Taking Control of the Process
A Whitepaper and Workshop by Nancy J Stark, PhD
Wednesday, 21 July 2010, 11 AM Central; or OnDemand soon after.
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You can only expect what you inspect
As a manager, you know its true. As a monitor, you know its true. A clinical study can be doomed from the start due to poor design, or it can evaporate into a cloud of non-enrollment and no data without watchful nurturing while it matures.
Recently a couple of clients asked me to review their protocols after they had IRB approval. Here are some of the problems I found: the least trained people were recording critical data (patients and home-healthcare providers); subjects received permanent implants with no provision for long-term follow-up; no provisions for documenting patients who were screened but not enrolled; and big-name investigators who only did difficult cases, not the everyday cases required by the study. All of these design problems are fixable, but it's embarrassing, time-consuming, and expensive in lost opportunity costs, to go back to the IRB for changes.
Plans are useless, but planning is essential [Eisenhower]
Everyone manages projects, whether you're planning a trip to China or changing the spark plugs. You know its a project if it has a beginning, middle, and end. You are managing the project if you take specific, planned steps on a defined schedule and within limited costs to achieve a distinct, pre-determined goal.The six steps of project management are as old as the hills and as familiar as a summer day; but it isn't always obvious how to apply the steps to clinical trials.
... Define the clinical project
The first step is to define the project. Why are you conducting the study? Is it an early developmental (feasibility, first-in-man, proof-of-concept) study? Is it to gain 510k or PMA or other regulatory approval? Is it to add a new indication for use? Is it a post-approval study to gain visibility, exposure, or additional clinical history? Is it to show non-inferiority to your biggest competitor?
I insist that my project development team request a clinical trial in writing, and that they answer the following questions:  what is the device being tested,  what is the business objective of the product development project,  who is the target market, i.e. who makes the buying decision,  what are the intended use and indications for use,  what are the features, functions, benefits, or outcomes you hope to make claims about, and  who are the major competitors, including competitive procedures.
Tricky me, I have just gotten the team to design the clinical study for me: number one is the device being studied, two tells me if I should look for a big-name or a first-time investigator, three tells me the medical profession of the investigator, four identifies the subject population, five describes the primary endpoints, and six tells me who or what to use as a comparator.
Do You Need A Clinical Research Quality Management System?
CDG's Clinical Research Quality Management System is a comprehensive collection of statements, policies, procedures, templates, and supporting documents that contains everything you need to set up a clinical research function.
Each procedure is designed to tell you 'how to' do something and results in a work product such as a document or report. The procedures are organized chronologically, the way you would organize a project schedule, to walk you step-by-step through the process of running a clinical trial and a clinical department.The manual is divided in sections that follow the major activities of a clinical project. For more information click here.
... Clinical project schedules
Next comes the task list and Gantt chart. You make a list of every task to be done. If you're a "lumper" you might see a clinical trial as five easy steps, if you're a "splitter" you might see it as several hundred. I cannot wrap my mind around more than 20-30 tasks, so I prefer to work with tasks and sub-tasks in order to keep things manageable. You want to have enough tasks so the project team understands what comes next, but not so much as to confuse them.
Then you organize the tasks in chronological order. Some tasks will overlap in time, others will be in sequence. For other tasks, what is important is that they end at the same time. I have never thought of a good clinical study example for this, but think of your supper tonight. You hope the chef will have the meat and potatoes done at the same time.
Next you estimate how long it will take to do each task. Writing a new protocol without a prior example to work from takes about 30 working days. Designing the content and layout for case report forms takes about four hours per page. You should look backwards into your company's history to get numbers that are realistic for your product area.
Finally, you link the tasks to make a Gantt chart. The most popular application for this is Microsoft Project, but there are other affordable applications as well. Gantt charts really are important: without them the team doesn't understand why even simple trials on non-significant risk devices take an average of six months from conception to first product on first subject.
... Resource allocation
Subjects, investigators, and monitors are the three most important human resources to allocate. The statistician will tell you how many subjects are required and the protocol will dictate the number of case report form pages that will be generated and over what time frame. Using that information you can estimate the number of investigators (investigative sites) you'll need and the number of monitoring hours and monitors you'll need. The fewer the better.
You may need to allocate some physical resources, too. One company I worked for required the clinical research function to order and 'buy' investigational devices from the manufacturing function. The financial department actually moved money from one function's budget to another.
...  Clinical project estimates, why do studies cost so much?
For each task item you'll assign a cost. The cost may be fixed (such as a one-time IRB fee), per unit of work-hour (such as internal or contracted labor), or per unit of material (such as forms or devices.) The most accurate way to do a budget is to look at the actual costs for a similar study and add 5%, but you'll need to do a zero-based budget if you don't have a past one to work from.
As much as 50% of the entire budget may be spent before the first device goes on the first subject! A task-related (line item) budget really is important. It communicates to the the team and to management where the money will go, and why so much will be spent before there is any data. As a clinical researcher, you should talk about this a lot—keep it in front of the team's face—get them used to the idea of spending money first in order to get good data later.
... Site support, study management, and reporting
During the implementation process is when most studies fail. Once study start-up is completed there is a tendency to coast while the site does the work. Keep active contact with the site with emails or phone calls every week, a good study coordinator both expects this and appreciates the attention. Provide the site with updates on the trial as a whole, everyone is part of the team and needs to be included.
Study management means following the events and progress of a study; adding or moving resources as needed to get the job done; advising, coaching, or even intervening if personnel are floundering.
Reporting means making certain that top management, other sites, and regulatory authorities are informed as required.
... Study close-out
Finally the fun—a celebration for study completion. But some work, too, as you assure the site is inspection ready. Study close-out is like doing your income taxes. If you have done a good job of record-keeping all study long the close-out process will be simple. If you have been careless in ongoing record-keeping the close-out process can be expensive and complex.
If you liked the whitepaper, take the workshop
The objective of the workshop is to learn how to plan and manage a clinical study. Sign up at registration.
You will receive, we will discuss
[x] PowerPoint slides.
[x] A 4-5 hour presentation.
[x] How to craft a Clinical Development Plan.
[x] How to craft a Gantt chart.
[x] How to calculate monitoring time (labor).
[x] How to estimate the number of monitors needed.
[x] How to prepare a clinical study budget.
[x] How to estimate the cost-at-completion midway through a study.
[x] A checklist of documents to be retained in the sponsor's study file.
[x] A 30-minute quiz to reinforce your learning experience.
[x] CEUs and certificate of attendance.
Who should attend
[x] Clinical research professionals who want to improve their study management skills.
[x] Clinical research managers who need better planning and reporting from their group.
[x] CROs who want to improve their proposal skills.
[x] Executives who are planning the future of their company.
Dr. Nancy J Stark is President and Founder of Clinical Device Group, a CRO and consulting firm that has been in business since 1990. Her curriculum vitae can be found at www.nancystark.com.
[x] Personal computer.
[x] Internet Access.
Date, time, registration
The 4-5 hour workshop will be presented on Wednesday, 21 July 2010, at 11:00 Central Time. Event materials will be distributed the day before the workshop. Sign up at registration.
Nancy J Stark, PhD
President, Clinical Device Group Inc