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

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

Today in History (and TheLeadCRA.com blog traffic statistics)

On October 12th:

• 1792 – the first celebration of Columbus Day commemorated the 300th anniversary of Columbus' landing in the Caribbean in 1492.

12-Oct-1999: A teacup yorkshire terrier
named George (the author's favorite artist
from the band The Beatles) is born.

• 1850 – The 1st women's medical school, the Women's Medical College of Pennsylvania, opens.
• 1928 – An iron lung respirator is used for the first time at Children's Hospital in Boston.
• 1968 – The music single "Hey Jude" by The Beatles tops the charts.
• 1976 – The People's Republic of China announces that Hua Guofeng is the successor to the late Mao Zedong as chairman of Communist Party of China.
• 1997 – John Denver, American singer dies at the age of 52 in a private plane crash.
• 1999 – Sir. George Basil, a teacup yorkshire terrier is the only survivor in a litter of five (and subsequently adopted by this blog's author).
• 2010 – Returning via airplane to San Francisco with her boss after nine Site Initiation Visits in less than eight weeks, the blog author, NadiaBoBadia is offered (and accepts) a free upgrade to the First class cabin. Remarkably, NadiaBoBadia is still regularly teased by her co-workers for not agreeing to surrender the upgrade to her supervisor. 

12-Oct-2010: NadiaBoBadia enjoys a complimentary fruit and cheese plate,
watches some TV in her comfy First class seat, and sends a
free glass of wine back to her boss who has to ride in Coach.

12-Oct-2007: 
The Inception of The Lead CRA blog

Oh yes, and I almost forgot to mention that on October 12th, 2007 after 1.5 years working as an in-house CRA, I received an employment offer to become a Regional CRA and I launched "The Lead CRA" blog.  I have really enjoyed sharing my experiences these past few years and I am more committed than ever to maintaining and updated the blog.  

Today I am pausing to give a special thank you to my loyal readers; to both of you, thanks so much! ;)  I've made many new connections with other clinical research professionals, some virtual and some in-person, all priceless to me.

A Snapshot of Blog Activity to Date

Actually, the blog traffic has increased to the point that I have purchased my own domain, a server cloud, and considered relocating to Wordpress.  All that and the entire blog is still relatively small with less than 100 posts and pages published since inception.  Just in the past 12 months, LeadCRA.blogspot.com has welcomed 10,000 visitors (65% of the readers arrive via a search engine, 20% of the readers are subscribed or come directly through links, email, or referring sites).  Roughly 40% of my visitors are repeat visitors so I continue to strive to provide content that keeps you interested and encourages you to return.  

Google Analytics tells me visitors have arrived at leadcra.blogspot..com from 3700+
cities representing108 unique countries. I am surprised to discover that the content
has been translated into nearly 80 languages other than English. Wow!
(North America-54%; South Asia-11%, East Asia-7%; Western Europe-7%; SE Asia-4%...) 

These statistics may seem pretty pedestrian for any of the fellow geeks in the crowd, but because the content I write is very focused, specific, and niche, I'm really quite thrilled with the turnout.  I am grateful to have the opportunity to continue to author relevant and (hopefully) interesting blog posts.  Your comments and emails definitely keep me going, so let's continue to stay in touch.  I have ~200 all-time comments - thanks!

Since last Fall, I've received 75+ personal emails with feedback, suggestions, career advice/resume questions, and a variety of other reader-recommended topics.  You can read through the archives here. Thank you for your patience when I don't respond to email straight away; remember this blog is my hobby and not my day job.  Despite the fact that I still only update the blog just once or twice a month, the project continues to be fun and rewarding.  

What's Next?
I have some exciting new content planned for the blog and I am always open to ideas for new topics.  I'd like to see some of the content I have developed get published in a professional journal, referenced in other industry websites, or disseminated through other social channels.  Therefore, I am working on several of these efforts in parallel this Fall.  I hope you will continue to check-in (please accept a free subscription by clicking this link if you have not already done so) and I always encourage you to share LeadCRA.blogspot.com URL with other Clinical Research Professionals so that we can maintain and grow readership.

Thank you once again for following along!

Efficiency Tips: Spend less time on your Timesheet

I am employed by a service company and we bill our clients for our services. Therefore, we must track our time spent on sponsor related work and pass the costs through appropriately. I am asked to track my time in 15 minute increments so I can basically report up to 4 time categories per hour or I can bill a half or whole hour to a specific time code. In order to receive a good performance rating, I must report at least 85% of my 40 hr work week as "billable time".

My non-billable time codes are things like: Sick, Holiday, General and Administrative Duties (G&A), Internal training (not project specific), goofing off (ok, so that is not a category but if ever I am shy of 40 hrs and can't account for the time then G&A is a good catch all), etc.

Billable time is coded by project (since I might work for several sponsors/projects at once) and then broken down into time categories as follows:
Project Specific Training / Sponsor Teleconferences - Reading protocols, watching power points, reviewing the Monitoring Plan, etc.
Preparing and Following Up - This category is used for making travel arrangements or writing confirmation/follow-up letters, or working on reports.
Traveling - Usually your project will have limits to how much travel time you are allowed to pass through. At my company, when long trips are unavoidable, you can lower your travel time by using the time in transit to complete other project related work such as studying or writing reports (billable to either of the 2 categories listed above) - obviously this works when on an airplane or delayed and not necessarily when driving!
Managing Sites - This is phone or email contacts to your study sites or running special project specific reports.
Conducting a Monitoring Visit - Actual time spent on site during SIV, COV, or routine MV.
Query/Database Management - Helping the site solve/close queries raised by data management, reviewing the clinical database, running reports, etc.
Expense Reporting - see my next post!

OK, so now that I explained how I categorize time, let me explain the time tracking system. You can think of it as a glorified version of Excel that lives on a web server. So to enter my time, I have to log into that system and enter all of my hours. We are asked to do this at the end of every day so we are as accurate as possible. Well, I don't have internet access all the time so sometimes I let a few days pass and it really is hard to remember what you did for the past 48-72 hours by 15 minute increments. To solve this conundrum, I made a copy of the fancy web-based timesheet template in Excel and I just leave it on my desktop. Each day before I log out of work, I update my time in my Excel template. Then every 2 weeks (or as I have time) I log into the web-based system and transfer it all. I know this is multiple steps but it seems to work better for me. You could also use a journal or jot notes about how you spent your time in your day planner. Any other tips?

Pre-Study Visits and Site Initiation Visits

Depending on the company you work for and the Standard Operating Procedures (SOPs), you may be required to complete an in-person Pre-Study Visit (PSV) before an investigator is initiated to join a clinical trial. In some cases, you may even be able to perform this via telephone, web-conference, or it might be waived altogether (say, for example, an investigator your firm has collaborated with in the past 18 mos or so).

The objectives of a pre-study visit are to review the adequacy of the site, the training and experience of the study staff, the access to the right patient population, and the site's interest in the study. If the site isn't motivated or if they are already participating in studies that would compete for the patient pool, they may not be a good recruiter. It is expensive to start up a site, monitor them, and supply them with all the study materials and training. Ideally, you would only open sites that would perform well but in reality, there are always 'dud' sites in every study (Read my related post on Selecting Qualified Investigators). This is typically a 2-4 hour visit. After your visit, you will likely need to complete a report template or assessment and send a follow-up letter to thank the site for hosting you and inform them whether or not they have been chosen to participate in the study.

At an Investigator Meeting there may be
presentations and break out sessions
to answer questions and train study
staff with the skills required to properly
execute the protocol.

The initiation of a site can sometimes occur at an Investigator Meeting (IM) where all the potential investigators are brought together in (a typically quite fancy) hotel or other conference arena to receive group training on the new study. More often, however, this will actually take place - on-site. This is usually a 4-8 hour visit and you may be accompanied by a Project Leader, Medical Monitor, or even Data Management personnel just depending on the desire of the sponsor. Before your visit, you will coordinate a convenient time for the study site and confirm your visit with a letter informing them when you will arrive and what the objectives of the visit will be. It is important to physically be at the site so, as a monitor, you can visit the labs, pharmacies, and other areas where the research will be conducted to ensure they are adequate. For example, both labs and pharmacies should have restricted access and the site should know where it will store the Investigational Medicine/Product (IP) and this location should be locked. If the site will be storing blood or tissue samples, you will inspect their freezers and ensure that they maintain adequate temperature logs and have standardized sample handling protocols and training.

During your initiation visit you will probably spend a great deal of time training or reviewing the study protocol design and answering questions from the site personnel. You will also want the Principal Investigator (PI) to be available for specific parts of your presentation. Specifically, you will need to discuss the Investigator's Responsibilities as related to the regulations to ensure there is agreement and understanding (The investigator may choose to delegate some of his/her responsibilities but ultimately, they will be responsible for all actions and conduct of the study. Specific study related activities can only be delegated to those who posses adequate training and experience -- a secretary cannot perform a Physical Exam, etc.); You will explain publication policies and documentation responsibilities; You will inform the PI that you will need timely access to subject's records and the acceptable time frame for completing patient data case report forms (CRFs) and answering queries regarding the data). Document everything that is discussed so you can add it to your report and if there are any questions that are unresolved at the end of your visit, you can include resolution for those in your follow-up letter after the visit.

Email me if you have more specific questions. Now that our study is underway, next time I will discuss how and why we complete routine monitoring visits throughout the study conduct period.



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

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

Introduction to Monitoring

I've been out on the road for the past few weeks assisting some other monitors to review patient's medical records and the data that has been collected for the clinical trial. It occurs to me, that it would be beneficial at this point to further describe to you the roles and expectations of a Clinical Research Associate (CRA).

In a pharmaceutical/biotech company, teams of scientists are working to discover new molecules, compounds, and foundations for new drugs. In addition, these same scientists sometimes work to re-formulate current drugs or apply them for new diseases and indications (all of this work is done in animal models before the human clinical trials can begin). It is at this point that monitors such as myself come into play. Once an experiment that involves humans is designed, monitors help the company choose qualified and interested physicians to carry out the study. These 'investigators' are reimbursed for their efforts to conduct the trial and a CRA may also help negotiate the budget and/or contract between the parties involved.

A CRA job is a traveling job. Sometimes we go to glamorous places but more often than not we are monitoring in hard to reach or otherwise obscure locations. 

Objectives when we visit the investigative site (Doctor office, hospital, research center, etc.) include: 1) perform pre-study tasks during a Pre-Study Visit (PSV), 2) kick-off the study with a Site Initiation Visit (SIV), 3) routinely check back with the site regarding subject enrollment, trial conduct, and data collection during one (or typically many!) Interim Site Monitoring Visits (MV), and finally 4) shut down the site after their participation has ended during a Close Out Visit (COV). Before and after each visit, there are a variety of tasks and communications that need to occur in regards to preparing for, scheduling, confirming, and then following up on items from previous visits. Read some of my other blog posts to learn more about Site Initiation Visits, Routine Monitoring Visits, and Close-Out Visits.

Also, between visits, a CRA needs to regularly contact the sites and perform site management activities such as answering questions regarding the study design, encouraging enrollment, sharing tips from other sites, and distributing study drug (Investigational Product, IP), and managing site supplies inventory levels (often you are assigned up to 10 different sites to manage but this really can vary depending on geography, how many patients/doctor sites are participating, how many monitors are on the study, how complex the trial is, and a variety of other factors).

I'll explain more regarding the key tasks at each visit in later articles. There are many Federal and International regulations that apply to human research to ensure that the studies are valid, reliable, and above all, that the rights of the participating subjects are protected and we'll also get into those soon.