Vacation Photos

I've just returned from a restful vacation in Vienna and Budapest.  I posted some photos here to share.

Budapest, Hungary

Schönbrunn Palace

Vienna, Austria

I'm planning a few more clinical research related blog posts before the end of the year.  This has been an extremely rewarding year at work and we have been celebrating a handful of accomplishments this month.  January promises to be the start of another busy year!

Happy Thanksgiving

Today I am thankful for time with my family and my little dogs.  I am also extremely thankful for another rewarding and challenging year at work. I love my job and the team I work with make every day in the office interesting and fun.  Their reliability and focus on quality are unparalleled in any of my previous positions and I truly feel at home with the group so I am hopeful for all of our continued success in 2013.  I've been in my current position for a year and today I am filling out my self-assessment performance review (and eating turkey!); I can happily report that our team exceeded many of our objectives.  Hip hip hooray, perhaps I will take the rest of the year off as a reward. ;)

Reflecting back, I regret that I didn't post some of the draft posts I wrote for this blog and that I have yet to share some of the interesting Q&A correspondence I have received through leadcra-mail@yahoo.com.  I did, however, correspond with many of the blog readers via email, helped launch the careers of two clinical trial assistants, coached an old (and awesome!) co-worker in the Pharmatimes Clinical Researcher of the year competition, and accepted a second invitation to speak at an upcoming clinical trials conference.

I feel very rich and blessed from the connections and networking I have made through this blog. There are still a mix of interesting topics and experiences I would like to share with you all.  Please trust that some new blog content is in the queue and I plan to get back to it post haste (pun intended).  Please keep the comments and emails coming as your feedback makes this project so much more fulfilling.  Thank you again for your continued readership and support.  Happy Thanksgiving!

You may also like...from The Lead CRA archives:

• Today in History October 2011
• What Makes a Good CTA? February 2011
• Dealing with Poor Performance Feedback April 2010
• How I Got Here January 2009

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.

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.

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!



You may also like...from The Lead CRA archives:

• Investigative Site Recruitment Plans September 2010
• Selecting Qualified Investigators April 2010
• Close-Out Visits March 2008

Tips for Better Monitoring Visits

These are four tips for great monitoring visits.  It all comes back to developing solid relationships as a site manager so you will have access, cooperation, and enjoy more productivity during your time on site.

1. Effective Communication Between Visits

Maybe your coordinators truly are
time-strapped or maybe they just
need a little cheerleading. 

Great communicators know that strong relationships are built on 2 parts listening/respecting and 1 part actively addressing concerns and providing solutions.   Follow-up with your sites weekly to track enrollment, discuss supplies, answer questions, and track EDC completion.  If things aren't trending consistently with your other sites work to uncover the root cause.  During your calls remind the staff of important study updates, upcoming data deadlines, or recent correspondence.  This is especially important with complex protocols.  Keep the check-ins positive, praise often, and be respectful of your site's time.  Communication is a two-way street and hopefully your sites will be comfortable to reach out to you as well.  If you are providing value to your site, they will be more likely to call you when they have questions or concerns rather than proceeding to make errors in execution that you may not discover until your next visit.

2. Assess Site Skill Level
The worst thing you can do is show up to a site and tell them how to run the study.  Don't discount the experience of the investigator/staff. When you go in like a hall-monitor and immediately criticize their process, they will stop listening, become defensive, and you will not be able to compel them to review or revise. First see and appreciate how they are organized, what source are they using, where are they losing efficiencies, and where could they be more precise.  Your first visit should be more than 75% observation and checking things out and less than 25% training unless they are asking for more.  Remember that you can train after the visit during your follow-up phone contacts.  You will need to tailor your site management approach depending on the experience and comfort level of your site.

3. Prepare for the Visit
From your home office or at least a week in advance of your monitoring visit, read the past report, review that pending action items are resolved, and ensure your study coordinator and other relevant site staff will have adequate time for the visit (if not, consider rescheduling). Know the enrollment rate for this site and other sites in the trial.  Compare the performance of this site with other sites and review all the EDC queries and responses since your last visit.  Communicate the agenda prior to the visit.  If you prepare properly for the visit, you'll reduce the risk of a non-productive visit and also be ready to handle any surprises you might discover on-site.

4. Demonstrate Flexibility
Sure you have an agenda and you can't possibly leave the site for the airport until you've achieved all of your objectives, but be willing to shift your day around to accommodate your busy coordinator.  You can perform your monitoring tasks in a different order if that helps the coordinator get organized and juggle your visit while still attending to other priorities.  Agree to do drug accountability while your coordinator wraps up a few outstanding queries in a patient chart.  Agree to meet with the PI at mid-day since they have clinic visits all morning.  The staff at the site will appreciate your flexibility.


You may also like...from The Lead CRA archives:

• Motivating Your Study Coordinators February 2011
• What is up with this coordinator? November 2010
• Routine Monitoring Visits March 2008

Lead CRA Q&A: Do We Have To Do an SIV?

Melissa commented in... "Pre-Study Visits and Site Initiation Visits":
Do sites HAVE to have an SIV? Especially for a simple data collection study? Or is a web training sufficient for sites that have done research with us before?  -September 9, 2011

NadiaBoBadia responds...

Hi Melissa, it sounds like you may be working on a non-interventional observational study (so no medication or any special assessments or survey instruments are given. For your study, perhaps you are just reviewing standard data that would be collected in the course of normal clinical conduct). In that instance, you may be able to do a web training for sites that you know and have worked with recently.

Without an in-person visit, however, how will you be sure that the facility remains adequate and that the study can be conducted there feasibly? As sponsors, we are obligated to ensure that the people working on our studies are qualified by education and experience. You could do that remotely by reviewing CVs and monitor reports for other studies. I hope this addresses your question. certainly there is a trend to not have expensive Investigator Meetings and I have worked on many studies where the PSV is combined with an SIV.

 It is important to visit a clinical study
site to inspect the labs, pharmacies,
facilities, storage, and other areas
where the research will be conducted
to ensure they are adequate.

It is more rare for me though to work on a study where there is no SIV at all but this sometimes happens when it is a site that we have had recent experience with (say in the past year).  We sometimes also waive the SIV when the PI and the important study staff attend the IM. If you won't be performing SIVs, definitely document at the sponsor level TMF how you determined the sites were qualified and trained.

Reader questions may have been edited for spelling or grammar, for reasons of anonymity, truncated, or edited in other ways although the main content remains unchanged.

You may also like...from The Lead CRA archives:

• Selecting Qualified Investigators April 2010
• Routine Monitoring Visits March 2008
• Close-Out Visits July 2008

ACRP 2012 Global Conference in Houston, TX

I received a mailer the other day with program details for the ACRP 2012 Global Conference.  I am on the ACRP mailing list but I have never attended the conference before.  This year it is being held in TX April 14-17.  There are a handful of sessions I would be interested in and I think the networking and vendor showcase could be worthwhile.  The conference has content for monitors and program managers but also content geared towards study coordinators and site directors.

Here is a link for more information on the conference if any of you are interested in attending:

http://www.acrp2012.org/acrp2012/public/enter.aspx

Who is heading to Texas for ACRP Global
Conference in April?  Blackberry and Brisket...
who could ask for anything more!

If you have been to the conference before I'd love to hear if it was fun and useful.  You can leave a comment here or shoot me an email at leadcra-mail@yahoo.com.

Lead CRA Q&A: Consenting Subjects Before IMP is On-site

Anonymous commented in... "Pre-Study Visits and Site Initiation Visits":
Post SIV, can a site share the Informed Consent Form (ICF) with pre-identified subjects prior to Investigational Medicinal Product (IMP) receipt at the site? -November 26, 2010


NadiaBoBadia responds...

Hi and thanks for your question. In one of my previous trials, all of our sites consented and screened subjects prior to receipt of Investigational Product. First shipment was only triggered after a second qualifying screening visit (4 week screening window with up to 40% screen failure rate).

Investigational Medicinal Product can only
be released to a site once all of the required
regulatory paperwork is in place.

In order to consent, our SOP required that the site be authorized for drug shipment, rather than requiring that drug was actually physically on site. In order to authorize drug shipment the site must have 1) completed the SIV 2) received IRB approval for protocol, ICF, Investigator's Brochure (IB), and all PRO instruments 3) Submitted complete regulatory document package to sponsor (1572, signed/dated w/i 1 year CVs for all personnel on 1572, Financial disclosures, Protocol signature page, IB signature page, etc. (some of this package goes to the FDA before the trial is initiated at the site) 4) fully executed contract and budget 5) written activation letter from sponsor. At that point the sites were allowed to begin distributing ICFs for review and signature.

Reader questions may have been edited for spelling or grammar, for reasons of anonymity, truncated, or edited in other ways although the main content remains unchanged.

You may also like...from The Lead CRA archives:

• Selecting Qualified Investigators April 2010
• Routine Monitoring Visits March 2008
• Close-Out Visits July 2008