Clinical Research insights from CRfocus

Blogging for Clinical Research focus, the journal of The Institute of Clinical Research

Posts Tagged ‘ICR’

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

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.

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 19th

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.

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).

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Table of Contents: CRfocus 20(11) – November 2009

Posted by Andrew Smith on November 25, 2009

This is the Table of Contents of Clinical Research focus 20(11) issue for November 2009. Members of ICR can click the links below to log in and read the full text of each article.

Features

Challenges of Inter-Organisation Projects: What Factors Lead Towards Success?

Matthew Theobald

Working with partner companies to define, execute and deliver a clinical research project can be a challenge at the best of times. So what is it that sets successful projects apart from those that struggle to get started or lose focus during their execution? Recent ‘project fractures research’ into this topic reveals that the root causes of project failure (or significant variance) don’t lie in the project management methodologies or structure. The root causes actually lie in the people factors, such as how they engage in projects. Matthew Theobald presents some useful insights into how projects fail, and suggests how they might be planned and managed better.

An Unacceptable Conflict of Interest? The PharmaTimes Great Oxford Debate

Les Rose FICR

Arguably the world’s foremost debating chamber, the Oxford Union was the scene of this annual event, which always addresses contentious issues for the pharmaceutical industry. The Motion for this year’s debate was: “This house believes that there is an unacceptable conflict of interest when pharma conducts trials on its own drugs”. Les Rose was there, and presents the main arguments for and against the motion, and reveals the (not unexpected) result of the evening’s vote.

How Will Personalised Medicine Have an Impact on Clinical Trials?

Abel Ureta-Vidal

How can genomics have an impact on the management of your clinical trials? With the growing understanding of genetic code within personalised medicine, could this signal a change in the size and scope of clinical trials? What does this mean for the pharmaceutical industry and the patient? “Personalised medicine” is a current buzzword, but what does it actually mean? Some say it has the potential to affect the entire landscape of our healthcare system over the next ten to 20 years. Abel Ureta-Vidal explores the potential benefits, but also the risks and challenges.

A Marriage Made in Heaven or Grounds for Divorce: ICR Project Management Forum

Sarah Muller MICR

Christopher Colombus, Kevin and Perry, men from Mars and women from Venus were all mentioned at the ICR forum on ‘A Marriage Made in Heaven or Grounds for Divorce: Exploring the interface between Project Management, Data Management and Statistics.’ This forum took the form of a debate on the motion “The data management and statistics functions are well managed by project management”. Following the formal debate, there was plenty of time for discussion between the speakers and audience. Sarah reports…

People

Exploring an Innovative CRO Business Model: An Interview

Susan Ollier HonFICR CSci & Paul Thompson

Paul Thompson is Director of Business Development and Susan Ollier HonFICR CSci is Director of UK Operations at QED Clinical Services. Many readers of CRfocus will know Susan better as Chair of ICR until she reached the end of her term at this year’s AGM, but she also ran a consultancy which recently merged with QED Clinical Services. We discuss the company’s franchise business model, the importance of cultural fit and the importance of commercial and operational innovation in the CRO sector.

Prof. development

ASM Posters: 2009 Entries & 2010 Submissions

Andrew Smith

The Institute of Clinical Research is pleased to announce that its 31st Annual Conference and Exhibition, with an overall theme of “Science, Society and Economics: Shaping the Future of Clinical Research”, will once again include a poster session. In this brief introduction to the 2010 competition, we present some highlights from the 2009 competition and invite you to submit an abstract for a poster at this year’s event. You can submit your poster abstract for consideration using the online form at www.icr-global.org/community/conferences/31st-annual-conference-exhibition/poster-abstract-submission/. The deadline for poster abstract submissions is Friday 5th February 2010.

10 Things You Need to Know About… Being Resilient at Work

Helen Chapman

Resilience is the ability to stay balanced and to bounce back quickly from setbacks and adversity. Resilient people stay committed and increase their efforts when the going gets tough. Some people are born naturally more resilient than others, but anyone can improve their resilience through effective awareness and training. This article will give you ten simple ideas for becoming more resilient to the ever-changing world around you and reassure you that a key aspect of being resilient is knowing that although you may not be able to change the environment around you, you can change how you choose to let it affect you.

Regular update

The Challenges We Face: Varied but Interlinked: Message from the Chair

Janette Benaddi MICR CSci

It is impossible for anyone to replicate the direct experience of all our members, not having worked in every sector. However, as Janette explains, she tries to understand the major issues affecting you and encourage you to become more involved yourself as opportunities arise for influencing the shape of clinical research. It is always interesting to learn that the challenges we face are often similar despite our diverse therapeutic fields and specialisations.

It’s Not All Work, Work, Work…

Compiled by Andrew Smith

Our regular look at the lighter side of clinical research, including reality TV formats to raise the profile of clinical research, pharmaceutical brand names that never made it to market and “Ten things that shouldn’t be used as project performance metrics…”.

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CRfocus: Table of Contents of July 2009 issue – 20(7)

Posted by Andrew Smith on July 6, 2009

CRfocus 20(07) – July 2009

This is the Table of Contents of Clinical Research focus 20(07) for July 200. Members of ICR can click the links below and log-in to read the full text of these articles

Outsourcing

The Evolution of Outsourcing: Contract Management Coming of Age

Andy Parrett

The contract management role in clinical development outsourcing is still a relatively young profession. The nature of the role can vary significantly between pharmaceutical companies. Andy Parrett, Chair of the Pharmaceutical Contract Management Group (PCMG) suggests that the most exciting developments in the role are occurring in today’s small to mid-sized companies, and looks at how the processes surrounding outsourcing and its successful management are being developed.

Features

EudraCT Upgrades to Version 7

Andrew Smith

An information day was held by the EMEA at the end of April, bringing together representatives of national Competent Authorities (CAs), pharma companies, CROs and non-profit stakeholder groups. The purpose of the day was to communicate the features and development timelines of the next few versions of the EudraCT database of clinical trials in the European Economic Area (EEA), which went live in mid-June. Andrew reports, based on blog postings made on the day of the meeting.

CDISC European Interchange 2009: Conference Sketch

Adam Jacobs FICR CSci

CDISC (the Clinical Data Interchange Standards Consortium) is a relatively new player in the world of clinical research, having been founded in 1997, but it is rapidly gaining in importance, and is here to stay. To keep up with some of the latest developments in the CDISC world, Adam reports from the European CDISC Interchange, held in Budapest in April 2009.

Quality Assurance: Friend or Foe? A Survey

Jan Robinson MICR CSci

No-one questions the need for quality assurance of clinical trial activities but as someone at the receiving end have you ever been asked your opinion of the process? In your view, is audit a positive force for improvement? Are they the best means of advancing best practice or should we be taking a different approach? Jan invites you to take part in a short survey, to be reported in CRfocus and at the BARQA annual conference later this year.

Writing Protocols: Collaboration & Compromise or Conflict & Confusion? ICR/EMWA Joint Symposium

Alex Dedman & Andrew Smith

The challenges of developing clinical trial protocols were the topic of the second annual symposium jointly hosted by the European Medical Writers’ Association (EMWA) and The Institute of Clinical Research (ICR) on 24 February 2009. Around 60 delegates discussed the difficulties associated with developing protocols that both meet sponsors’ scientific and regulatory requirements, and facilitate the practical conduct of the study. Alex and Andrew report for CRfocus and The Write Stuff, the EMWA members’ journal.

People

Why You Should Care About the Innovative Medicines Initiative: An Interview with Jackie Hunter

Edward Blair MICR

The EU Innovative Medicines Initiative (IMI) was established in 2007 and issued its first call for proposals in 2008. Funding for the successful proposal has been allocated and the work kicks off in June this year. So, the IMI is for real and is beginning to deliver, but how well known is it and why will it change the pharmaceuticals industry in ways that will benefit ICR members? To get a first-hand insight into the aspirations of the IMI, CRfocus talked to Dr Jackie Hunter of GlaxoSmithKline, who has seen the IMI develop from a twinkle in the eye of EFPIA into the operating entity that it is now.

Conference

We are pleased to include two more session reports from the ICR Annual Conference, which space prevented us from including in last month’s issue.

International inspections

Fergus Sweeney & Gunnar Danielsson

Reporter: Judit Varkonyi-Sepp MICR CSci

Organ Transplantation: Past, Present & Future

Prof. James Neuberger & Mr Simon Bramhall

Reporter: Ali Zataar MICR CSci

Regular update

The Board of Directors: Who Are They & What Do They Do?: Message from the Chair

Janette Benaddi MICR Csci

The Institute of Clinical Research has a legal status of “a company limited by guarantee” and this means that it has to be managed by a Board of Directors. As members, you may wonder from time to time what the ICR Board of Directors do, who they are and how they add value to ICR members. Janette answers these questions, explains how the Board operates, and confesses her early (now-achieved) professional ambition to be a Board Director herself.

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CRfocus: Table of Contents of June 2009 issue

Posted by Andrew Smith on June 3, 2009

CRfocus 20(06) – June 2009

CRfocus 20(06) front cover
This is the Table of Contents of Clinical Research focus 20(06) for June 2009. Members of The Institute of Clinical Research can click on the links to read the full text of each article.In previous years, we have endeavoured to publish reports on all conference sessions in this issue. However, due to constraints on page space and available reporters, we have decided to publish a balanced selection of reports in print, with others (and extended versions of printed reports) becoming available here during June.

Conference photo-gallery

Photos uploaded during the meeting, plus many additional images

Plenary sessions

Lively Debates & Votes:Day One Plenary Sessions

  • Niall Dickson, Prof. Karol Sikora, Prof. Nick Bosanquet, Francis Crawley & Colin Miller FICR CSci
  • Reporter: Suheila Abdul-Karrim MICR Csci

Pharma 2020: VirtualR&D

  • Kate Moss
  • Reporter: Andrew Smith

Lively Debates & Votes: Day Two Plenary Sessions [online only, coming soon]

Sharing knowledge

Off-Shoring in ClinicalResearch [extended version, online only]

  • Prof. David Jefferys & Paul Wathall MICR
  • Reporter: Wendy Tomlinson MICR

Stem Cells: Current Advances & Applications

  • Prof. Peter Andrews & Prof. Malcolm Alison
  • Reporter: Jane Pelly MICR Csci

Contracts in Global ClinicalTrials

  • Rebecca Sergeant & Sarah Watts
  • Reporter: Judit Varkonyi-Sepp MICR Csci

Electronic Data Capture (EDC): Issues & Practical Solutions [online only, coming soon]

The A-Z of Adaptive Study Design [online only, coming soon]

Fundamentals of PIPs [online only, coming soon]

Therapeutics

Oncology Care in the Future [extended version, online only]

  • Prof. Angus Dalgleish, Prof. Nicholas James, Prof. Jonathan Waxman & Prof. Will Steward
  • Reporter: Shethah Morgan MICR Csci

The Heart of Cardiology

  • Dr Mike Mullen & Dr Marcus Flather
  • Reporter: Sue Jackson RICR

The Heart of Cardiology [extended version, online only coming soon]

Organ Transplantation: Past, present & future [online only, coming soon]

Raising standards

The Impact of theDeclaration of Helsinki

  • Eva Nilsson Bagenholm MD & Bev Holt MD
  • Reporter: Rachael Winter RICR

Quality & Productivity:Can You Have Both?

  • Alison Messom MICR & Andrew Borrisow
  • Reporter: Wendy Tomlinson MICR

Evidence for Good Quality:The Hidden Cost of Inspection

  • Prof. Richard Gray & Joan Perou HonFICR
  • Reporter: Suheila Abdul-Karrim MICR Csci

International Inspections [online only]

  • Fergus Sweeney & Gunnar Danielsson
  • Reporter: Judit Varkonyi-Sepp MICR CSci

Putting a Price on Patient Value [online only, coming soon]

Inspectors: Why Do They Do It? [online only, coming soon]

Developing professionals

Medical Devices Workshop [online only, coming soon]

Image in Business: It’s Personal [online only, coming soon]

Project Management Workshop [online only, coming soon]

Leadership Workshop [online only, coming soon]

Regular updates

Session Reports from theICR Annual Conference: Message from the Chair

  • Janette Benaddi MICR Csci

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Twittering from the ICR conference next week

Posted by Andrew Smith on March 11, 2009

Next week will see the Institute of Clinical Research 30th Anniversary Conference & Exhibition, taking place on March 17th & 18th at the ICC in Birmingham. Of course, I will be there to:

  • Cover the meeting for CRfocus (along with a team of roving reporters!)
  • Help with the organisation and operation of the meeting (ICR is the parent organisation of CRfocus)
  • Chairing a session on the tension between pricing and patient value, and how you can accurately assess either

I also plan to Twitter live from the conference (I’ll be too busy to live-blog like I normally do from such meetings). You can see my most recent “tweets” on the main CRfocus webpage, or follow me on Twitter itself. I’m also hoping to have time to do some other neat things, such as one or two audio interviews with delegates or speakers, and post some photos live from the meeting…

This is going to be a great conference, and I’m looking forward to it immensely. If you haven’t registered yet, take a look at the conference programme, and come along (we have passes available from a half day up to the entire meeting).

I’d love to see you there…

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CRfocus on Twitter

Posted by Andrew Smith on March 4, 2009

Clinical research professionals can now keep up with CRfocus even more rapidly using the well-known web service Twitter. After several months of including CRfocus-related content on my personal Twitter page, I have now set up a dedicated CRfocus account (http://twitter.com/CRfocus).

You can visit that page for regular updates, see recent “tweets” on the main CRfocus page (www.crfocus.org) or ‘follow’ CRfocus through your own Twitter account.

It’s a great way to keep up with the fast-moving world of clinical research, particularly during the conference season…

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Sue Mackay on the study nurse view of trial protocols

Posted by Andrew Smith on February 24, 2009

Sue Mackay of CDSS leads a team of field-based study nurses, who deal with protocols on a practical level, often interacting with protocols when they are complete, and sometimes feels that she is trying to fit the square peg of a protocol into a round hole of practicality, and she thinks it a pity that more practical issues are not considered earlier in the process.

Sue described the typical role of the research nurse, listing the many activities that they do, from patient identification to AE reporting and data queries. She highlighted site study feasibility and protocol review as key areas for this conference.

A well-written and consistent trial protocol is very welcome, and makes the implementation far easier. As topics like subject selection and study procedures flow from protocols, advice on how they are done in the field could be flowed back into protocol development.

For example, she suggested that we could be missing patients because of slight differences in inclusion criteria; surely it would be better to consider this at a draft stage rather than asking for patient exemptions. She also discussed timelines of first visit to site vs time to consent: too short can be impractical but too long can cause identified patients to lose interest.

Similarly, timelines for study procedures and frequency of patient visits might not be feasible or acceptable for patients. Other hospital departments might not be flexible enough to meet the timelines of the protocol, given their primary role in general patient care.

Sue also suggested that we think about aspects of the protocol from the patient’s point of view: timing of procedures might not fit easiy with patients’ family and work commitments, in terms of duration and of time of day.

Sue again stressed the importance of clarity and consistency within the protocol, as it can cause confusion and waste time when the protocol is implemented. She gave an example of a ‘requested’ screening procedure in an asthma study that would not be routine treatment in that therapeutic area.

Next, Sue discussed subject selection and compliance. We need to be careful in where we place studies, that the site has access to the right type of patient. Similarly, is the duration of the study or the frequency of visits appropriate to the therapeutic area, eg, oncology patients perhaps deteriorating during the course of a study. She also discussed the implications of the economic conditions on willingness to take part in a trial: routine commitment to site visits during a trial might make a patient less employable, so they might decide not to take part.

Offering some solutions, Sue suggested more, broader communication is vital, although the route for communication between nurses and medical writers is less clear. Similarly involvement of other site staff (eg, labs, radiography, physiotherapy etc.) in protocol development would be beneficial. She reiterated the call for consistency.

In summary, she stressed that these ‘square pegs’ are people, and that they need to be considered more in order to retain their goodwill and willingness to take part in studies.

One delegate asked how site staff use a protocol; Sue answered that she requires her team to read the protocol and investigator’s brochure in detail and refer to them regularly, even though it is used in conjunction with other notes.

A project manager in the audience mentioned that she sends draft protocols to investigators, and was a little surprised that it isn’t circulated to the site study team at that stage. Perhaps research nurses could help to educate their investigators on consulting more widely at the draft stage. Sue agreed that it would be helpful to be more pro-active in this area. Another project manager in the audience said that it is difficult to contact study nurses directly, with contact going through investigators.

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Adam Jacobs on statisticians in protocol development

Posted by Andrew Smith on February 24, 2009

Adam Jacobs spoke next. Adam has a background in medical writing, but is also a statistician and sits on an ethics committee. His main point was that it’s never too early to ask a statistician.

Adam discussed military precision in writing protocols. The most important of these is to Keep It Simple. A protocol should be as simple as it should be and still achieve its objectives, for ease of implementation. Once an objective is selected, they must be maintained, with anything else being omitted. However, morale is also important, so its vital to keep key stakeholders informed, so that any problems can be identified early. Flexibility and contingency planning are also important, as is robust communication.

Adam went into communications in more detail, particularly for dealing with statisticians, who can seem to speak a different language to the rest of us! However, effective communication is vital. His top tip is that there is no substitute to face to face meetings. He said that statisticians are used to not being understood, and to explaining again if you let them know what you haven’t understood.

Adam described the statistician’s role: specification of objectives, trial design, analysis method, timing and choice of outcome methods and sample size. These are performed by the whole group, but led by the statistics.

Objectives are important to agree in detail as early as possible, particularly in later phase studies, and must be in a form that can be tested statistically.

Study design may be dictated by these objectives, but there are other elements that need to be considered (eg, blinded, parallel or crossover etc.) Methods must be carefully chosen to avoid bias; however these are not always possible in the real world, due to practical or ethical constraints. Compromises may need to be made to make the study achieveable, and this may require careful negotiation.

Selection of endpoints is largely a clinical decision, but statisticians can advise on freedom from bias and ease of analysis. This can also impact on sample size. Again, compromise might be required.

Analysis methods are mostly left to the statistician, but clinical input is still essential, as different analyses might be possible, and they might provide subtly different clinical information. Examples include repeated measures vs endpoint analysis, number of adverse events vs number of patients with events etc.

Again, even in sample size, many other non-statistical inputs are required, some of which might be subjective! This includes consideration of a ‘clinically relevant difference’, which has a significant impact on the sample size and needs to be discussed more widely. Sample sizes can be significantly more than imagined by non-statistians, which can raise budgetary issues.

Adam moved on to consider protocols from his perspective as an ethics committee statistician. He highlighted the importance of completing the ethics application form correctly, so it gives the committee the information it needs to review the study. The application form is the primary document, rather than the protocol, so don’t assume that the protocol will be read. Also, the committee contains lay members, so the application needs to explain some concepts in more detail than might be expected for medics alone.

When reviewing a protocol, Adam made particular mention of the sample size: too large is unethical (but rare, because of cost), and too small is also unethical as the study won’t answer the question! The committee needs to decide that the balance between risks and benefits involved with the study is acceptable. This depends on the scientific validity of the study.

Other common problems his ethics committee sees include: poorly written patient information sheets (in as much as 50% of cases!) including careful description of risky or unpleasant procedures, poorly explained methods, and inconsistencies in the application and between the application and the protocol.

In response to a question, Adam agreed that patient information sheets are getting longer. Certain elements are required by ICH GCP and templates are available from the NRES website. Adam suggested that a study summary would enable the patient to decide whether to read a more detailed subsequent description. However, some studies fall outside ICH GCP (eg, of a registered drug within its indication) a simpler approach would be beneficial.

Another question mentioned adaptive trials. Adam said that expert advice is a pre-requisite, but also suggested that checking assumptions of sample size midway through the study can be beneficial. This can be tested without breaking the blind, and Adam suggested we do this on any ongoing study; increasing the sample size mid-study could avoid a study failing to show a conclusive result.

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Pharma view on trial protocols

Posted by Andrew Smith on February 24, 2009

Sandra Waechter, Senior Project Manager with Janssen-Cilag, gave the pharma view of protocols. She outlined the overall process for developing a protocol, moving from global and regional product strategies, through research concepts and development plans, down to the level of individual study protocols. The development plan contains input from various stakeholders (eg, medical, regulatory, health economics etc.) on registration requirements, how to develop an indication, line extension etc. From this, it can be decided what studies are necessary to close any knowledge gaps.

A research concept is developed to plug a knowledge gap. This is sometimes developed with or without a specialist medical writer, but always includes primary and secondary objectives, scientific rationale, dosage, population, statistical plan etc. This concept is then reviewed and approved within the company to ensure that any potential safety and efficacy concerns are assessed. This is a global review, which can be complex due to the range of stakeholders and the need to align with global straetgy.

From this stage, the protocol itself is developed. Medical writers are always involved from this stage. A physician is responsible for the study, to discuss key features with key stakeholders (within and outside the organisation), prepare the synopsis and then forward it to the medical writer for further development. This is done using a standard template, based on the concept, timeline and event schedule. Sections are assigned to other specialists to manage delivery of, eg, the statistics section. It’s important to meet appropriate pharmacovigilance requirements, and that consistent terminology, structure and content are used, as inconsistency can trigger queries or imperfect implementation by site investigators. The medical writer then distributes the draft protocol to team members (including local operations teams) for review, specifying timelines for response.

Comments should be consolidated and reviewed, with the medical writer arbitrating changes if necessary. Moving on, the medical writer prepares and circulates the final draft. This needs to go for broader approval by global company stakeholders, including statisticians, medics, lawyers etc. After any changes, the final protocol is finalised and signed off.

Sandra shared her company’s definition of protocol revisions vs amendments: basically, whether it has been distributed to competent authorities, ethics etc prior to the change request arising. Any revisions or amendments need to be reviewed in a similar way as before. Again, Sandra highlighted the importance of version control throughout this process.

Sandra then spoke about her role as a project manager. She assembles the protocol team, covering all relevant areas of knowledge, defining tasks and setting timelines and lines of communication. She manages the development process, developing a budget, creating a realistic milestone timetable and ensuring appropriate quality processes are followed and ultimately tracking progress and driving execution to time and budget.

She outlined her expectations of medical writers: to develop a deliberated and well-written protocol that clearly addresses the describes the research question and study objective. The introduction is vital, which must be up to date with current literature, positioning the research question in this context with correct citations. The protocol must contain enough detail to enable investigators to conduct the study, including consistency in wording. The medical writer should be pro-active in approaching stakeholders to collect information, organise copies of all study related materials to be included in the appendices before submission, and ensure that the document complies with any relevant regulations and guidelines.

In response to a question, Sandra said that the whole process should take around 3 months.

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ICR/EMWA conference on trial protocols

Posted by Andrew Smith on February 24, 2009

This morning, I’m live-blogging from the ICR/EMWA joint symposium on collaboration in developing clinical trial protocols. This meeting will be reported in a future issue of CRfocus and The Write Stuff, with the afternoon session reported by Alexandra Dedman.

Wendy Kingdom opened the meeting and then handed over to Debbie Reynolds, Senior Medical Writer at Dianthus Medical. She discussed the details and diplomacy involved in writing a study protocol from the perspective of a medical writer.

She described the people involved in the process: medical writer, statistician, investigator (internal and/or external), sponsor representative and hopefully a monitor to advise on the practicality of the process.

Speaking as a medical writer, Debbie highlighted that they are specialists in putting together complex documents, getting input from other experts, and devising the protocol with the eventual study report in mind, making it easy to understand and to implement. She put the medical writer’s role in the centre in terms of diplomacy to resolve disagreements between other contributors.

Debbie then went on to discuss some of the common problems. These included agreeing a detailed synopsis, coordinating the team, resolving disagreements (eg, power vs cost), meeting all the requirements of sponsor, investigator etc., coordinating comments and version control between the multiple other contributors.

She then discussed examples of how it can all go wrong, such as a team member missing a deadline, with knock-on time issues, team members changing their minds, confusion of differing versions etc.

Suggesting how the process could be improved, Debbie suggested using a specialist medical writer, agree on a detailed synopsis, put somebody in charge of coordination, be strict on version control and deadlines, and finally to trust the medical writer’s skills.

Bringing her presentation to a close, Debbie discussed the CDISC protocol standard to enable machine-readable protocols, using XML to tag data fields in a structure. This makes it easier to generate CRFs and study databases (and, of course, a human readable version). Other advantages include that each data field is used only once, so a single change can be flowed through the whole of the document, rather than needing to make the same change multiple times.

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