at this price to access 5% of a treatable population then you’re going to have to run 20 tests to get one prescription, which becomes close to a sizeable proportion of the price of some of the drugs; that is quite a challenging proposition. An example of this would be EGFR or ALK mutation testing.
However, in other cases, for example with KRAS- or BRAF-positive cancers or for some of the immune-oncology drugs, where at least half the patient population can be treated if they have the biomarker, it means that a $200 test has very good value if it directs appropriate use of an expensive medicine. It also works for the drug company because the right people will get the right medicine. The Health Technology Assessment (HTA) agency can also see that precisely the right population is being treated and that the pricing strategy is correct. I think that pharma companies are certainly recognizing that the test is a relatively low-cost way of getting to the right patient population and potentially premium pricing.
Things have moved forward substantially with the HTA and reimbursement. The same thing is happening in the US, since Obamacare [Citation3] has brought in accountable care organizations, which I think are going to be like the HTA in many ways, such as assessing value and determining reimbursement.
Is the best way forward for fostering technological innovations in diagnostics a balance of academia and industry working together?
Yes, that’s really what Biomedical Catalyst and such-like competitions from Innovate UK support; giving money to small- and medium-sized enterprises but encouraging them to work with academia to source the innovation. We know it works because Britain is a great place for inventing things, but isn’t always good at exploiting them, which is what British companies still need to work on.
It is particularly important that a good academic idea is allowed to flourish and become an innovative product, but at the same time, what Innovate UK does very well is it to identify those scientific or technical innovations that are great academic science, but don’t have a business future. That’s what pharma has been trying to do for years as well: pick the winners early, because investing in technologies that aren’t going to develop into products is a sunk cost and it adds to everyone’s costs in many ways. I think that’s an important point where industry and academia need to work together.
What is your proudest achievement of your career so far?
‘I like getting new businesses off the ground, and it’s great to see some ideas come through to fruition and onto the market’
I like getting new businesses off the ground, and it’s great to see some ideas come through to fruition and onto the market. I was at Wellcome for many years and some of the drugs that I was involved in developing came through and made a difference in HIV, in particular, so it’s good to see that happen. On a personal basis, I was very happy when two collaborative pieces of research I did when I was at Wellcome and latterly GlaxoWellcome came out in Nature journals, so that was really good.[Citation4,Citation5] That’s the bit I like best and is a great way of getting recognition from peers.
Disclaimer
The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Expert Reviews Ltd.
Financial & competing interests disclosure
The interviewee is affiliated with Integrated Medicines Ltd (Cambridge, UK), a strategic consultancy in precision medicines and companion diagnostics. The interviewee has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Additional information
Notes on contributors
Eddie Blair
References
- Review on Antimicrobial Resistance. Rapid diagnostics: stopping unnecessary use of antibiotics. Oct 2015. Available from: www.amr-review.org.
- Blair ED, Stratton EK, Kaufmann M. The economic value of companion diagnostics and stratified medicines. Expert Rev Mol Diagn. 2012;12(8):791–794.
- Centers for Medicare & Medicaid Services. Accountable Care Organizations. Available from: www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/ACO/index.html.
- Pizzato M, Blair ED, Fling M, et al. Evidence for nonspecific adsorption of targeted retrovirus vector particles to cells. Gene Ther. 2001;8(7):1088–1096.
- Bartlett NW, Walton RP, Edwards MR, et al. Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation. Nat Med. 2008;14:199–204.