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

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

Global competition

Multinational Trials: A New Balance Point?

Andrew Smith

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

Managing Clinical Research in the UK: Survey & Conference

Andrew Smith

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

Feature

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

Emily Scott

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

Prof. development

Study Management for Research Nurses: ICR Research Nurse Forum

Nicky Perry MICR

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

Virtual Learning in the Real World: ICR Tainers’ Forum

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

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

Trial technology

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

Elena Skryabina

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

Book review

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

Allan Gaw, reviewed by Andrew Smith

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

Regular update

Fit For the Future: Message from the Chair

Janette Benaddi MICR CSci

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

It’s Not All Work, Work, Work…

Compiled by Andrew Smith

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

CRfocus: Table of Contents of June 2009 issue

CRfocus 20(06) – June 2009

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

CRfocus: Table of Contents of May issue

This is the Table of Contents of Clinical Research focus 20(05) for May 2009. Members of The Institute of Clinical Research can click on the links to read the full text of each article.

Features

Strengthening Protection of Research Subjects: The 2008 Revision of the Declaration of Helsinki

John Poland FTOPRA

The Declaration of Helsinki was developed to underpin the ethical conduct of human clinical research. Eight years after its previous major update, which prompted two clarifications on contentious points, the Declaration was revised late in 2008 after a process lasting nearly 2 years. John Poland provides a detailed view of the latest revisions, which have provoked mixed responses from regulatory, ethics and clinical communities.

Lost in Translation? Challenges in Preparing Participant Information for Multilingual Studies

Nicky Dodsworth MICR CSci & Efraim Roe

An increasing number of studies are being performed in parts of the world whose first language is not English. There are challenges in translation and communicating science in a multilingual world dominated by the de facto language of English. Nicky and Efraim look at the issues surrounding translation of the patient information and informed consent forms.

People

A Career Championing UK Clinical Research: An Interview

Richard Tiner

Richard Tiner steps down as Medical Director of the Association of the British Pharmaceutical Industry (ABPI) at the end of May, after nearly 13 years in the post. Over that time, he has been a prominent speaker at ICR events, and was the first person we interviewed for CRfocus. As he prepares to move on, he reflects on the changes in the UK clinical trials landscape since the mid-1990s, in which he has been instrumental.

National update

Local & National Perspectives on Streamlining R&D: ICR Scottish Forum

Mary Mumford RICR

Mary reports on the October 2008 meeting of the ICR Scottish Forum. At the meeting, Dr Janet Messer, Deputy Director of the NHS R&D Forum, gave an overview of the initiatives to integrate and streamline R&D activities throughout the NHS, while Brian Rae, R&D Manager of the Greater Glasgow & Clyde NHS Trust, spoke about the successes and challenges in developing world-class clinical research structures in one of the most health-challenged regions of the UK.

Professional development

Spice Up Your Interview Technique

Shanoo Singh

Being interviewed can be a nightmare. Interviewing skills have been rapidly and continuously changing over the past decade. Having been both a candidate and an interviewer on many occasions, Shanoo reaches out to everyone, particularly those seeking their next strategic positions, and offers some tips on how to perform at your best in an interview situation.

Viewpoint

Always Compete on Value; Never on Cost

Andrew Smith

When the economic upturn comes, the individuals, organisations and indeed countries that will be best placed to succeed will be those that have continued developing through the lean times. As an industry, we’ve become very good at working costs out of our processes. However, focusing solely on this risks neglecting importance of creating additional value for companies, shareholders and society as a whole. The relative risk of trying to leap ahead through strategic innovation is actually lower now than in ‘boom’ years, those that innovate and survive will secure their place at the forefront of the industry for a generation.

Devices, Drugs, Directives & Directors

John Kolthammer HonFICR

To recognise that our new Chair of the ICR Board of Directors has a background in medical device development, John Kolthammer, former CEO of ICR, offers a respectful and somewhat light-hearted reminiscence to draw attention to the some of the interesting issues that have always been present at the interface between pharmaceuticals and medical devices.

Regular update

Uncertainty & Opportunity: Message from the Chair

Janette Benaddi MICR Csci

Janette inspires us to remain optimistic and look harder than we have ever done for opportunities, despite any current financial insecurities or media-fuelled gloom. To add personal despondency to this will surely reduce our individual ability to cope, and will probably also make the wider recession both longer and deeper. It’s challenging to look on the bright side, but she believes that there is a bright side for many of us, if we care to search for it.

It’s Not All Work, Work, Work…

Compiled by Andrew Smith

Our regular look at the lighter side of clinical research, including “Ten innovations that won’t add value to sponsors, shareholders or society” and engaging with patients in language that is a bit more “street”…

CRfocus: Table of Contents of March issue

Making up for the delay with February’s Table of Contents, here is the Table of Contents for the March issue of Clinical Research focus 20(03). Members of The Institute of Clinical Research can click on each link, and log in to read the full article. If you want to become a member of ICR, visit www.icr-global.org/membership for more information.

Patient recruitment & retention

Adjust the Focus on Recruitment & Retention: Enabling CRAs to Develop & Implement Site-Specific Plans

Sherry Armstrong-Wilkinson MICR

If you want recruitment and retention to succeed, then it’s time to adjust the focus on where investment is made. When selecting and training CRAs, how much time and investment do we put into developing skills and expertise that will allow them to support sites fully in the development of robust and strategic recruitment strategies? Sherry explains how a strong, dynamic relationship between investigators and CRAs is crucial for optimal site management and is vital for devising and implementing successful site-specific strategic recruitment and retention plans.

Exploring Patient Recruitment: NIHR Primary Care Research Recruitment Methods Group

Elaine Ward, Julia Miller & Brendan Delaney

As government policy is encouraging a larger number of patients to be seen by clinicians in the community, more clinical research studies require some recruitment in primary care. The Research Recruitment Methods Group came together in 2007 in a bid to begin to tackle recruitment barriers in primary care. Between them, the members of this collaborative group have had considerable experience of research conducted in general practice settings. Their aims are to improve delivery of clinical trials by exploring the factors which affect recruitment and then to develop a programme to systematically test the impacts of those factors. The authors discuss this group’s past, ongoing and future activities.

Factors Driving the Evolution of Digital Outreach for Patient Recruitment

Gaynor Anders, Mary Schwarz & Jake Perez

Most are aware that the role of digital media, particularly the internet, in recruiting patients for clinical trials has been steadily expanding in both availability and acceptance worldwide. But, what has driven the emergence of digital outreach for patient recruitment and where is it headed? The authors take a brief look at how we arrived at the present use of digital media in patient recruitment and look ahead to its future applications. They also consider the driving forces for both the past and future evolution of digital outreach for patient recruitment and the implications for the clinical trial landscape.

Planning for Success in Patient Recruitment: An Interview

Missy Orr

Missy Orr is Executive Director, Sites and Patients Services at PPD. Missy joined PPD in 2003 and oversees the global operations of patient recruitment activities. In this interview, we break down the component parts of patient recruitment, discuss why an approach might be successful in some places but not in others, and consider that patient retention doesn’t get the attention it deserves. An audio version of the complete interview is available to download.

Features

Real World Data: An Important Addition to Your Late Phase Development Plans

Samantha Marshall

Traditionally, ‘real world’ observational research has been criticized for lacking the robust scientific methodology of RCTs. However, with the shift in NHS requirements, the focus of clinical development needs to change to ensure a well-rounded development plan that includes not only RCTs but also more pragmatic research in real clinical practice. Samantha explores…

Health Technology Assessment in the UK & EU: NICE & EUnetHTA Conferences

Alan Jones

Alan gives us our regular update on the latest developments in Health Technology Assessment, how it impacts on reimbursement for the medicines and devices we help develop, and how its importance will only increase for people designing and conducting clinical trials. This extended version of the article includes more detail on both the NICE and EUnetHTA conferences than was possible in the printed version.

Viewpoint

Research Integrity vs Getting the Joke

Andrew Smith

Were ‘cellist’s scrotum’, ‘guitarist’s nipple’ and the PIGPEN study on the treatment of headlice simply a bit of light relief for overworked physicians, or dangerous distortions of the scientific record… or even disease mongering? Andrew eschews his usual humorous streak to suggest that unacknowledged hoaxes in primary medical journals might not be a great idea…

Regular update

So Long, Farewell, Auf Wiedersehen, Goodbye…: Message from the Chair

Susan Ollier MICR Csci

Susan Ollier, Chair of ICR until she reaches the end of her term of office at the Annual General Meeting on March 17th, looks over some of our recent achievements, thanks those who have made it all possible, and says a fond farewell to the colleagues and friends she has met along the way.

CRfocus on Twitter

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…

Panel discussion on development of clinical trial protocols

Following on from the last presentation of the morning session, the speakers came back to discuss the morning’s topics.

Initial discussion concerned lists and flowcharts to summarise what needs to be done and what data needs to be collected at which visit. Sue Mackay agreed that this would be useful, but some sponsors prefer to avoid duplication wherever possible. This is precisely the kind of thing that the CDISC standard discussed earlier would resolve.

A delegate followed up by asking what sort of aid site staff use to schedule visits and activities. This varies according to the type of study (eg, patient types, working hours etc.) but Sue Mackay said she tries to create a schedule as far as possible. Adam Jacobs said that including this in the protocol would be beneficial. Another delegate said that this could cause confusion over which document is the source document for GCP purposes. In many cases, patient notes are used; eCRFs are being increasingly used, although these can be restrictive if patients report additional information.

Another delegate raised the issue of global trials, where practical issues differ between regions. Sandra Waechter mentioned that some units make local protocol amendments to accomodate local differences in care.

Adam Jacobs discussed the pros and cons of detailed protocols vs broad protocols with more detailed appendices. One delegate questioned whether we could ever reach a ‘perfect’ protocol when it needed to meet the requirements of such a diverse set of stakeholders. Adam stressed the importance of having time to do the job properly: the situations in which his team have had problems have been when time pressure (eg, to meet an ethics deadline etc.) has been extreme. Although as little as 3 days is required to do the actual writing of the protocol, he agreed with the earlier speaker that 3 months would be an appropriate period to allow for the discussion, reviewing and negotiation processes.

Sue Mackay on the study nurse view of trial protocols

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.

Adam Jacobs on statisticians in protocol development

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.

Pharma view on trial protocols

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.

ICR/EMWA conference on trial protocols

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.