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.