Hugo Cervantes of Deloitte on reversing the decline of IRR in pharma R&D

A new report from Deloitte looks at the decline in Internal Rate of Return (IRR) across pharma R&D, and suggests that improving late stage success rates has a far greater impact than reducing cost or development times. We spoke to Hugo Cervantes, one of the leading contributors to the report, about what these findings mean, and what pharma can do to improve the situation, from closer collaboration to a sharper focus on value throughout the development process.

Triumph of the Market over Science?

One of the most significant news items of the past few weeks was the announcement that Geron will discontinue development of its stem cell products in favour of its portfolio of novel oncology compounds. This news comes less than 18 months after Geron received approval to conduct the first ever clinical trial involving embryonic stem cells, which made it the “poster child” for the sector and gave hope to patients with spinal cord injuries and (indirectly) many other degenerative diseases for which stem cell products are considered to be the most likely route to a cure. This is a significant setback, which will send ripples far wider than the company itself.

It doesn’t seem that the decision was made on the basis of the underlying science, or even the specific compound, being flawed. Indeed, less than a month ago the company gave a positive update on the phase 1 trial on its spinal cord injury treatment. Instead, the announcement spoke of “the current environment of capital scarcity and uncertain economic conditions” and that the decision was made “after a strategic review of the costs, value inflection timelines and clinical, manufacturing and regulatory complexities“, concluding that the move was necessary to ensure there was “sufficient financial resources to reach these important near-term value inflection points for shareholders without the necessity of raising additional capital.“  In short, they chose to focus on less controversial products that are further ahead in their development rather than a product stream with more question marks over its regulatory and political acceptability that might “kill the company” before making it to market.

This was, of course, a pragmatic and sensible decision for a publicly-listed company to make on behalf of its shareholders. However, it is a saddening decision for the science as a whole and sends a worrying message about the capability of the biomedical industry to pursue the step-change type of innovation that it needs in the long-term.

In the near future, companies need to replace their current portfolio of blockbuster drugs (which are effectively “one size fits all”, and were introduced with relatively few constraints on pricing) with a larger portfolio of products, with their price tightly linked to effectiveness in precisely defined patient groups. This presents a set of managerial and economic (and, to a lesser extent, scientific) challenges which, although complex,  are meat and drink for the analysts who drive the investment community. However, this line of development will only get us so far before we hit a barrier where the cost of demonstrating safety, efficacy and value at the individual level outweighs the revenue these products can realise. There is only so much more efficient our clinical development can be…

Then we will need entirely new technologies enabling us to address areas of therapeutic need that are otherwise effectively unmet, such as stem cell technologies. While Geron’s decision is probably the right move in difficult circumstances, it is imperative that it does not provoke the entire industry (or, more importantly, the entire investment community) to shift away from this area of research. Geron shows some degree of commitment to this with its intention to sell or license its stem cell assets to other players, but for this to succeed the investment community needs to have more courage in addressing the regulatory, political and commercial unknowns around stem cell products and to extend its horizon for a return on its investment in this important area.

In the current economic climate, this is a “big ask” but the long term consequences of not doing so would be worse all round.

“Rumours of the demise of European clinical research have been greatly exaggerated”

This is not the piece I anticipated writing when I sat down… For the past few weeks, I have been a false harbinger of doom! My apologies to everyone I have spoken to about a “sharp decline” in clinical research in Europe: I have led you astray and caused you undue concern… and all for the sake of insufficiently thorough research.

It all began in June when, on my routine check of the EudraCT website, I spotted that the latest batch of usage statistics had been published (https://eudract.ema.europa.eu/docs/statistics/EudraCT_Statistics_June.pdf). I looked specifically at the metric given for the number of new EudraCT numbers issued since the start of the year, as a reasonable surrogate for the level of clinical research activity around Europe over the coming 18 months. As a “half year” figure is mildly more reportable than other periods, I decided to compare this figure with those from previous years (https://eudract.ema.europa.eu/document.html#statistics). Imagine my surprise, not to say concern, when I worked out that the latest published figure was more than 70% down on the same period in 2010! Keen to check that the first half of 2010 hadn’t been a bumper year for EudraCT, I checked the same mid-point of the few years before that, and in each case found they were broadly similar.

So, in ICR’s weekly news bulletin and in conversation, I duly reported this “fact”, with the intention of writing a piece such as this to explore the reasons for this sharp decline. It was only when double-checking my figures before sitting down to write, that I spotted my error. I pulled together the published metrics for every month since January 2007, hoping to draw a neat trend against which the current figure would be a distressing contrast. I did find a trend: downward, by around 30% from 2007 to 2010.

But then I looked at the 2011 figures. For the first time, current metrics were broadly on-track with those from the previous year. In this context, the June figure that caused me such concern must surely be a transcription error (I have alerted EudraCT to my suspicion, and I expect that they will republish a corrected version of the report in due course), and it looks entirely possible that 2011 could be a turning point for clinical research in Europe. With the cost-gap narrowing between European sites and their competitors in other regions, and the European Commission and national governments alike entirely convinced of the need to streamline regulation and governance processes, it seems that the rate of sponsors leaving Europe to conduct their studies is slowing.

Of course, things will never return to the levels of activity that we saw in the 1990s and early 2000s: the “globalisation genie” is out of the bottle, and a significant proportion of research will continue to be done in the BRIC countries and surrounding regions (for good reason: there are plenty of patients there, who will take part in a clinical trials and, later, form the target market for the drug). But, on a closer analysis of the EudraCT metrics, rumours of the demise of European clinical research have been greatly exaggerated!

Multinational Studies Need Multinational Professionals

The proportion of industry studies taking place in a single country, with the exception of small early-phase studies, has decreased significantly over the past decade or more. This has been an inevitable consequence of globalisation, and if the studies are conducted to the same high standards of ethics, professionalism and data quality, then this is surely a good thing. However, multinational studies have more complex management structures and operate in more diverse environments of national regulation and oversight. Many people working on such a study would have tasks and accountabilities in several of these different environments, and those responsible for the overall conduct of the study must have an appreciation of the differences of approach that are required beyond the level of similarity driven by SOPs. An outcome of this is the evolution of a new generation of professionals with skill sets that didn’t exist 10 years ago. This is the age of the “multinational professional”.

The globalisation of clinical research driven both by demand (ie, pharmaceutical companies wanting more information and experience of new markets in which they hope to sell new drugs) and supply (ie, investigators in more countries wanting the intellectual, therapeutic and financial rewards that taking part in clinical trials can bring for themselves and their patients). The decision to include a new country in a global development programme (as distinct from the decision to exclude an incumbent country) says more about strategic changes in the pharmaceutical market than about the performance of traditional countries: the bigger picture includes dimensions beyond short-term cost and speed of completion. This means that the large, emerging markets will continue to play an increasingly significant role in clinical development, regardless of the success of performance-enhancing initiatives in the UK and other traditional locations. (It’s not a zero-sum game, of course, and countries such as the UK are specialising in the types of study that are most relevant for the national population, and the complex studies that are harder to do in less experienced countries.)

However, there are skills gaps emerging as a result of globalisation. It is well understood that many emerging countries have large numbers of physicians but relatively few of them, and even fewer of their support personnel, have clinical research training or experience. (This is an area where ICR is making a difference, both in our joint venture with the Pan-Asian Clinical Research Association, PACRA, and via our new Global Trainers’ Network.)

The skills required to set-up and monitor investigational sites in emerging countries are also in relatively short supply. While this gap is also being bridged, with global CROs working with, supporting and sometimes acquiring local organisations, the medium-term will still see many experienced professionals either relocating to developing regions or country-hopping to monitor a study in multiple countries.

Thirdly, a whole new set of skills is being developed to manage all these activities. Managers (often based in “traditional” locations) need to develop robust project plans that are more clinically complex than their predecessors but also more complex in terms of diverse national regulations, healthcare organisational structures and cultures, as well as increased logistical complexity around supply of study drug and handling of samples. Management of global teams to deliver these studies also requires skills that were rare a decade ago, such as handling remote team meetings, cross-cultural performance management etc. Increased use of technology makes much of this possible, but this technology also requires new skills to use effectively.

This is not a change that is just beginning: it has been going on for several years and is now effectively the “new normal”. A poll is currently running on the front page of the ICR website (www.icr-global.org) which asks about the proportion of working time spent managing sites or studies outside the country where the respondent is based. The poll is still open and, although the number of responses is still relatively small (n=40 at the time of writing), the trend is clear:

• Fewer than 25% work entirely within their own national borders.
• Over 50% work “mostly” or “entirely” outside the country where they are based.

This topic, and the skills that we need to work effectively within this “new normal”, is one that ICR hopes to discuss in more detail at an event in the near future. This is the age of the “multinational professional”; we need more of them, and in all likelihood it is people like you who will be in the forefront of our profession’s next generation.

How Much Does a New Medicine Really Cost?

If you meet someone at a party and say you work in clinical research, the chances are you’ll be asked “why are medicines so expensive?” The commonly accepted answer to this is “because it costs so much to develop them” but this has become so much of a mantra that we often accept it without really analysing or questioning the underlying figures.

The estimate that is generally accepted and used by industry was last published in 2003 by DiMasi et al,¹ which reported an average cost of $802m and has subsequently been adjusted (albeit only for inflation) to the $1b figure that we all quote. In fact, PhRMA the US trade association calculated a figure of $1.32b in 2006. However, a paper² was published last month that reworks some of this same data, and suggests that the true cost might be much lower: close to $55m! This paper has been picked up by some media outlets and provoked something of a furore… and opened an interesting discussion³ about how such figures are calculated.

There are a number of major differences between the assumptions and modelling methods used in the two analyses. These are discussed in much more detail online, but to summarise:

• Light and Warburton only consider the cost of the development process, excluding the costs associated with discovery/in-licensing and pre-clinical development.
• DiMasi et al assume clinical development and (FDA) regulatory submissions take a total of 7.5 years. Light and Warburton assume this takes 4 years.
• DiMasi’s analysis uses the mean of submitted cost data, while Light and Warburton use the median, which they argue reduces the impact of outlier costs.
• The groups’ treatment of tax on R&D expenditure is different.
• Light and Warburton model the cost of obtaining capital at significantly lower rates (3%, 5% and 7%) and DiMasi (11%). This is consistent with US and Canadian government guidelines, but some commentators think that this figure is unrealistically low for a sector where so few products entering development ultimately reach the market. Indeed, the cost of capital and the opportunity cost of not investing it elsewhere makes up a significant proportion of DiMasi’s estimate.
• Light and Warburton based their model on a “typical cohort” of 100 approved drugs, including a proportion of non-NME drugs which would have significantly lower development costs.

As with most things, some may have political reasons for wanting to portray development costs as very high or very low, and a more accurate estimate would almost certainly be somewhere between the two. Many of the assumptions and methods of Light and Warburton’s paper have been strongly criticised in comments. Based on anecdotal evidence from individual studies and ‘quick and dirty’ modelling based⁴ on benchmarking data published in 2006,⁵ contributors gave an estimate of $100m for the clinical studies required to bring a single drug to market. Again, this is low compared with the DiMasi figure because it excludes costs for discovery, pre-clinical, pharmacovigilance, cost of capital etc.

Another interesting question is how we might expect these costs to have changed since 2000, aside from simply adjusting for inflation. Studies are typically becoming more complex and thus more expensive; however, increased use of technology and automation should have reduced the cost of some activities. Increased outsourcing has enabled pharma companies to be more agile and save on total personnel overheads; however, paying for study teams CROs or staffing agencies would be expected to increase the per-study personnel cost. Similarly, changes in the wider economy may have influenced the attitude of investors towards the risks of drug development compared with other areas of technology; this might make DiMasi’s 11% too high for the current conditions or, indeed too low, given the prospects of reduced pharma revenues as we hit the ‘patent cliff’. The increasing globalisation of clinical development would also be expected to reduce the per-study costs, although the short-term net financial impact on pharma companies would be at least partially offset by restructuring costs.

So, comparing Light and Warburton’s $55m with DiMasi’s $1b is actually rather like comparing apples with oranges. Each may have some of their assumptions correct, and controversy remains over which has the more accurate methodology. On balance, many reading this will tend to side with DiMasi’s analysis, but as this is based on data nearly a decade old and pressures on price and value have never been stronger, perhaps now would be a good time for a really rigorous and industry-validated answer to the question of “how much does a new medicine really cost?”

References

1. DiMasi J, Hansen R, Grabowski H (2003): “The price of innovation: new estimates of drug development costs” J Health Econ 22 (2): 151–85. doi:10.1016/S0167-6296(02)00126-1 [Accessed March 8^th 2011]
2. Light & Warburton (2011): “Demythologizing the high costs of pharmaceutical research”, BioSocieties 6: 34-50; advance online publication, February 7, 2011; doi:10.1057/biosoc.2010.40 available via www.palgrave-journals.com/biosoc/journal/v6/n1/pdf/biosoc201040a.pdf [Accessed March 8th 2011]
3. Noah T (2011): “The Make-Believe Billion”, Slate http://www.slate.com/id/2287227/ and subsequent comments [Accessed March 8^th 2011]
4. Ibid, comment by “Guosong Liu”
5. Cutting Edge Information (2006): “Clinical Operations: Accelerating Trials, Allocating Resources and Measuring Performance” Press release published on LifeSciencesWorld www.lifesciencesworld.com/news/view/11080 [Accessed March 8th 2011]

 

Survey: Investigational Medicinal Product (IMP) management at clinical trial sites

You are invited to participate in a survey (http://www.zoomerang.com/Survey/WEB22AH7WMBA6D) to assess common practice of Investigational Medicinal Product (IMP) management at clinical trial sites for trials sponsored by the pharmaceutical industry.  This covers both the sponsor and the site perspectives.

Through personal experience managing clinical trials, questions received whilst serving on the Institute of Clinical Research (ICR) GCP Forum Steering Committee and through auditing and quality management work over recent years, it is clear that there is no consistent approach to managing or monitoring IMP at trial sites.  Investigator teams and monitors are therefore subject to a multitude of practices, which can give rise to frustration on the part of both investigator/pharmacy teams and sponsors/monitors alike and potentially put clinical trial subjects at risk.

There are 44 survey questions, which should take about 15 minutes to complete.  The survey is anonymous and the results will be shared through publication in CRfocus and on the ICR website. It is hoped that this will lead to future discussions on IMP management best practice and at least provide a benchmark from which to improve clinical trial IMP management in the future.

To complete the survey now, visit http://www.zoomerang.com/Survey/WEB22AH7WMBA6D

If you do not have time to complete the survey yourself, please consider forwarding it to a friend or colleague who might also be interested (they do not have to be an ICR member).

Thank you for taking the time to read this request and, hopefully, for also completing the survey.

[Posted on behalf of Janice Hedgecock MSc MBA FICR MRQA, Director and Clinical Development Consultant, Greatspur Clinical Development Ltd]

Science, Society & Economics: Shaping the Future of Clinical Research: ICR 31st Anniversary Conference & Exhibition

It’s that time of year again: here at the ICR office, we are making the final preparations for our Annual Conference, which is just a few weeks away on April 19^th and 20^th. The conference is ICR’s flagship event, and a high point of the year for clinical research professionals. Delegates, speakers and exhibitors come to learn about and discuss the issues facing professionals in their work designing, managing and conducting clinical trials.

The past couple of years have been challenging for us all, in terms of time and budget to invest in our professional development and networking. We’ve listened to your feedback about previous ICR conferences, and have built on the changes we introduced last year to give you the best event possible, with a programme of relevant and informative sessions for all the diverse roles making up the ICR membership. The 2010 ICR conference makes it easier for you to reconnect with your profession, and create new opportunities for yourself and your company.

After several years in the centre of England, we are bringing the conference to London for the first time in its history. This recognises the fact that more than half our members live within a couple of hours of the city. The Hilton Metropole, a few minutes away from Paddington station, is within easy reach of national and international transport services, whether you’re coming by car, train or plane.

For the first time in nearly a decade, the conference will be held in the hotel where most of the delegates, speakers etc. are also staying. This meant that we were able to offer delegates who booked their places early preferential rates on their hotel reservations. You also have the benefit of being able to carry on discussing issues after the conference formally closes, at our networking drinks reception on the Monday evening, in the bar or over dinner, or even over a shared breakfast before the second day of the conference opens.

Another important change is that we’ve frozen delegate prices to remain at their 2009 levels, to help members in these challenging economic times. This makes the ICR conference even better value for money than other multi-stream conferences.

If you can only go to one conference…

This year, we have a varied selection of relevant, knowledgeable and experienced speakers to discuss the important issues facing us all. All of the topics to be discussed at this year’s conference will impact on the way you work now and in the future, either directly on indirectly. Whatever your role in clinical development, and whatever point you’re at in your career, it’s vital that you stay up-to-date with the latest developments and make your voice heard in the discussions about their implementation, impact and implications.

The overarching theme of the conference is that clinical research is influenced by both internal and external factors, with economics and politics often having as great an impact on the way we work to develop new treatments as developments in medical science and operating procedures. The interfaces between these areas will provide the clinical research community with its greatest challenges, and its greatest opportunities, over the coming years.

Plenary sessions: Personalised healthcare & Health economics

Plenary sessions on key topics will close each day’s proceedings.

In the first of these, speakers from AstraZeneca and Roche will look at personalised healthcare, certainly an indicator for the way many future medicines will be developed and studied. The technological, scientific and clinical advancements in pharmaceuticals R&D over the past decade has ensured that the concept of personalised healthcare is now rapidly becoming the practice of personalised healthcare, particularly in infectious disease and oncology. This important field has implications reaching into patient recruitment and informed consent, pricing and economics, biomarkers and companion diagnostics etc.

The second plenary session will close the conference with a detailed look at the economic evaluation of healthcare technologies, which is increasingly used to inform social choices about access to innovative treatments. This is a field where the UK leads much of global thinking. Professors Richard Lilford and Karl Claxton, both of whom are close to the development of these ideas and their practical application, will discuss which health technologies should be approved or covered for use, what price ought to be paid for such technologies and how much and what type of evidence is required to support coverage or approval. The changing health-economic landscape will have an increasing impact on which clinical development programmes take priority, how individual clinical trials are structured, and how additional kinds of information need to be collected and analysed.

Parallel sessions: From patient recruitment to research governance

There are too many exciting topics being covered in the 12 parallel sessions to discuss them all in detail, but here is a selection of sessions that are proving popular with early-registering delegates:

Dr Clare Morgan of the NIHR Clinical Research Network Coordinating Centre will review what the NIHR CRN is doing to improve reliability, including improving confidence around quality study feasibility assessment, access to a wider pool of committed investigators with dedicated, trained resource to support study delivery and proactive study performance management.

Gaynor Anders and Prof. Theo Raynor urge us to “think outside the box” about patient recruitment. Real progress is being made on several fronts of the challenge to meet the study participation needs of research programs. However, there is still a huge gap between those needs and the collective willingness and ability of patients to enrol in studies.

Mark Lewis MICR and Christine McGrath MICR will explore the challenges and tactics involved in applying policy-level initiatives in practice at individual Trusts, to enhance and streamline UK clinical research. They will also discuss how to improve the performance of individual R&D departments (in terms of quality, speed, added value etc.).

Another key update will come from Janet Wisely of NRES, who will discuss the latest developments in ethics review. She will look at the ongoing development of the IRAS application system, the 2009 pilot scheme in proportionate review, and the use of ethics advisers to help committees work more effectively by ensuring that proposals are well presented, with scientific referees’ reports if necessary.

Other sessions consider practical issues, such as the role of research nurses in the informed consent process, the changing clinical data requirements for medical devices, managing remote teams and the move towards risk-based inspections.

Full abstracts and speaker profiles for all conference sessions are available at www.icr-global.org/community/conferences/31st-annual-conference-exhibition.

Annual General Meeting: May 19^th

The ICR Annual General Meeting has traditionally been an important part of the Annual Conference. However, as announced last month and clarified elsewhere in this issue, we have decided that this year’s AGM deserves more time and attention than it can easily be given alongside the conference. Instead, the AGM will be held at the ICR office in Bourne End, on May 19^th, starting at 5pm. Further details will be published to members in due course.

More targeted exhibition

In addition to attending conference sessions and networking with your peers throughout the industry, many delegates also come to the conference to find out more about potential new suppliers, and the exhibition has always been an important addition to the ICR conference. This year’s exhibition is already sold out, and we are pleased to have the support of so many companies from throughout the clinical research sector.

However, after listening to your feedback over previous years about the balance of exhibiting companies and the sometimes overly intrusive attitudes of a few individual stand personnel, we have decided to reduce the size of the overall exhibition, and particularly the proportion of recruitment agencies that have been invited to exhibit. Along with our Exhibitors’ Code of Conduct, this means that you will be able to walk through the exhibition aisles without concerns, and decide without pressure which companies you’d like to talk to.

Make the most of your membership

As I write this piece, in March, many of you have already registered to attend the conference, and it is becoming obvious that several of the sessions will be well attended. If you are struggling to find the time (or the budget) to come to the full meeting, we are offering single-day conference passes at reduced rates.

As we hope you’ll agree, this year’s Annual Conference will have something for everyone: plenty to learn, plenty of business benefit, but also plenty for us all to enjoy. We are also offering special reduced rates for professionals working in academia or the public sector, and to full-time students. To reserve your place, simply fax back the form on the back of the conference flyer enclosed with this issue of CRfocus, or register online via the ICR website (www.icr-global.org/community).

My full comment to Nature Medicine on UK competitiveness…

A few weeks ago, I was contacted by a journalist writing up a news item for Nature Medicine on the drift in the UK’s competitiveness in clinical research, and the measures being taken to address it. I wrote a response, which I knew was far too long.

This morning, I read the news item as it made it to print in the February issue of Nature Medicine (http://www.nature.com/nm/journal/v16/n2/full/nm0210-134b.html). I knew that my comment was far too long for its subtleties to make it through into the printed version, but it might be useful to publish here the full text of what I said…

It is undeniable that the UK now provides a smaller proportion of patients to clinical trials than was the case a decade ago. To ascribe this to internal changes, though, oversimplifies the issue. The efforts to streamline clinical trial authorisation, start-up etc. have been successful, in that without them the impact of external factors would have been even greater.

Over the past decade, many additional countries (particularly the BRIC countries, Brazil, Russia, India and China) have entered the marketplace as locations for clinical trials, offering access to patients at a numerical scale, rate of randomisation and cost-per-patient that mature markets could not hope to match. Cost advantages are decreasing as these countries develop, but demographic advantages remain.

At the same time, standards of conduct have been raised, with the aim of increasing protection of clinical trial participants. Key developments have included the ICH Good Clinical Practice guideline (1997), the EU Clinical Trials Directive (2001, implemented 2004) and the various versions of the Declaration of Helsinki (most recently in 2008). In the UK, public concern following scandals such as Alder Hay also raised the priority of research governance for the Department of Health and NHS Trusts. These developments have made it much harder to conduct poor quality research, a publicly desirable outcome, albeit with increased administrative costs and (more importantly for clinical trials of patented products) timelines.

These factors, one an inevitable consequence of globalisation and the other clearly desirable, have impaired competitiveness in the UK and indeed throughout the developed world.

There is also a demographic aspect: clinical trials collect evidence that is hoped to demonstrate that a product will be effective in a given patient population, but also in the specific healthcare delivery regimen and socio-economic setting of its intended market. Drugs entering clinical development now could hope to receive regulatory approval in the early 2020s, by which time the increasingly numerous and affluent middle classes in the BRIC countries and beyond could comprise a market of equal or greater value to traditional markets in the “developed world”. If their economic development continues, conducting clinical research in these countries there will become more important regardless of any improvement in productivity in the UK, other EU countries etc.

All of these issues are having an impact on inward investment to conduct clinical research in the UK. With investigational sites in all countries competing to recruit the total number of participants required for a study, slow sites in the UK can lose out to quicker sites elsewhere, with payment following patients. In addition, some pharmaceutical companies and contract research organisations (CROs) are compiling lists of “preferred” countries in which to concentrate their research activities, mainly based on prior performance, and the UK is not always on these lists.

However, much has been done to address this. Common systems to submit study protocols for regulatory and ethics approval, guidelines to improve transparency and consistency of study costs, standardised contract terms, coordinated networks to share expertise and resources, and enhanced infrastructure and structured development and training for clinical research professionals are all having an impact. Implicit in this is the acknowledgement that there are certain therapeutic areas and types of clinical trial where UK sites do still perform well and add value, and it is in these areas where future efforts and investment should be concentrated.

There are still improvements to be made, and the next wave of initiatives were set out last summer in the Office of Life Sciences’ Blueprint. In addition, a process to review the EU Clinical Trials Directive has just begun, with a view to increasing harmonisation of regulation across the EU and reducing the administrative burden of compliance, without sacrificing protection of study participants.

It would be unrealistic to expect the UK to have maintained pre-2000 levels of competitiveness in the face of such strong external factors. Efforts are continuing with the aim of improving absolute performance, but the societal value of improved participant protection should not be understated. The UK should continue to focus its efforts on therapeutic areas and types of study where it performs best and adds most value.

In the first round of feedback with the journalist, I picked up on the aspects that he found most useful, and wrote a couple of summaries on those areas:

• “Like the rest of the economy, clinical research has globalised in the past decade, with rapid access to high numbers of patients now possible in countries that saw virtually no clinical research 15 years ago,” says Andrew Smith, editor of Clinical Research focus, published by the Institute of Clinical Research. “UK initiatives have succeeded in partially offsetting this, but when more competitors enter a market the leaders’ performance tends to be diluted.”
• The conduct of trials was also tightened up by international initiatives such as the ICH Good Clinical Practice guidelines and EU Clinical Trials Directive. The implementation of these into law, in the UK and elsewhere, have increased the administrative burden of clinical trials but have “made it much harder to get away with conducting poor quality research, which is a publicly desirable outcome,” Smith says. Current initiatives are trying to make compliance less costly without compromising patient protection.

I wouldn’t want my publication of this to be seen as criticism of the reporter or his editor, but I would like to get the finer detail of my points “out there”, so readers don’t misunderstand the balance of my views on clinical research in the UK, its recent difficulties, and the efforts that are being made against strong economic forces.

Table of Contents: CRfocus 20(10) – October 2009

This is the Table of Contents of Clinical Research focus 20(10) issue for October 2009. Members of The Institute of Clinical Research can view the full text of each article by clicking the link and logging in with their username and password.

Global competition

Multinational Trials: A New Balance Point?

Andrew Smith

Given that multinational (often ‘massively multinational’) trials are now the default position for anything beyond the earliest phase of clinical research, it is somewhat surprising that they still polarise opinion. To some, they are the only way to complete large studies even remotely on deadline and within budget. To others they are damaging to local professionals and research infrastructure and of limited clinical relevance to a medicine’s target patient population. In this extended editorial, Andrew Smith takes a look at the evolving bigger picture of globalising clinical research and suggests how we might find a new balance point to deliver global performance combined with local relevance.

Managing Clinical Research in the UK: Survey & Conference

Andrew Smith

There are many layers of perception and received opinion characterising the UK’s performance, with a basic view that we are not performing as well as we might in comparison to other countries (generally in terms of being slower and/or more expensive) and are losing business as a consequence. However, much of the evidence for this is anecdotal, and where metrics do exist they are often specific to an organisation, therapeutic area or part of the process (eg, final protocol to first patient visit). A one-day conference was held in September to discuss initial results of a 2-year study that looked across the entire research process, encompassing both commercial and non-commercial research in all therapeutic areas. Andrew reports…

Feature

My Clinical Study is Over; What Happens to the Data? An Introduction to the Clinical Study Report

Emily Scott

Conducting a clinical study takes a considerable amount of planning, resource, and commitment. But, after the last subject is out, the database has been cleaned, and the planned analyses have been done, what happens to the data that were collected? For interventional studies conducted in accordance with the International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice (GCP), data collected in a clinical study should be submitted to the authorities in a Clinical Study Report (CSR). Emily Scott provides an introduction to CSRs, how they should be constructed and how other study personnel should be involved.

Prof. development

Study Management for Research Nurses: ICR Research Nurse Forum

Nicky Perry MICR

The ICR Research Nurse Special Interest Group (SIG) held their second forum on June 18th at the ICR office. Sixty research nurses attended. The agenda for the day was set following the training needs analysis conducted via questionnaire, which was sent out last year. The result of this survey highlighted that nurses wanted to know more about study management, especially how to cost a clinical study.

Virtual Learning in the Real World: ICR Tainers’ Forum

Iain Searle MICR CSci, Merryn Collard RICR & Jane Nathan RICR

ICR’s Trainers’ Forum generally holds three meetings each year, designed to address topical issues and challenges for those involved in training functions across health, pharmaceutical and life science industries and services. This event was prompted by the rapid development of remote delivery methods within our sector, with a wide range of solutions being implemented across the industry. The days’ agenda had been developed by the Steering Committee, which has a mission to support the interests and further development of trainers within ICR by providing topical meetings, with expert speakers from within and beyond the pharmaceutical industry.

Trial technology

Ten Things You Need to Know About Infusion Pumps for IV Delivery in Clinical Trials

Elena Skryabina

In the latest in our series of introductions to key topics, Elena Skryabina examines the use of infusion pumps for intravenous drug delivery in clinical trials. She demonstrates the amount of control that is possible in a single Phase I unit but also the care that should be taken in larger studies, where differing pumps at different sites can impact on the precision of study drug delivery.

Book review

“Trial by Fire: Lessons from the History of Clinical Trials”

Allan Gaw, reviewed by Andrew Smith

The rationale for this excellent little book is summed up by Mark Twain, quoted in the introduction: “The past does not repeat itself, but it rhymes.” Learning about the history of clinical trials helps us to understand why the present is the way it is, and this book provides insights into ways of thinking and working that many of us would otherwise simply take as given. It is written in a clear, readable style, with interpretation as well as factual account, highlighting the aspects of each topic that have had the most significant impact on the way clinical research is done today.

Regular update

Fit For the Future: Message from the Chair

Janette Benaddi MICR CSci

Like most organisations, the Institute has experienced a difficult operating environment this year, caused by the global recession. However, the Board of Directors and Senior Management Team (SMT) took early, proactive steps at the beginning of the year to manage us through the recession. These included a thorough overhaul of our operating costs and we are starting to see the benefits of these actions. Janette thanks you, our members, for your continuing support. We have received many communications from you supporting ICR over recent months, as we have gone through the change management process. The staff are extremely encouraged by this.

It’s Not All Work, Work, Work…

Compiled by Andrew Smith

Our regular look at the lighter side of clinical research, including some ideas for blockbuster movies involving clinical research, examples of “frontier science” in literary classics (and the new Dan Brown), and “Ten things that suggest global clinical research is starting to pick up again…”.

OLS Blueprint: PICTf 3.0?

The UK pharmaceutical industry is one of the most significant industries to make money for ‘UK plc’ and re-invest it back into UK-based R&D, within their own organisations, in universities and throughout the NHS. As many have said, the UK ‘punches above its weight’ in our sector. Despite this, we often feel unloved, in terms of both media and public opinion and increasing constraints on revenue (eg, prescribing decisions being led by NICE guidance while reimbursement rates have been cut under the successor to the PPRS). However, the counter-balance to this top-line constraint has come in the form of various initiatives to make more of a contribution in terms of investment in education and training, infrastructure and organisational processes. As a globalised industry has far less binding ties to doing its R&D in the UK than it did 30 years ago, this policy makes a great deal of sense. Over the past decade or so, these initiatives have come under the banners of PICTf, UKCRC and, now, the Office of Life Sciences (OLS) Blueprint, which was published over the summer.

The Blueprint set out 12 key action points, which have been agreed across government, industry, the higher education sector and the NHS. This expands to 10 pages of specific policy measures, complete with timelines and budgets. The Blueprint has been widely welcomed by industry and commentators alike, and certainly, every policy measure should have a positive effect.

The measure that has received the most coverage is the Innovation Pass, ring-fenced funding for time-limited use across the NHS without appraisal by NICE (although NICE will define the criteria for medicines that can take this short-cut). This will be piloted in 2010/11 with a budget of £25m. While initially portrayed by the media as bypassing NICE, this could be a valuable experiment in ‘live appraisal’ mirroring the ‘live licensing’ model proposed by PricewaterhouseCoopers in their Pharma 2020 reports.

The policy that will be of most interest to us in the clinical research sector is the “package of measures to improve the UK environment for clinical trials”. This includes ensuring the UK “fully exploits its potential to be a world leader in heath informatics” (ie, making electronic patient records finally happen!), underlining the duty for SHAs to promote R&D, adding metrics on patient in clinical trials to Trusts’ Quality Accounts, and creating a national framework for local management of research (ie, transforming NHS R&D departments). Significantly, the last three points are essentially reworking areas covered by PICTf nearly a decade ago…

The questions that need to be asked about all these measures, though, are “Will they be implemented as planned?”, “Will they result in improvements in the productivity of UK R&D and uptake of resulting products?” and “Are they sufficiently different from previous initiatives to justify the top-line reduction in reimbursement for medicines?” The many intelligent and powerful people close to this project evidently think so. Far be it from me to disagree, but the fact that this is the third major initiative in less than a decade suggests that its predecessors did not maintain momentum in their improvements (or, more cynically, that pharma are getting increasingly itchy feet in the light of increasing competitiveness overseas).

To sound another small note of scepticism, the UK is less than 12 months from a general election, with a change of government far more possible than at any time since 1997. Although many measures in the Blueprint can be implemented almost immediately, many will take time to demonstrate success, and none will be immune from reversal under a new government.

So, I would like to raise two cheers for the OLS Blueprint: it talks a good game and will certainly have some success, but will it be enough to steady ship of UK competitiveness or just the latest in a series of defences against an insuperable drift to merely “punching our weight”? We will see…