Category Archives: Features

Book review: ICR Guide to Freelancing (4th edition)

The ICR Guide to Freelancing (4th edition)

By Helen Glenny PhD HonFICR CSci & Allan Esler Smith BSc FCA

£17.50 (+ £2 p&p) ordered direct from The Institute of Clinical Research

 

Over the past few years, working freelance in clinical research has become far more prevalent. It’s unclear to what extent this is due to professionals taking greater control over their careers, choice of project and work/life balance, or whether the trend towards workforce flexibility, which has already pushed personnel from pharma companies to CROs and “functional service provider” employment agencies, is continuing to push down to its logical conclusion: the individual employee. Whatever is driving this trend, more people are working in clinical research as freelance consultants and contractors than ever before, and many more are either considering it or worrying about it being forced upon them.

This timely new edition will give many people food for thought as they decide whether working freelance is a sensible career move for them, and a wealth of information and advice if they decide to take the leap. It provides a realistic view of why freelance life might be the best move someone ever makes, but also the many ways it might all come crashing down if not managed carefully.

The book builds upon three previous editions published since 2004, and continues ICR’s mission of providing valuable information and advice to clinical research professionals. Chapters deal with developing a coherent and usable business plan, explores common ways that businesses fail, discusses legal and commercial responsibilities, and business development and marketing, along with the practicalities of working without the technical, administrative, intellectual or emotional support of a larger organisation. The book includes “case study” interviews with four freelance clinical research managers, who discuss the benefits and challenges of their chosen career path. In my opinion, though, the most useful section of the book is a 30-point checklist, which brings together the key tasks discussed throughout the book in an easily-actioned format.

Sections of the book that deal with legal and tax matters refer specifically to the UK, and have been updated by a Chartered Accountant who has worked with thousands of freelancers and small businesses, but similar principles may apply in other countries, and anyone considering this career move should take individual professional advice in any event.

This is a very interesting book, which will be of great value to anyone planning to make 2014 the year when they take a leap in their career.

Click here to visit the ICR website and order your copy of this book.

“Sympathy for the Devil” – Book review

Here is my review of “Sympathy for the Devil” by Gary Acton MD, as published in the September 2013 issue of Clinical Research focus. If you are interested in reading the book, click here to order it via Amazon.

Clinical research is a tough area to work in. I’m sure most people reading this piece know how it feels to work on a study that under-performs or even fails. But what if that under-performance caused the drug’s development to be terminated? Or led to the failure of the whole company? This raises the stakes. Magnify that by the fact of working in a relatively small biotech company, and then by choosing to work almost entirely in niche areas of oncology, and you’ll get an idea of the pressure experienced by people like Gary Acton and described in this excellent book.

This is a true story. It follows the rise and fall of Antisoma, a company that worked with monoclonal antibodies and other classes of novel compound to develop treatments for conditions including Acute Myeloid Leukaemia and Chronic Lymphocytic Leukaemia. Those of you who follow news around the biopharma sector will know that Antisoma failed in 2011, after pivotal trials of both its flagship drugs were terminated. Through a quirk of the corporate world, Antisoma still exists as an entity, but is now nothing more than a vehicle for investing in other businesses, not necessarily even in the biomedical sector. Gary was Antisoma’s Chief Medical Officer, taking a leading in designing the company’s development portfolio.

The book is as much about business as it is about medical science and regulatory affairs. While the science is certainly at centre stage, significant sections of the narrative deal with the challenges around determining whether the market value and potential price-point of a treatment makes it viable to invest in its development. Even more significantly, a constant concern is securing investment to provide the cashflow that any small company to find out whether their drug will make it to market at all. This aspect of the story is as thrilling as the science, and echoes other books I’ve read on companies living through the dot-com boom and bust.

Of course, there is plenty of science in this book too, with plenty of detail about specific classes of tumour and the approaches taken to combat them. As someone without a specific background in oncology, I felt that I learned a great deal from reading this book, but it certainly didn’t feel like a textbook. Gary also puts the inner workings of the FDA and EMA committees under the spotlight, and he makes a strong case for reform to the regulatory systems, particularly around treatments for rare forms of cancer. I hope to explore these views with Gary in a future interview.

Although it is a weighty book (physically and conceptually) it is also very readable, and has a clear narrative line focusing on the people involved. As a reader, you become involved with the struggles faced by the Antisoma senior management team, and Gary’s pen-portraits of other key figures in the story, and characters throughout the oncology community, are vivid and engaging. But more gripping by far are the descriptions of individual patients, whose courage in the face of (often terminal) illness is inspiring.

Although the story is ultimately one of a company’s failure, it highlights the passion throughout the clinical research community to make a difference to the lives of patients, and the resilience to take a hit, stand up and keep fighting. If anyone needs to be reminded why they first got involved with drug develop will find it here.

Discussion on insights into hepatitis C research

A few days ago, I appeared as a panellist on a webinar discussing the results of a recent survey on patient awareness of clinical trials within the hepatitis C patient community, hosted by Tudor-Reilly. We discussed how to raise awareness of HepC clinical trials, some of the issues around conducting studies in this therapeutic area, and how these findings might be applied to patient engagement in clinical research more generally.

The webinar was led by Peter Coe, Chairman of Tudor-Reilly, and the other panellists were:

  • Dr Matthew Foxton, consultant hepatologist
  • Andrew Langford, CEO of the British Liver Trust
  • Karen Donovan, principal of healthcare consultants Health Business Group

The audio and slides from the webinar are now available [here].

Speaking at a webinar on the “Internet-enabled” patient

I will be speaking later today in a live webinar hosted by Tudor-Reilly. Here is their invitation to the event, but I also hope to be able to link to an audio recording in a few weeks’ time.

We are hosting a live webcast on Thursday, 18 July to discuss the findings of Tudor Reilly Health’s new white paper Doctor disconnect. Our research has shown that the internet now rivals healthcare professionals as a source of information about clinical research and that, in the majority of cases, doctors are not initiating conversations about clinical trials with their patients.

Join our webcast from 4-5pm GMT to hear a panel of leading voices including Andrew Langford – chief executive, British Liver Trust, Dr Matthew Foxton – consultant hepatologist, and Andrew Smith – independent commentator, discussing what the findings mean for patients and carers.

Copies of the white paper will be available to download shortly before the event.

If you would like to join the webcast, send a request to neil.hardman@tudor-reilly.com.

Summer reading list: New books on oncology, transforming medical research & the lighter side of molecular biology

Over the coming weeks, we will be publishing several book reviews on ClinDev. Here are some of the books we’ve received so far:

  • Sympathy for the Devil: The Definitive True Story of Cancer Biotechnology and Its Battle Against Disease, Death and Destruction (Gary Acton, Matador, RRP £18.99). The publisher describes this as a unique insight into the chaotically unpredictable world of cancer medicine and the biotechnology industry, the account of one company struggling to survive, as all their experimental cancer drugs fail, revealing, for the first time, the extraordinary world inhabited by the people involved in cancer drug development.
  • Medical Science in the 21st Century: Sunset or New Dawn? (Desmond J Sheridan, Imperial College Press, RRP £38.00) The publisher describes this book as describing the 30-year decline in the productivity of medical research in the context of its stunning past successes. The book deals with the creative nature of original science and presents a vision of what medical science can deliver during the coming half century and what is needed to overcome the present challenges.
  • Alice’s Adventures in Molecular Biology (Arieh & Roberta Ben-Naim, World Scientific Publishing Co Pte Ltd, RRP £18.00) The publishes states that there is no other book of this kind that discusses the fundamentals of molecular biology in a lighter fashion. In this book, scientific facts are melded with fiction and the account is imbibed with humor.

Sarah Rickard discusses the NHS R&D Forum conference

Here is an interview I recorded with Sarah Rickard, at the end of this year’s NHS R&D Forum annual conference.

We reflect on two days of lively and positive discussion on how to manage clinical trials within the NHS, and some of the key themes that were brought out through the conference.

Risk, Metrics & Reputation: Partnerships 2012 Conference Report Part 2

This report was originally written for Clinical Research Focus magazine, but wasn’t published when it was fresh. I’ve published here to add it to my personal archives…

The 2012 “Partnerships in Clinical Trials” conference in Hamburg attracted around 700 delegates and nearly 100 exhibitors to discuss the challenges and opportunities in working with commercial partners throughout clinical development. The first part of this report, published previously, presented some of my personal highlights from the conference’s plenary sessions. This article will focus on a variety of the topics discussed in the parallel sessions.

Risk-based monitoring

One of the most widely-discussed topics around clinical operations at the moment is risk-based monitoring (RBM). Following guidance from both the FDA and EMA in 2011 years, most companies are considering how to adapt their oversight to be more proportionate to the specific risks (to participants and to data quality) of the project. A show of hands at the start of this session demonstrated that roughly half the delegates in the room were actively piloting RBM within their organisations. According to the session chairman, Dr Elspeth Carnan, Executive Director and Head of Global Clinical Site Management at Amgen, many companies are interested, but are struggling with precisely what to do. There is little clear evidence of widespread adoption of fully risk-based monitoring solutions.

The basic model for RBM is to develop criteria to reduce the amount of source document verification (SDV) that is conducted, targeting sites where there is least certainty for good quality. This reduction in active site-based monitoring is accompanied by automated remote monitoring using EDC systems, with triggers in the centralised analysis in place to prompt site visits in specific circumstances. This increased use of centralised monitoring offers the potential to maintain excellent data quality and speed while reducing the resource burden. This could result in a reduced requirement for monitors, or enable them to focus their attention on training and motivation for sites that need more help. Elspeth confirmed that Amgen are currently in a pilot phase with RBM, and in addition to a reduction in the time and cost associated with site visits, the increased use of real-time data enables better medical monitoring of the overall study.

Geoff Taylor, Director of Clinical Quality Assurance at Eisai, commented on the threshold at which RBM becomes possible; before starting to reduce on-site monitoring, it’s necessary for have confidence in the quality of a site’s performance. This should be automated, and ideally built into the CTMS, comparing performance and quality metrics with pre-defined rules across the study. He also highlighted the shift of attitude required to move to RBM: in the past, we have existed within a “cocoon” of direct regulation, where companies are told precisely what to do. The current guidelines “rip up” this mindset, replacing it with a position where, “as long as you have good, supportable data, how you do it is up to you”. This is a position I’ve heard, particularly from leadership at the FDA, on many issues over the past few years; the real test, though, will be how inspectors react to this new way of working, and indeed the response to any instance where a significant issue is missed despite an appropriate RBM plan having been applied rigorously. Concerns of this type may be partly responsible for so many companies still being at a pilot phase…

Klaus Beinhauer, Senior Director and Regional Head of Monitoring & Site Management for Bayer, identified some key criteria for making RBM work. It is important to develop robust reports, but it is even more important to have clarity over hand-off points between clinical and data management teams. Change management is important, particularly for CRAs who have spent their entire careers conducting 100% SDV. Another important issue is how much more agile companies will need to be in allocating monitoring resource: as data changes, the peaks and troughs of resource requirement will increase in magnitude, and the balance of sites and studies requiring on-site monitoring will shift. Managers will need to think very carefully about how they will handle this.

Implementing RBM for CROs

In a second session, Ben Dudley, Executive Director of Alliance Management for Covance, gave a more practical talk on how to implement RBM into clinical development partnerships. He reiterated that risk-based monitoring is not simply reducing SDV across the board, nor is it treating all sites and all studies in the same way: it is essential to identify and address the key risk points that have the greatest potential to impact on patient safety and data quality. This risk-adaptation must be dynamic, data-driven and iterative, and future product approvals may depend on demonstrating that these risks have been identified and adequately addressed.

Ben highlighted that different sponsors may have different drivers to ask for RBM: one sponsor might be trying to achieve cost savings and assume that there will be no change in quality, while another might be looking to focus on data quality to align with regulators’ expectations and assume that there would be no overall change in cost. It’s important for CROs to identify the drivers and to adapt the RBM model used accordingly. However, it is also essential to do this within the context of standardised company processes and objective evaluations to ensure that risk avoidance and mitigation are robust in either scenario.

As is always the case in these sorts of relationships, Ben advised sponsors to engage early to discuss their thinking around RBM with their CRO partners, to keep the enhanced risk assessment off the critical path for the study and to leverage the CRO’s experience in implementing RBM for other clients. He suggested that by pre-defining the process and governance arrangements, the strategic and tactical activities can be separated, so that sponsors can use a more efficient “trust but verify” model of oversight during the study.

Metrics & insights

It is a truth universally acknowledged that clinical development is becoming more expensive, with pressure to do more with less. The reason generally given for this is that studies are becoming more complex and clinical trial timelines are increasing, with patient recruitment generally considered the main reason trials fail to complete on time. However, in a presentation tucked-away in a mid-afternoon slot, Christine Blazynski, Chief Science Officer for Citeline turned this hypothesis on its head!

Citeline has a number of proprietary data products tracking various performance metrics across the clinical trial sector, drawing data from over 20,000 public domain sources (including publications and registries but also press releases and company reports). Christine used these to assess trends in trial duration across a number of disease areas. Her team examined completed, industry-sponsored phase 2 and phase 3 clinical trials that had started from 1999 to 2010. The study looked at trials with variable study periods based on endpoint-driven protocols (eg, oncology and cardiovascular studies) but also at trials with defined study periods (eg, for chronic conditions such as RA, asthma and diabetes).

She presented data for a series of therapy areas, including breast cancer, rheumatoid arthritis and HCV, and demonstrated that in all cases, average trial duration has actually decreased. In all but a handful of cases, patient enrolment time has also trended downwards. This has huge implications for the ‘received wisdom’ across the industry, and also brings into question the true cause of the spiralling cost of R&D. She suggested that possible reasons could include the investment in local infrastructure and intelligence to underpin the globalisation of research, while more complex studies might also involve more procedures, more samples and higher associated transport and analysis costs (particularly, again, when working in unfamiliar countries).

Continuing her presentation, Christine looked to dig a little deeper into reasons behind this downward trend. Here, the story was less consistent, varying by therapeutic area. For phase 3 studies in RA, it appeared that studies were simply being conducted more efficiently: enrolment time and study time had both decreased, as had the number of countries and sites used. (The total number of patients accrued was not reported, so it’s possible that studies were simply designed to be smaller.) In HCV, breast cancer and type 2 diabetes, enrolment and study periods had also decreased, but there was a marked increase in the number of countries used and, for HCV, a doubling in the average number of sites.

She ended her presentation with some questions to stimulate further research. What are the forces driving these trends around geography; will the geographical breadth of studies keep expanding or (as some industry leaders are suggesting) has the trend towards globalisation already peaked? What are the implications of recruiting more specific patient groups (eg, genetic/ethnic populations, elderly or paediatric patients etc.) And most crucially for this audience, which companies are most effective in driving trials forward?

Standardised performance metrics

The following presentation also looked at performance metrics, albeit from a different perspective: developing and using the right ones! Guy Mascaro is President of the Metrics Champion Consortium (www.metricschampion.org), a not-for-profit organisation comprising nearly 100 pharma companies, CROs and universities, with the aim of improving the clinical development process through the use of standardised performance metrics around cost, time and quality. Guy started his presentation by reminding us that metrics are not weapons to inflict on others, but they can play an important role in influencing behaviour in sponsors, CROs and sites. This integrated view is vital, as misaligned performance metrics (or, worse still, performance metrics that folk think are aligned but are actually subtly different) can create challenges and undermine the very performance they are intended to improve!

Metrics can be developed around speed (ie, timeliness and cycle time metrics), cost/efficiency and quality. Guy explained that it is vital to focus on all of these equally, as over-reliance on metrics of one type can detract from performance in other aspects. To encourage this integrated approach, Key Performance Indicators (KPIs) and Key Quality Indicators (KQIs) can be be integrated into a single metric. For example, if you have a KPI of “approve protocol on time”, it can be integrated with a KQI of “protocol quality score” to give a combined metric of “approve high quality (quality >x%) protocol on time”.

The MCC has developed sets of performance metrics in several areas, with the clinical trial performance metrics being published in 2010. Each metric is rigorously defined, including measurement unit, target range, reporting frequency etc. and organisations are encouraged to use the same definitions to ensure that inter- and intra-company reporting is unambiguous. The set of clinical trial performance metrics include 52 individual metrics (from “protocol quality tool” to “study drug-related SAEs reported per dosed subject”) and four exploratory metrics. These are presented on a process map for the entire study, showing where in the study the metric becomes relevant and which other metrics are related.

Combinations of metrics can be used to develop scoring tools, for example to inform site selection within or between countries. These tools can be used strictly as the basis for decisions, or can be used more subtly to inform choices and suggest when to mitigate risk. For example, if a site scores poorly in the selection tool but involves a Key Opinion Leader, the decision might be made to retain the site in the study but to plan specific risk mitigation activities. While this is perhaps little different from how these issues were handled in years gone by, the use of the scoring tool has documented the risk in advance and triggered a documented decision on how to proceed, both very important activities under the new risk-adaptive mindset (as discussed above).

Going beyond philanthropy

The final presentation to be covered in this report looks at the pharmaceutical industry from a very different angle. At his keynote speech at the 2012 ICR Annual Conference, David Gillen drew our attention to the Access to Medicines Index (www.accesstomedicineindex.org), which ranks pharma companies on various aspects of corporate social responsibility, going beyond philanthropy to take account of patents, pricing and public policy and more on the developing world. The report was first compiled in 2008, then in 2010 and the 2012 report was published a few weeks after this presentation. The driving force behind the project, Wim Leereveld, spoke to a packed conference room, discussing the thinking behind the project and its increasing impact on pharma’s reputation.

The goal of the project is for pharma companies to learn from their peers to improve practice around access to medicines. It also plays to the natural competitiveness of corporate CEOs: if a company comes in at #15 in any ranking, a typical CEO will want to improve on that position next time!

The report was developed with the full cooperation of the stakeholder companies: representatives came together to discuss and refine the criteria to be used, and their relative importance, so that all the companies could ‘buy in’ to the project’s transparency and agreed that the independent assessment and ranking was valid. Activities and impact were measured across 103 countries, based on World Bank and United Nations classifications around low-middle income and medium human development. The 2010 report was ranked #5 in a “rate the rater’s” ranking for credibility of methodology and results, and was described as “a very important project” by the Director-General of the World Health Organisation, Dr Margaret Chan.

In 2008 and 2010, GSK topped the list, with Merck, Novartis and Sanofi-Aventis also in the top five in both reports, with Novo Nordisk and Gilead both also scoring well. Each individual company report is broken down across the different types of criteria, so we can see that one company scores well for patenting while another performs better on philanthropy. For 2012, the weighting of the categories was changed again, with emphasis shifting from commitments to performance, and from R&D to equitable pricing and distribution. Of course, he could not discuss the actual results prior to publication.

Interestingly, for a report that many of us had assumed to be directed at clarifying pharma’s reputation with the general public, Wim explained that the prime target of the report is actually the investor community. He displayed the logos of 30 leading investment companies who support and take notice of the report, and who manage combined assets of $3.7 trillion. This emphasis is pragmatic, as their support of the pharma companies forces businesses to take notice on a financial level rather than on a purely social and reputational level that could be over-ruled by investors’ drive for increase return on investment (ROI). In the Q&A session after his presentation, I asked about the impact on pharma’s reputation with the general public. Wim replied that the public is a much more diverse audience, and more difficult to reach, and that assistance on getting the message out more widely would be appreciated.

The 2012 report was published a few weeks after this conference. We plan to bring you an analysis of the new report and an exclusive interview with Wim in a future issue of CRfocus.

From Outsourcing to Integrated Alliances: Partnerships 2012 Conference Report Part 1

This report was originally written for Clinical Research Focus magazine, but remained unpublished while it was fresh. I’ve published it here to add it to my personal archives…

For over a decade, the “Partnerships in Clinical Trials” brand has been at the forefront of commercial conferences for the clinical research sector, focusing on issues around selection and use of CROs to conduct clinical trials. The event takes place in the USA, Europe and Asia/Pacific each year, and the 2012 conference took place in Hamburg last November. The conference attracted around 700 delegates and nearly 100 exhibitors to discuss the challenges and opportunities in working with commercial partners throughout clinical development.

This report presents of some of my personal highlights from the plenary sessions of the conference. A second article will focus on topics discussed in the parallel sessions.

Collaboration to drive innovation

I arrived mid-way through the opening plenary session, to see Emiliano Rial Verde of McKinsey speak about “Collaboration as a lever to drive innovation and productivity of clinical operations”. He commented that R&D spending in the pharmaceutical industry is typically receiving an internal rate of return (IRR) of 5-7%. While this might be an acceptable figure at the moment, he suggested that when the wider economy recovers, investors would be looking for substantially better returns and may look to other industries. However, he projected that in order to reach an IRR of 11-15% the industry would need to achieve the same output while spending as much as 50% less!

However, he cautioned against focusing too heavily on cost reduction rather than the potential to create additional value by collaborating better. Drawing on examples from the oil and movie industries, he suggested that networks of companies working together in more open, trusting relationships would be a good way to achieve this, and the complexity and high, increasing cost of the clinical operations sector make this an ideal space in which to explore this new way of working. Emiliano described a “ladder” of types of working relationship, from fixed unit costs through to full risk-sharing, but criticised many companies for simply looking to innovate around a single “rung”.

For a real long-term partnership, Emiliano said that both parties really need to commit to making it work, with more flexibility around working practices and an openness to learn from each other. The oversight process, in particular, should be re-invented to reduce the large pharma management overhead still in place for many trials conducted by CROs. Pharma should learn to let go a little and “be a good co-pilot”. In return, CROs should be prepared to trade-off some of their short term profit to earn longer-term trust, by increasing transparency over their own costs and productivity.

Conductors as leaders

In the final segment of the first plenary session, Itay Talgam of the Tel-Aviv Symphony Orchestra use examples from great orchestral conductors to inform leadership styles in business. He contrasted the “micro-management” of Riccardo Mutti with the welcoming vagueness of Herbert von Karajan before highlighting on the style of Carlos Kleiber, who has been routinely described as one of the conductors most admired by other conductors. His style centred on instilling a sense of the “emotional purpose” of the music in his orchestra and providing space for individuals to add their personal contributions, without losing control or ignoring details. While some “inspirational speakers” simply provide an interesting diversion to energise the audience, Talgam gave us some genuine tips on how we can become more effective leading our teams, from a perspective that many found more engaging than a simple “soft skills” course.

State of the CRO market

Michael Martorelli (Fairmount Partners) and Tim Wilcock (Leader Partners Ltd) both gave perspectives on the pharma outsourcing market from the financial sector. Michael contrasted the contract manufacturing sector, where M&A activity is high, with much lower levels of activity in clinical, where companies like Clinipace, Quintiles and Wuxi have been some of the most active. Quintiles were highlighted as having made five acquisitions in 2012, and he alluded to rumours of an IPO. Other noteworthy transactions included Piramel Healthcare’s acquisition of Decision Resources Group, Aligent Technologies buying Dako and particularly inVentiv, who recently added Pharmanet/i3 and Campbell Alliance to their portfolio of pharma marketing, communications and sales service companies.

The number of less familiar names on this list confirms Michael’s point about new players entering the sector, with a blending of clinical research and healthcare provision mirroring some of the ideas around pharma’s own evolution. Companies are expanding to avoid price-constrained segments and making “tuck-in” deals to get more business from existing customers.

Suggesting the sorts of companies who might be next to be acquired, Michael mentioned well-regarded providers of specialised services or operating in specific geographies, along with informatics companies, who are seen as being able to “close the loop” from treatment, through research to improved treatment. He also advised us to watch for some of the private equity firms that have entered the sector over the past few years looking to make an exit.

Looking forward, Michael sees more of the same:

  • More tuck-in deals
  • More M&As to expand into new geographies and specialist sectors
  • More non-traditional buyers
  • More combinations of research companies with healthcare provision companies

Tim Wilcock highlighted the “macroeconomic noise” confounding any analysis of this sector, from the US “fiscal time-bomb” to “basket-case” EU economies and slowing growth in the BRIC countries, all of which are increasing irrationality and volatility among investors. As a result, caution abounds, with companies hoarding cash and private equity investors struggling to find enough opportunities to invest.

Tim reported that the total pharma R&D spend was $135b in 2011 and projected to grow at 1.5% for the next few years. Of this, roughly $94b was spent on development, and $26b of that was outsourced. Nearly half of this development spending ($44b) is on Phase 2/3, and Tim estimated that roughly $11b of that is outsourced. Next he presented a chart of the leading CROs in the outsourced clinical research market, but with the caveat that many of these companies don’t publish financials, so outside the top five the figures may be less accurate. Overall, Tim predicted that the market would grow at 8.5% CAGR, reaching $41b by 2017.

Providing a counterpoint to what Michael had said earlier, Tim suggested that there would be some high profile transactions among the top-tier CROs in the coming year. He cited “informed sources” talking about a lot of background activity around a number of companies, and reiterated the rumour of a public flotation for Quintiles.

By contrast, the mid-segment of the CRO sector is ripe for consolidation, if only to maintain access to a client base that is also shifting. Small CROs could also attractive candidates for acquisition, particularly if they can provide specialist expertise to mid- or large-sized CROs looking to boost their own services.

Tim concluded his presentation by saying that unless you’re looking to buy into the top-tier, there are market opportunities around, and that there is plenty of scope for high quality organisations to outperform the (already relatively positive) growth predictions for the sector.

Profound changes in the outsourcing landscape

One of the highlights of any conference looking at the “big picture” of drug development is a plenary presentation from industry visionary and Centerwatch founder Ken Getz of the TuftsCenter for the Study of Drug Development. He started this presentation by highlighting the global economic downturn as a key point in driving strategic outsourcing, and pointed to a four-fold growth in the number of outsourcing companies between 2000 and 2010, and to the fact that since 2010 CROs have employed more R&D staff than the pharma companies they serve. The CRO sector is also growing faster than R&D in general, showing 13% growth compared with only 7% growth in pharma R&D spending.

By his analysis, the outsourcing landscape is 5x bigger than suggested by other analysts! This corresponds to 45-50% of total R&D spending, which is much higher than is commonly believed. This takes account of the full scope of outsourced activities, from applied research through non-clinical and clinical research to formulation and manufacturing, with consultancy, business development, distribution and related service areas along the way. His group calculated the 2011 global market size for all outsourced R&D to be $115b, with only 15% of this being clinical research.

There are distinct differences in the extent to which companies are outsourcing different types of activity, and what outsourcing models are used. Activities like study design and regulatory strategy are typically (80-85%) kept in-house with any outsourcing limited to specialist consultancies. Conversely, site selection, start-up and enrolment are mostly (70-80%) outsourced, with a mixture of alliances, functional service provider (FSP) and full outsourcing being used. However, the market is fragmented, with relatively few companies active in all of these sectors. Even when companies are outsourcing in all of these segments, it is rare to have the same preferred provider across functions.

There is scope for increased strategic partnerships or even consolidation between CROs, with a likely goal of offering a “soup to nuts” R&D service. He pointed to companies like Jubilant and Wuxi that are already well on the way to offering this in their local regions. According to a 2011 Centerwatch study, the 15 largest CROs do nearly 70% of their business using FSP or integrated alliance models, while smaller CROs do nearly 60% of their business as transactional service provision.

Ken proposed that only the large CROs can support integrated alliances, because of the investment required to support customised activities while also meeting pharma’s expectation of cost savings. These cost savings can be significant: in 2010 Pfizer consolidated 150 providers to just 17 and saved $20m, while in 2011 Lilly reduced costs by 20% and improved monthly patient enrolment volume by 93% by moving their monitoring and data management to a FSP model. Parexel also reported that FSP had enabled clients to reduce their management overhead by 60% compared with transactional services.

However, all is not rosy in the outsourced world. Ken presented data from the Avoca group, which showed that 22% of sponsors have terminated integrated alliances, with 16% reporting no cost savings and 17% seeing no reduction in cycle times.

Presenting an outlook for the next few years, Ken suggested that the major CROs will face higher fixed costs and declining margins. They will need to expand into higher margin service areas, or consider divesting divisions. They will need to increase control over their performance and efficiency, with significant investment required to provide innovative solutions. He highlighted eClinical, site performance and patient recruitment/retention as areas where several of the major CROs have already invested in platforms, such as ICON’s Iconik technology, Quintiles’ Prime Sites programme and PPD’s PatientView. Ken stated that more rapid adoption of technology is vital, as is the drive to reduce operating complexity, perhaps even by reducing the number of countries in which they operate.

Medium-sized CROs will be squeezed by a more competitive market for transactional services, and will need to make innovative partnerships with specialist providers or face consolidation as companies try to scale-up to reach the top tier.

Small CROs will tend to stay in the transactional mode but will be faced by a need to distinguish themselves as providers of specialist services. While they will work with smaller sponsors who may be unable to form integrated alliances with top-tier CROs, they will also rely increasingly on subcontracted relationships with larger CROs.

Ken closed his presentation with a glimpse of a new model for research, and a new opportunity for the CRO sector. Patient groups, particularly in the USA, are becoming more empowered and active to drive the research agenda, sponsoring research, designing studies, collecting medical information and using social media to raise awareness. For example, the Cystic Fibrosis Foundation Therapeutics has put $400m into research, while the National Multiple Sclerosis Society has provided $760m in funding.

10 years of transition

Taking a much broader look at the future of healthcare, Robert Lasser of PharmaNet/i3 spoke about how the current R&D model needs to change over the next 10 years. He highlighted that chronic disease is soaring, particularly in the developing world, and that the imbalance of treatment over prevention is not sustainable. However, in contrast, economic factors mean that policy-makers are setting more rules and looking to link payment more closely with performance, which continues to prioritise treatment over prevention. In addition, the boundaries within healthcare are blurring, with delivery of care becoming less separable from the treatment itself.

Global demographics plays a huge part of this. By 2022, there will be an additional 1b people needing healthcare, and 10% of the global population will be 65 or older. Polypharmacy is already a huge issue in the older population, with 40% routinely taking four or more medicines. More people living longer and continuing to be treated for chronic illness will place a huge burden on healthcare systems. In addition, people in developing countries are increasingly developing “western” conditions such as hypertension and diabetes. This represents a huge threat for healthcare payers, but also a huge opportunity for prevention to make huge savings: preventing 10% of diabetes cases could save India $3b (or even more if the cost of treatment gets closer to US levels).

Robert spoke about the changing face of healthcare delivery, with more complex diagnostics and even minor surgical procedures being conducted in primary care, and greater emphasis on web-based self-diagnosis and over-the-counter drugs for chronic conditions. This will make adherence to treatment more of a challenge, with healthcare providers needing to understand the behavioural disconnect that reduces the value of interventions.

He presented the current situation as a set of value chains, with pharma companies, healthcare providers and payers currently having relatively few shared motivations and metrics. Robert proposed a model where these value chains are much better aligned, linking risk-based steps for regulatory approval with electronic patient health records to track and report on disease management, and to inform payment policies. Outcomes data could be used to highlight patient risk factors and underpin the role of prevention, while the communication and brand management skills of pharma companies could also be used to better inform patients and increase adherence. This would result in a disease management package that be able to combine branded and generic medicines along with health analytics and involvement with research.

Robert went on to discuss the “live licensing” model proposed by PriceWaterhouseCoopers, in which an automated dataflow permits rapid access to the market with a limited license around Phase 2a, with data from all clinical use being collected and centralised to support extension to the license as better evidence is developed. This alters the traditional cost/revenue curve for a medicine, reducing time to market and initial costs, bringing forward the break-even point, and giving greater flexibility to capture value throughout the lifetime of a product.

In the final segment of his presentation, Robert discussed the different models for pharma/CRO collaboration, from preferred vendor status through alliances to full joint ventures. These more strategic, collaborative ways of working provide greater scope for value creation, but are more difficult relationships to create and maintain. To make them work, sponsors and service providers need to recognise the trade-offs they each need to make, adjusting their risk profile around staffing, pricing and the success of the product. He suggested that one way to make this work could be the creation of joint executive committee between sponsors and providers, to build and document the relationship beyond individual studies or products, to provide a pathway to resolve any issues that might arise, and to enable perceptions on both sides to equilibrate.

Putting patients at the heart of the trial

The final plenary presentation of the conference came from a man who has become known as “ePatient Dave”. Diagnosed in 2007 with renal cell carcinoma and given a median survival time of just 24 weeks, high-tech marketeer Dave deBronkart responded by seeking online resources to inform his treatment. Following surgery and participation in a HDIL-2 clinical trial, he has made a full recovery, and began blogging about the experience shortly afterwards. This prolific and engaging blog made him a leading light of the “e-Patient movement”, which highlights the power of patient engagement and enablement.

His powerful presentation (based on his very popular TED talk, available at http://on.ted.com/Dave) could be summed up as a call for industry to “let patients help heal healthcare”. Along with describing his own journey and some of the incredible people who contributed to his success, Dave called for greater emphasis on patient-centred outcomes, which are more closely related to the issues that patients themselves consider important. When viewed in these terms, specific side effects might be more tolerable, for example, if a treatment also preserves a key aspect of a patient’s independence. Similarly, to a patient with a progressive disease, Dave reminded us, time is everything, outweighing even certainty of a treatment effect if there is nothing else available. However, issues from study design to publication timelines increase delays until a treatment might be available. He also made a call for greater use of patient information to be used to underpin

Both educational and inspiring, Dave’s presentation gave a very different perspective to the day, and reminded everyone in the room that patients are the most underused resource in the whole of healthcare.

Value at Risk? 2012 FT Global Pharma & Biotech Conference

This report was originally written for Clinical Research Focus magazine, but remained unpublished so I’ve rescued it from the archives…

People like us, who work in clinical development, are used to being buffeted by changes in regulation, health service R&D policy and company tactics. But, above all that, pharmaceutical companies and healthcare payers/providers are pursuing long-term strategies that will have an impact on how we work. For over a decade, the FT Global Pharmaceutical and Biotechnology Conference has been a key event in sharing and shaping pharma companies’ strategies, with industry leaders at the very highest level coming together with investors and policymakers to discuss the topics that will shape our entire sector for the next few years.

This year, the title of the event was “Value at Risk?” This reflected the general challenge facing the sector to improve productivity and value creation as the global economy recovers: the current 5-7% return on R&D investment may be acceptable during a recession, but as the economy recovers investors may look to other sectors for returns above 10%. However, the title also reflects a more specific challenge around the move towards value-based pricing in the UK and other countries. With a more direct link between price and patient value, companies will need to find new ways to demonstrate value, and the standards by which value will be measured may also change. These were the sorts of topics that drew around 150 delegates, from pharma company Presidents and CEOs down to lowly journalists! I was pleased to represent ICR at this meeting, and present this brief report of some of the highlights of the conference.

In a change from the traditional format, much of this conference took the form of conversations or panel discussions, with very few structured presentations. Although some long-standing delegates were less comfortable with this format, it did enable the speakers to be more flexible and base their comments on the directions taken by other speakers. The first day was chaired by Andrew Jack, Pharmaceutical Correspondent for the Financial Times, while the second day was chaired by Reynold Mooney, Global Leader in Life Sciences and Healthcare at event sponsor Deloitte Touche Tohmatsu.

Value-based pricing

The first session of the meeting looked specifically at value-based pricing. Giles Denham of the Department of Health explained that VBP will come into force in some form in 2014. The details of the arrangement are still being negotiated between DH and the ABPI, but many drugs that are already on the market will be unaffected, continuing to be sold under the next ‘generation’ of the Pharmaceutical Pricing Regulation Scheme (PPRS). This has delivered stable pricing since 2010, when the Labour government changed it unilaterally to reduce NHS drug spending. Giles confirmed that NICE would continue to have a role in assessing the value of medicines, with VBP operating in a framework around NICE activities. From April 2013, NICE will also be able to include social value in its assessments, enabling consideration of a wider range of indirect costs and benefits, such as returning to work earlier or requiring less long-term care by treating symptoms more quickly. Precisely how the resulting value will be transformed into a price to be paid by the NHS is still being negotiated, but Giles stated that the intention was to use the evidence available and not require any new types of data from industry.

Giving a different perspective, the next speaker was Niklas Hedberg, Department Head for New Submissions at the TLV, the Swedish body closest to NICE in its remit. He explained that Sweden has had VBP for around 10 years. While their evaluation model was based on the early activities of NICE, but they also have the scope to use societal value, and to set the end price for medicines. Having made over 500 pricing decisions over the past decade, the TLV is generally considered to be a success. Niklas highlighted that the TLV is looking to learn more about how to value innovation (as distinct from simple improvements in treatment effect). Another area that is currently being debated is the potential for the same drug to be used in different indications. As these indications might have different impacts on wellbeing, and the drug might have different treatment effects for different indications, would it be reasonable to pay a different price to use the drug in each indication? And, if so, how would this be measured and enforced? Niklas also raised the area of orphan drugs, where the rarity of conditions means that conventional VBP models break down. The TLV is still developing its evaluation models, and is currently running a public consultation on the issue of periodic reviews to consider adjusting pricing as data evolves post-launch.

Ismail Kola, President of New Medicines at UCB, pointed out that his company had a unusually positive view of value-based pricing, because of their corporate focus on first-in-class molecules and a high ‘bar’ when looking to demonstrate superiority over existing comparators. He raised the interesting issue of societal vs personal/family value and gave the example of cancer survival. On purely economic measures, adding another 3 months to the survival of a patient with terminal cancer may be hard to justify, it is extremely important to the patients and their families, leading to political pressure to pay for treatment that might be absent for less emotive or chronic treatment.

The other speaker in this session was Corinne Savill, Global Head of Pricing and Market Access at Novartis. She acknowledged the complexity around recognising value, and especially how this differs between countries. She stressed that the evaluation process shouldn’t require more time to demonstrate value, and that the current lag from listing to NICE assessment results in a delay to actual sales. Giles Denham responded that this time is currently only 4 months, and that developing better ‘teeth’ to implement NICE guidance was on their ‘to-do list’.

Coming back to Niklas Hedberg’s point about differential pricing, Corinne Savill gave the example of France, where price is calculated based on estimates of expected usage in different indications, and adjusted after follow-up. Ismail Kola said that this issue will be exacerbated as we move towards molecular diagnosis: if a general condition such as diabetes is subdivided into multiple diagnosable variants (the ‘mini-buster’ model) then it will be even harder for VBP to operate. Giles Denham responded that this might not be such a problem if the smaller subgroups responded better to treatment, with greater value per patient in the responding groups offsetting the lower value to non-responders.

Andrew Jack moved the discussion on by asking whether VBP is just a ‘cover’ for governments to enforce lower pricing. He asked whether TLV benchmark pricing against their neighbours who don’t operate VBP. Niklas Hedberg confirmed this, stating that at present pricing shortly after launch is broadly equal to neighbouring countries, but that a gap develops after a few years, as deals are done to reduce the price in other countries, while in Sweden they are fixed. To address this is the purpose of the consultation he mentioned earlier. He also challenged the ‘innovation premium’ proposed by Corinne Savill, asking whether it is worth paying more for a marginal improvement in treatment simply because it was achieved by a new mechanism.

Before this session was brought to a close, Ismail Kola again raised the issue of value to whom, highlighting the importance of patients in determining how the balance of efficacy and side effects would impact on the assessment of value. From the payers’ perspective, he stated that the timescale for realising patient value is also important. While less of an issue in the UK, health insurers in the USA (ie, the largest single group of payers) have a very short horizon in which they want to see an outcome: if it takes 2 years to deliver patient value, the patient could well be with another insurer!

Chairman’s panel

The other highlight of this conference came on the second day, when the Chairmen of five major life science companies came together to discuss governance, culture and diversity:

  • Joaquin Duato, Worldwide Chairman of Pharmaceuticals at Johnson & Johnson
  • Jorge Gallardo, Chairman of Almirall
  • Franz Humer, Chairman of the Board at Roche
  • Israel Makoc, Chairman of SUN Pharmaceutical Industries
  • Martin Valesco, Chairman of AC Immune

The session opened with some words from Franz Humer, who asked whether policymakers actually want innovative medicines, given their pressure to impose a step-change reduction in price. In contrast, the public demand for innovative drugs is enormous, and he felt that taking a patient-centric approach will deliver more value.

He called for companies to adapt now: “wait and see won’t work!” Productivity and cost-efficiency are no longer “nice to have” and must be integral to innovation. He urged companies to take a different perspective on their operating costs, from head-office down. The structure of global organisations must be simplified, and local affiliates trusted more to run their own operations with less direct linkage to HQ. Development operations need to deliver a reduction of 30-50% in per-product costs over the next 5 years. When asked how this could be achieved, he called for greater innovation in the conduct of clinical trials, and particularly in their design and their use of technology.

In order to deliver these improvements, Humer highlighted the importance of company culture in recruiting and retaining top talent. This must include giving people space to experiment and learn in all aspects of the R&D process, and even extend to allowing them to fail sometimes! He closed with an upbeat thought: that innovative pharma is not at the end of its life, it’s only at the beginning!

Joaquin Duato of J&J reflected that the modern pharmaceutical industry is barely 100 years old; and the dramatic increase in lifespan throughout the 20th century should be seen as one of its major achievements. He reiterated the importance of collaboration between organisations of every sort, highlighting that shared investment in pre-competitive research and infrastructure enables companies to diversify their activities, which is vital when operating in such a high-risk sector.

Israel Makov of SUN commented that pharma is very knowledge-rich, but this knowledge is kept in multiple silos within each organisation. It is these silo structures that are preventing the decline in R&D productivity from being addressed. He also mentioned the increasing complexity of operating in this sector, from the scientific complexity of understanding the genetics of population subgroups through the regulatory and commercial complexity of operating across new global markets, to the managerial complexity of dealing with networks of suppliers, alliance partners and other stakeholders. He called for companies to refresh and expand their management capacity to deal with this increasing complexity.

Martin Valesco of AC Immune picked up on a theme that come up several times during the conference: the trend towards integrating medicines with treatment and other care services to provide a single package that would retain the interest of payers. This could be something as simple as developing strategies to improve patient adherence, or as elaborate as developing a suite of diagnostics and therapeutics to cover entire treatment pathways. Joaquin Duato echoed this, saying that pharma companies need to become better thought leaders on the role of medicines in improving healthcare, not just reducing prices.

Franz Humer then made what was possibly the most significant statement of the conference. In his opinion, “apart from the UK, western governments are generally uninterested in the health and viability of the pharmaceutical industry. Emerging economies are keener.” He proposed that the savings made by moving patients to generic treatments as patents expire should be recycled to better fund innovation (presumably through universities and start-ups) rather than purely cutting costs.

Final thoughts

There were many other interesting points raised throughout the meeting that would take too long to report in full. In closing this report, I’d like to give a few of those final thoughts…

  • Peter Harpum of the University of Manchester suggested that we should compare ourselves with the oil/gas and military aviation industries, which have very similar cycle times, development costs and emphasis on regulation.
  • He also suggested that we look at the food industry, which deals with new product failure rates of up to 97%.
  • Moncef Slaoui, Chairman of R&D at GlaxoSmithKline called on the pharmaceutical industry to repair its entire development model, likening the current activity to “pumping air into a flat tyre”.
  • He also called for novel kinds of pre-competitive collaboration, even going so far as to suggest sharing infrastructure and validation of investigational sites.
  • Prof. Sir John Bell of Oxford University and spoke about the volume, variety and velocity of ‘big data’, calling for better incentives for NHS Trusts to code data better into electronic patient records to enable better data sharing for research.
  • Greg Rossi of AstraZeneca highlighted the potential for ‘real-world’ studies to provide insights that enable us to design better RCTs.
  • Ken Jones, President and CEO of Astellas contrasted the pharmaceutical industry’s poor reputation in Europe and North America with Japan, where it is still highly regarded.
  • Ulf Wiinberg, CEO of Lundbeck told us that depression and other mental health problems represent nearly 25% of the total disease burden in the EU and will result in $6b in lost productivity over the next 20 years. However, many major players are choosing to leave the area.
  • David-Alexandre Gros, Chief Strategy Officer at Sanofi, came out strongly in favour of transparency on clinical trial results and data.
  • Prof. Sir Michael Rawlins, who gave the closing address, said that NICE should look more closely at comorbidities, which are common in elderly populations, in addition to considering single diseases.

“Vive La Difference!” – 2012 Franco-British Symposium

The following is a conference report that was originally written in 2012 for Clinical Research focus magazine, but was left unpublished.

As a profession, we often criticise ourselves for being stuck in “silos”, whether technical, corporate or national. So, it was interesting and refreshing to represent ICR at a symposium, held in London on October 16th, 2012, that brought together nearly 50 delegates from the UK and France. The purpose of the event was to share background information and ongoing developments on a bilateral basis. While the meeting demonstrated that our two countries are facing similar challenges and responding in broadly similar ways, it was clear that there was also plenty that we could learn from each other. This report presents highlights from some of the sessions at this symposium.

Setting the scene

After being welcomed to the event by Dr Julie Maxton (Executive Director of the Royal Society) and His Excellency B. Emié, the Ambassador of France, the first part of the event gave an overview of the structures to promote and conduct clinical research in France, England, Scotland, Wales and Northern Ireland.

The French landscape

The first presentation was given by Prof. A Syrota, President and CEO of The Institut National de la Santé et de la Recherche Médicale (INSERM, www.inserm.fr). INSERM initiates around 40 studies every year, ranging from basic research, through clinical trials to public health. Around 12% of these studies are therapeutic clinical trials. These trials are run through university hospitals but also across a network of 41 Clinical Investigation Centres throughout France. In addition to 27 general centres, ten specialise in biologicals, eight in medical devices and nine in epidemiology. These centres provide a platform to support research throughout France, particularly for large late-phase and post-authorisation research. As dedicated research centres, they provide a compliant environment for the smooth set-up and conduct of both academic and commercial studies.

Prof. Syrota highlighted the Centre National de Gestion des Essais des Produits de Santé (CENGEPS, www.cengeps.fr), a set of investigator networks designed to reinforce patient recruitment to commercial clinical trials. This network was set up in 2007 as a public/private partnership and encompasses investigator networks in 21 disease areas. This suggested comparisons with the therapeutic networks set up in the UK by the NIHR, but in response to a question, Prof. Syrota clarified that the networks are less formal in structure with a smaller management overhead.

France was also the birthplace of the European Clinical Research Infrastructure Network (ECRIN, www.ecrin.org) which grew from the French national network F-CRIN (www.fcrin.org). ECRIN has hubs in all EU member states, and aims to bring together stakeholders in academic and commercial clinical trials facilitate improved competitiveness, particularly in early phase and multicentre studies.

In summary, Prof. Syrota heralded the sophisticated infrastructure and networks to support clinical research in France. However, these are underpinned by multiple financial lines and layers of administration, which leads to a fragmented system that could sometimes be co-ordinated.

Around the UK

Prof. Tom Walley next gave an overview of the history of the NIHR in England, with which many readers will be familiar. As a response to the changing parameters of their own funding reviews, universities had moved from therapeutic research to basic biomedical research, which indirectly resulted in the UK being less able to capitalise on its excellent basic research. Research was recognised as a core activity in the 2006 review of NHS R&D strategy and NIHR was founded to commission research in areas of market failure and to influence clinical practice.

While an initial priority for NIHR was to underpin practice within the NHS, he highlighted that it was important to coordinate better with groups outside the UK, to enable bigger, better studies. Tom gave the example of the IVAN study to compare Avastin with Lucentis, which was conducted with 610 UK patients. At the same time, the CATT study was making the same comparison with 1208 patients in the USA. The Persephone study on the use of Herceptin for breast cancer in the UK was very similar to the French Phare study.

Tom concluded his presentation with a mention of plans to rationalise the research networks in England. The details of this rationalisation were still being discussed, but it was likely that the 120+ networks active across England will be reduced to around 15, reducing management overhead without substantially reducing activity.

Mike Stevens, Acting Director of the Chief Scientist’s Office of Scotland, spoke next. Scotland has a system of integrated approvals for R&D and ethics, in contrast with the system in England. He said that this enables rapid approval of studies, leading to faster start-up. However, he conceded that patient recruitment to commercial studies averages only 76% of target, despite efforts to improve this.

Mike highlighted the investment of NHS Research Scotland (www.nhsresearchscotland.org.uk) in bio-repositories and health informatics. Four regional bio-repositories underpin basic research, and are based on collecting tissue using a generic, enduring consent process. In the pilot scheme, 97% of patients who were asked to donate samples in this was were happy to do so. Research into health informatics will be of more interest to CRfocus readers. The Scottish Health Informatics Programme (SHIP) aims to establish a national safe haven, firmly embedded within NHS Scotland that will provide rapid, secure access to the types of data required by clinical scientists. Due to go at the end of 2012, this will enable single electronic health records from birth to death, linkable to non-NHS data as appropriate, to underpin feasibility analyses for individual studies, inform stratification for ‘personalised medicine’ studies and facilitate epidemiological research.

Regarding working with industry, Mike reminded us that delays are not only caused by the sites and networks: last-minute changes to study protocols and other industry requirements also introduce delays. He highlighted formal collaboration as a method to increase mutual understanding and to work together more smoothly. Both PPD and Quintiles have recently signed collaborative agreements to work in Scotland.

Prof. Keith Lloyd of the Welsh National Institute for Social Care and Health Research (NISCHR, www.wales.nhs.uk/sites3/home.cfm?orgid=952) based his presentation on his group’s efforts to win research grants, as health and social care represents over 40% of the Welsh government budget. To do this, he highlighted the importance of streamlining research processes and pointed to a study turnaround of 40 days for permissions and start-up.

Prof. Bernie Hannigan of the Public Health Agency in Northern Ireland (www.publichealth.hscni.net/directorate-public-health/hsc-research-and-development) gave an overview of the situation in Northern Ireland, where much of the research is concentrated around two universities and a single medical school. She showed a series of ‘kite diagrams’ representing the distribution of research funding, demonstrating a shift towards therapeutic evaluations. She highlighted strength in respiratory/COPD research and also in new areas of research related to home-based care and stratified medicine. Bernie also highlighted an academic research partnership between Northern Ireland, the Republic of Ireland and the USA, based on US NIH peer review.

Picking up on one of the themes of the morning, she also mention their involvement in the European Connected Health Alliance (www.echalliance.com). One of the delegates welcomed these multiple projects around electronic health records, but raised the issue of interoperability, so that the datasets can actually be related. Tom Walley confirmed that there is a project to address this being funded by the Department of Health. Mike Stevens and Keith Lloyd confirmed that the Scottish and Welsh projects are discussing how to make their systems interoperable.

Regulation, governance & ethics

The second session of the day looked at issues around regulation and oversight of clinical research, generally taking a more international view.

Fergus Sweeney, Head of Patient Protection at the European Medicines Agency, gave some an update on some of the metrics collected by the EMA. At present, roughly 38% of pivotal trial data for EMA submissions has been generated within the EU, compared with 30% from the US. Given the general distribution of market share for clinical research, it might be a little surprising that US data does not dominate. However, it is perhaps less surprising that the proportion of data coming from the ‘Rest of World’ is increasing. Digging more deeply into the data, it is clear that while the number of industry clinical trials being conducted in the EU is decreasing slightly, the total number of EU patients taking part in those studies is decreasing more dramatically, suggesting that the number of sites per study and/or patients per site within the EU is declining. This is one of the driving forces behind the proposed Clinical Trials Regulation, which was published in draft form over the summer.

Fergus went on to speak about the move towards a risk-based approach that is going on in many aspects of clinical trials. He suggested that much of the resistance to change is to do with industry’s perception of regulators’ requirements rather than the reality. He clarified that the quality of data should be “sufficient to support the decision-making process”. The previous EMA and FDA guidelines around risk-proportionality have been discussed in CRfocus, but Fergus also mentioned draft guidance from the OECD and EMA guidance that was expected to be published shortly, relating to the context of GCP inspection findings and how to assess whether they a finding would be more or less likely to impact on the overall risk/benefit decision on a medicine.

Finally, Fergus spoke about data transparency, which is currently a hot topic. He told us that guidance on the publication of summarised trial results had been published and would be implemented in 2013. He confirmed the intention of the EMA for clinical study reports to be made public once an MAA is approved. This story has moved on since this presentation, and will be reported in more detail in a future issue of CRfocus.

Jacques Demotes spoke next, giving additional details around the ECRIN project, which he coordinates. In particular, he highlighted that the project is attempting to address some of the barriers to international cooperation related to gaining access to expertise and patients, particularly for academic studies, throughout Europe. This is despite issues around national-level funding leading to fragmentation.

The ECRIN Integrated Activity (ECRINIA, www.ecrin.org/index.php?id=141) project is the next step in ECRIN’s development, funded by the EU under the FP7 programme. This is designed to build a consistent organisation for clinical research in Europe, with ECRIN developing generic tools and providing generic services to multinational studies, and supporting the construction of pan-European disease-oriented networks. There will be 16 networks in specific disease areas, to be set-up by 2015.

Elaine Godfrey of the MHRA went on to discuss trends around studies in the UK. In particular, she highlighted a decrease in the number of phase 1 studies being conducted in the UK, an area where the country has traditionally been strong. While this could be related to an overall decline in the number of studies being conducted in Europe, an initial review suggests that this might also be due to the trend to ‘roll-up’ studies into a single protocol, which might encompass multiple stages of phase 1 study and perhaps initial phase 2a studies. Elaine told us that an internal survey is currently underway to determine the extent of this ‘rolling-up’. (We hope to publish an article on this in a future issue of CRfocus.)

Elaine also discussed the Voluntary Harmonised Procedure for coordinated regulatory approval of multi-centre clinical trials across Europe. This was developed by the Clinical Trial Facilitation Group, which comprises the heads of regulatory agencies in each member state. VHP has been discussed extensively in CRfocus over the past 2 years, and its pilot has been considered by many to have been a success. As a result, a similar model for coordinated approval is now included in the proposed text of the new EU Clinical Trials Regulation.

Bringing this session to a close, Didier Caizergues, Director of Regulatory Affairs at Généthon shared his views on developing an Advanced Therapy Medicinal Product (ATMP). This product area has had its own regulatory structure since 2008, when Regulation EC/1394/2007 came into force. However, much of the disharmony that has been addressed in the regulation and oversight of conventional medicinal products has some way to go for ATMPs. In particular, Didier pointed out that the standard dossier format is not compatible with some genetically modified products, such as those involving modification of patient cells. Similarly, and perhaps unsurprisingly, the different specialist bodies reviewing ATMPs in different member states each have their own information requirements. In addition to having to process all these different dossier formats, the reviewing bodies do not coordinate their questions, leading to similar questions being returned from many organisations… which, in turn, need to be answered in different formats. As someone who has watched the development of VHP with great interest, this is precisely the kind of coordinated activity that Didier was calling for. However, given the relatively small number and high diversity of ATMPs currently in development, it might be much more difficult to put such a system in place for ATMPs.

Challenges for pharma

In the final segment of the programme covered by this report, senior representatives from British and French pharma companies discussed some of the national and international challenges facing them and shared their approaches to them.

Malcolm Skingle, Director of Academic Liaison at GSK, started by looking at the consolidation of the pharmaceutical industry since the 1980s, concluding that no company can do it all. As a result, his role within GSK is to facilitate partnerships. These can pair pharma companies with academia, biotech companies or even other pharma companies. Malcolm highlighted GSK’s focus on biopharmaceuticals and on rare diseases, but more interestingly he mentioned more diverse partnerships, such as with the Formula 1 racing team McLaren! This has contributed to GSK’s thinking on areas such as rapid prototyping and pass/fail testing.

Patrick Tricoli is Head of Scouting & Partnering at Sanofi. He characterised the past decade as being full of “much science and much information, but little patient benefit.” He picked up the theme of open data from earlier in the day and spoke of open innovation, which enables partners to share pre-competitive knowledge. As was the case with eHealth records, the key to making open innovation viable is the interoperability of organisations’ knowledge systems. Patrick called on us to rethink the traditional linear model of drug development, moving to a more cyclic model, linking patient outcomes back into subsequent research. He also highlighted the potential for scientific synergies with vaccine researchers, other types of biotech companies and even animal health companies. Patrick suggested that these could be coordinated in integrated R&D hubs.

Other presentations

There is insufficient space to report on all the presentations from this interesting symposium. In addition to the speakers above, Prof. Robert Lechler and Prof. Betrand Fontaine spoke about the potential for academic healthcare institutions to generate more value from their translational medicine activities, while Mike Capaldi and Francois Ballet spoke about how bio-clusters can bring academia and industry together more effectively.

Other breakout sessions included discussions about methodology and management of orphan diseases, biotherapies in auto-immune diseases and therapeutic innovation for Alzheimer’s disease.

Overall, while demonstrating that our two countries are facing similar challenges and responding in broadly similar ways by facilitating closer links between industry, academia and healthcare services, it was clear that there is much that we can learn from each other.

I am grateful to the French Embassy to the United Kingdom for the invitation to report on this event. For further information about Franco-British events relating to science and technology, please visit www.ambascience.co.uk.