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Monday, April 16, 2012

Site Startup Series

Welcome to The Lead CRA Blog Site Startup Series.  This course of blog posts is designed to step you through the various activities of launching a clinical trial site.


What are the regulatory requirements before recruitment can begin? What are typical sponsor requirements? How do clinical trial sites even get chosen? These topics and more, demystified in the series below:
  • What are the typical milestones of site startup?
  • Metrics, trackers, reports, and dashboards
  • What is feasibility? How do sponsors choose which clinical trial sites they work with?
  • What is an essential document package and a regulatory submission?
  • Informed Consent Form templates
  • Why do contracts take so long? How are they complicated?
  • Site Budgets
  • IRB submissions
  • Calculating Investigational Product needs
  • Providing study supplies and source documents
  • Ensuring sites are adequately trained and prepared to participate
  • Developing Investigative Site Patient Recruitment Plans
  • What correspondence goes in the Trial Master File?
  • Gating tasks...bottlenecks
  • Lessons learned, where did the process breakdown?
  • How to speed up site startup?
Are there other questions or topics that you would like me to cover related to site startup? Please leave me a comment or drop me an email at leadcra-mail@yahoo.com.

Sunday, April 15, 2012

Thinking About Site Startup

I've been thinking a lot lately about how important it is to choose the right clinical trial sites for the success of your trial.  Just last week I blogged about the painful process and high costs of closing non-performing or under-performing sites.  I recently told a non-industry friend that it can take upwards of 18 months sometimes to usher a clinical site from selection to initiation.  He responded, "well that make sense since many clinical trials last several years and it takes a while to give the medication to enough patients to test it out thoroughly."  Then I realized he had misunderstood me, I clarified, "Initiation means the doors are open. At initiation, a doctor can start looking for patients.  I am telling you that it can take one year or more sometimes just to get a site open for recruitment to start the trial."  He was floored and responded, "no wonder we're paying so much for our prescriptions..."

I recently went to an ACRP seminar called 'Why Sites Fail in Study Startup'.  The dynamic speaker, Christine Pierre is the President of RxTrials Institute (RxTi) and gave a terrific talk.  If you would like to meet her or discuss this topic further, perhaps you would like to attend the Site Solutions Summit in October.  I haven't booked my travel yet but I am definitely considering going.

Early bird rates are available now!
I am excited to see the next-generatiion startup
tracker product when it is released. 
Then, a few days ago I traveled to downtown San Francisco, CA to visit the offices of goBalto. This innovative company has developed a web-based platform for Clinical Study Startup, Tracker™. The software "enables clinical trials sponsors to collaborate with multiple partners directly from the web in a transparent and regulatory compliant manner".  They invited me to a demo of their next generation product to participate in a user feedback session.  I was really impressed and found them to be extremely forward-thinking.  I am excited to see the product when it is released.

So, all of this has led me to develop a new series for the blog focusing on: Site Startup.  In addition to my work as a Lead CRA, I have been involved in clinical study site startup for a variety of pharmaceutical companies pretty much without interruption for the past 28 months.  Whoa, over 2 years you say?  "Surely, Nadia you must have tremendous experience launching study sites for many clinical trials in that time!"  Yeah, well uh, regrettably, no.  However, in that time I have worked with six disparate clinical operations teams and supported the process of opening a few hundred sites in five different countries (mostly Phase II trial sites).

As a regional monitor at a CRO, I would routinely assist with pre-study site selection visits and administration of feasibility questionnaires but the majority of my work was 85% regional monitoring and site management once sites were open.  Since I have moved to an in-house role, I spend a lot more time in the start-up side of things, buried in spreadsheets, trackers, dashboards, and demands from my boss and the board of directors, so I have gleaned some valuable insights. We'll be stepping through several broad topics of site startup in the coming weeks including:
  • What are the typical milestones of site startup?
  • What is feasibility? How do sponsors choose which clinical trial sites they work with?
  • What is an essential document package and a regulatory submission?
  • Informed Consent Form templates
  • Site Budgets
  • Why do contracts take so long? How are they complicated?
  • Developing Investigative Site Patient Recruitment Plans
  • IRB submissions
  • Calculating Investigational Product needs
  • Providing study supplies and source documents
  • Ensuring sites are adequately trained and prepared to participate
  • What correspondence goes in the Trial Master File?
  • Metrics, trackers, reports, and dashboards 
  • Gating tasks...bottlenecks
  • Lessons learned, where did the process breakdown?
  • How to speed up site startup?
What is missing from this list? Do you have other questions or topics that you would like me to cover related to site startup? Please leave me a comment or drop me an email at leadcra-mail@yahoo.com.

Monday, April 9, 2012

Closing Non-Performing Sites

According to a 2009 study by Morrison and Pfizer, roughly 30% of sites that are opened fail to enroll.  Despite careful site selection criteria and thorough feasibility, dud sites are opened in most trials (although unintentionally and we do go to great measures to avoid this). In my career I have only worked on three studies where every single site enrolled at least one patient.  It is more common to have a handful of sites that recruit the bulk of your patients and then between 10-20% of the sites who never randomize a subject (about 75% of these will offer you Screen Fail subjects...oh boy).

Non-performing sites are a drain on resources and will have a negative impact and cost to your study.

So let's talk costs of non-recruiting sites.  There is a huge expense to your timeline when a site fails to perform or under-performs because inevitably you are now spending more time to recruit and pick up the slack at other sites.  It is a large drain on resources to start and carry a non-performing site; you still have to monitor, supply this site, contact this site, train this site, perform budgeting and accruals for this site, and provide additional support and cheer-leading for a nonperforming site.  Almost assuredly, those tied-up resources would have a better return on investment if re-directed to other study activities or to support the sites that are making more significant contributions.  Finally there is an opportunity cost because you likely have selected this particular site in lieu of another site that may have been a better recruiter.

Since non-performing sites cost your study, it may be worthwhile to close them, even before the end of the trial. Cut your losses and limit your disappointment.  Your company may choose to close a site that has enrolled subjects but this is much more rare.  This is more likely to happen because of a change in PI, departure of qualified staff required to perform assessments, or some other irreconcilable issue.

Don't let one bad apple spoil the bunch...
Now, I am beating up on the non-performers so I will pause to say that sometimes sites don't perform and it is not anything that they can control.  Perhaps the inclusion exclusion criteria are too stringent, if they don't have access to the right patients, if a more attractive study is recruiting nearby, and so on.  However, for the purposes of this discussion, let's instead call out on some more avoidable reasons that sites fail to recruit: competitive trials at the study site (your PI is cheating on you!), failure to negotiate an appropriate budget, insufficient staffing and resources, no commitment to an Investigative Site Recruitment Plan, uncoordinated search through clinic charts or database, out-of-sight / out-of-mind, inexperience in "pitching" the trial to potential participants, inattention by the PI/failure to prioritize the trial, etc.

Many site contracts are written now so that a start-up fee is partially or wholly refundable to the sponsor if enrollment does not occur within a pre-defined timeframe.  As a cautionary tale, beware of the risk of losing goodwill at your "nice" sites when you close your "naughty" sites.  The community can be tight (and chatty) so conduct yourself accordingly, and exercise tact and professionalism.  If you tread carefully, you may be able to salvage the relationship and appoach this site for future feasibility (assuming you would even want to...past performance is usually the best indicator of future capabilities...).  As an added bonus, you will avoid the ripple effect of negative morale, concern, or fear at your other sites; these can be very de-motivating and halt/delay your study recruitment.

For more information on the tasks required to close a site please refer to a previous blog post on close-out visits.

Are there other hidden costs to keeping a non-performing site open? I would love to hear your comments or you can send me an email to leadcra-mail@yahoo.com - thanks!



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