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Posted by Andrew Smith on November 29, 2011
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.
Posted in CRfocus, Drug development, Pharmaceutical development, Podcasts | Leave a Comment »
Posted by Andrew Smith on March 9, 2011
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:
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?”
Posted in "Clinical research", CRfocus, Drug development, Editorials, Pharmaceutical development | Leave a Comment »
Posted by Andrew Smith on July 12, 2010
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]
Posted in "Clinical research", Drug development, Pharmaceutical development | Tagged: clinical trials, pharma, Pharmaceutical development | Leave a Comment »
Posted by Andrew Smith on March 29, 2010
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 19th and 20th. 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.
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 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.
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.
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 19th, starting at 5pm. Further details will be published to members in due course.
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.
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).
Posted in "Clinical research", CRfocus, Drug development, Pharmaceutical development | Tagged: "Clinical research", conference, Ethics, Health economics, ICR, Paediatrics, Patient recruitment, pharma, stem cells | Leave a Comment »
Posted by Andrew Smith on February 8, 2010
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.
Posted in "Clinical research", Drug development, Editorials, medical journal, Pharmaceutical development, Quick thoughts | Leave a Comment »
Posted by Andrew Smith on July 28, 2009
ICH guideline E6 (ICH-GCP) is, along with the Declaration of Helsinki, arguably the most important document in clinical research. Although neither has any direct status in the legislation of most countries where clinical research is conducted, their principles (and in many cases more substantive details) set the tone for how pretty much everyone conducts clinical research. Since its adoption in 1996 (in Europe; 1997 in the USA and Japan), ICH GCP has been the ‘bible’ for CRAs, auditors and other clinical research professionals worldwide.
Since 1996…
The world of clinical research has moved on quite some way in the past 13 years, and even more so when you consider the period of several years that was taken for the drafting, consulting, reviewing and negotiating prior to the guideline’s finalisation. Other guidelines (most notably the Declaration of Helsinki) have been updated several times in the past decades, and have a timeline for regular review every few years.
So, following a remark made by a speaker at the ICR Annual Conference earlier this year, we wondered whether ICH E6 should be reviewed and potentially revised. We put a poll on the front page of the ICR website, and were rather surprised by the result: over 80% thought that it should be reviewed (although from an admittedly small sample). We are currently undertaking a qualitative survey, asking what elements of the guideline should be updated and/or what should be added that did not exist in 1996. We hope to publish this in September’s issue of CRfocus magazine. If you would like to share your thoughts on this, and contribute to our article, please send your comments to andrew.smith@crfocus.org no later than August 10th 2009.
Of course, this is to an extent a purely academic exercise: many of the assorted national legislations, EU Directive etc. are subtly different, and the feasibility of renegotiating such a complex document with so many stakeholders (not least the more recently research-active countries that are outside the formal ICH process) is highly questionable. Indeed, some contend that the national legal arrangements have become so much more formal and sophisticated than they were in the 1990s that any thought of change to a founding guideline like ICH GCP is futile.
Still, it is useful to consider what aspects of contemporary clinical research are poorly served by the current fragmented global network of regulation and guidelines, and how different ICH GCP would look if it were being created in 2009. I’m interested to hear what you think…
Posted in "Clinical research", CRfocus, Drug development, GCP, Pharmaceutical development, Quick thoughts | Tagged: "Clinical research", Drug development, GCP, Good clinical practice, ICH-GCP | Leave a Comment »
Posted by Andrew Smith on January 21, 2009
The CRfocus blog is pleased to be sponsored by the Institute of Clinical Research 2009 Annual Conference & Exhibition.
ESSENTIAL UPDATES
AND LIVELY DEBATES
ICR understands the importance of maintaining your competitive edge in the current environment. Therefore, this year’s conference is packed with opportunities to hone your professional skills, stay abreast of the latest regulatory developments and keep up to date with the hottest innovations in the clinical research industry.
There will also be plenty of opportunity for you to make new contacts and network with influential figures from across the industry.
Programme highlights include:
For details of how to register and to view the full conference programme click here
Posted in Drug development, Pharmaceutical development | Tagged: "Clinical research", clinical trials, conference, Declaration of Helsinki, Drug development, EU Clinical Trials Directive, Outsourcing, Pharmaceutical development, Value-based pricing | Leave a Comment »
