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Wednesday, August 14, 2013

Let's All Move to the ClinOps Toolkit Now

The Lead CRA Blog is Moving to a New Home: ClinOps Toolkit

Thanks for visiting here, following along on Facebook and checking out the new blog project, ClinOps Toolkit.  Have you joined the Members only discussion Lead CRA group on LinkedIn?  It is especially for CRAs, private, and free. Join today!

Are You Subscribed to Posts Via Email?

If you have previously subscribed to my feedburner email service, I'll be sending you an invitation to opt-in to the free ClinOps Toolkit new subscription list.  Emails from the Lead CRA blog will not continue after August.  You can follow at the ClinOps Toolkit moving forward:

The Lead CRA archives and comments have already been ported to a new home at ClinOps Toolkit.  I will be redirecting all web traffic to the new site. If you have bookmarked any of the content here, your links may not work after August.

Thank you again for your support and continued readership over the years.  I look forward to continuing the exchange of conversation on the new blog, ClinOps Toolkit.
OK now, we're packed and ready to go. Let's all move to the ClinOps Toolkit!

Monday, July 15, 2013

The Lead CRA is Moving

I'm Relocating the Lead CRA Blog

If you are following along on Facebook then you probably already saw the announcement that I am moving the Lead CRA archived posts and as many comments as possible to my new blog project, ClinOps Toolkit. Don't worry, I want you to move with me.  Everyone is invited, let's go!

Please be Aware that Automated Emails Will Not Continue

If you have clicked follow or subscribed to my feedburner email list at some point in the past, then you may only hear from me a few more times via those services. I do plan to shut down the feedburner service in August in favor of a new free mailing list that offers enhanced templates and targeting so I can deliver the content that is better-tailored for you moving forward, but only if you opt-in to the new subscription list.

What do I Recommend For You? Re-subscribe.

If you would like to receive future posts via email you will need to sign up to the new subscription list that I created.  It is free, quick, and you can modify your preferences or unsubscribe at any time.

See You Soon in Our New Home!

As always, you can contact me via email if you have comments, suggestions, or ideas for future posts. I've got some ideas planned for August and you can follow along as my guest contributors and I publish new monitoring topics at the ClinOps Toolkit.

Much of the content here will be moved permanently to the enhanced blog and I will be redirecting web traffic to the new site. If you have bookmarked any of the content here, your links may not work after August.  Please be advised that I will redirect many of the links but some will likely become broken and inactive as I thin out the archives.

Thank you for your support and continued readership over the years.  I look forward to continuing the conversation on the new blog, ClinOps Toolkit.

Tuesday, June 25, 2013

Do you know a CRA Rockstar, a Super Study Coordinator, or an excellent PM?

Tell Them About the US Clinical Researcher of The Year Competition

The US Clinical Researcher of the Year competition has been accepting nominations since March.  They will continue to accept nominations until September, but why wait?  Nominate someone today who works hard in Clinical Research and deserves to be recognized.  There are separate categories of awards for CRAs, Study Coordinators, Project managers, and Clinical Study Teams.

I participated as a contestant the first year of the competition so I am now happy to promote and endorse the contest this year to all of you.  I made valuable networking connections, felt recognized by my peers, and had a lot of fun.  It was an absolute blast and I even took home a prize! I'm lucky to have great people in my network and each year I have recommended others. In fact, I've had at least one colleague at the competition every year!

Three Steps For Nominees to Complete

Once you nominate someone they receive an invitation to complete a questionnaire and confirm their interest in the competition.  The questionnaire is role-based and evaluates basic functional skills and knowledge of the regulations and guidance's related to their job.

The next stage of the competition is the "Clinical Competency Challenge: This requires candidates to respond in writing in no more than 1,000 words to three category specific competency questions and one further question, which explores the candidate’s reasons for entering the competition."

Finalists for this year's competition will be announced in October.

When I attended the finals, I was given a written challenge exercise where the topic was provided but I had to prepare a short presentation and Q&A session to a panel of judges; my presentation lasted about 20 minutes and I had less than an hour to prepare. All of the judges were pharmaceutical and CRO executives and they were attentive and supportive. I was asked interesting and thought-provoking follow-up questions and I had a lot of fun. Then, I had the rest of the day to meet my industry-peers, explore the area (it was in Philadelphia), and sweat it out in anticipation of the results.

The final phase of the competition and the much-anticipated award ceremony (black-tie/tuxedo) will be held 7 November 2013 at the Executive Briefing Center, SAS Campus, Cary, North Carolina (my hometown - they should invite me to be a judge!).

Nominate Someone Today

Go ahead and use this link to nominate that awesome Study Coordinator you loved working with, CRA rockstars (less than 4 years experience and Senior CRAs), and/or Project Managers.

Do you deserve to win?

Well, why don't you prove it by nominating yourself!  This competition is open to US residents only - good luck!

Related posts from The Lead CRA archives:

Monday, June 24, 2013

Are you at DIA? #DIA2013

This weekend, many clinical research folks headed to Boston for the 49th annual Drug Information Association conference.  Although I didn't make it this year, I'd love to hear from you if you attended; especially if you are a Clinical Research Associate.

Is the conference valuable for CRAs?  Would you like to share some highlights of your experience in a guest post or comment here at The Lead CRA blog?

This weekend I kicked off a new blog series at The Clinical Operations Toolkit blog called "The Buzz" and I listed the posters, sessions, and workshops that caught my interest.  If you do go to the conference and attended any of these, I'd love to hear your impressions and takeaways here or via email.

DIA 2013 - The sessions I regret missing: Part 1, Part 2

Have a fun week at DIA!

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

Thursday, June 20, 2013

The Lead CRA Interview with an Independent CRA

The Lead CRA asks: Annmarie, when you show up on site you always have your objectives planned out. What kind of prep work do you complete prior to visiting a clinical site for the first time?

Annmarie: I send a detailed confirmation letter indicating my goals and expectations. So that the site clearly comprehends what will be occur during the visit.  I also generate a site folder that is specific to the site.  Within this folder there is a section for site location/staff contact/lodging.  A section for Regulatory and Pharmacy along with an up to date copy of the Screen/Enrollment Log.  I also include a section for correspondence that I might want readily available and on hand.
Dress like a professional.  You are representing the company and you are a reflection of them...."a pet peeve of mine"!!!!

After the first visit is done, what kind of monitoring visit preparation is required for interim monitoring visits?

I prepare another detailed confirmation letter that clearly specifies the date* and time of arrival to the site and departure, objectives of the visit, and outstanding action items that need to be resolved prior to my departure.
*It is important to reserve enough days during the visit to accomplish all required and planned activities.  I typically confirm all my routine monitoring visit before departing the site at the conclusion of every visit.
 Now that I have met the staff in the previous visit. I put a lot of thought into my "communication techniques" that would work best with the personalities of the site staff in order to successfully accomplish my goals for the visit.
Be are part of a team (or an additional set of eyes) that only wants to ensure that the data is clean and that the subjects are safe. Presenting yourself in this manner will make the site staff want to work with you and for you.

You enjoy a lot of flexibility as an Independent and you make your own work schedule.  What is your favorite thing to do when you are not on the clock?

I love being a wife and mother of 4.  My kids range from 25 down to 13.  We are avid boaters and live on our boat all summer long. What I consider "my time" is yoga, running and when I take long walks with my 150lb Newfoundland dog named "Bella".  For whatever reason she really relaxes me after a long hard day.

Your business is all about referrals and personal connections, any networking advice?

Integrity is the key. Only recommend, work, or refer someone that you hold in high regard because Monitoring is a very small world. The people you affiliate with are a "reflection" of you.
Special thanks to June's first guest CRA blogger, Annmarie Schaden, RN, CCRA.  Annmarie is a talented Senior CRA independent consultant for hire residing in Michigan.  She is a brilliant monitor with special expertise in monitoring early phase, Phase I units, CNS, cardiovascular, HIV, infectious disease, and oncology trials.  Annmarie is a licensed nurse in Michigan with extensive experience in pulmonary/cardiac medical and surgical intensive care, the Emergency Room, and home health care for oncology and pediatrics.  She is a member of DIA, ACRP, and ANAC and she is recommended by The Lead CRA.

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Thursday, June 13, 2013

Risk Assessment in Monitoring

Clinical trial monitoring necessitates timely and accurate risk assessment. Risk assessment has become particularly relevant given that industry pioneers are increasingly and aggressively considering a risk-based monitoring paradigm. This paradigm is endorsed by consortiums like TransCelerate and supported by guidance issued from regulatory agencies such as FDA and EMA. So, how should a CRA assess risk accurately? What should be the balanced approach for site monitoring given that it is a cost intensive exercise with patient safety and quality being at the core of it?

Framing and classifying risk correctly

Acknowledgement of risk in the right context is important prior to its assessment.   Known or fixed risk factors at a program or protocol level should be considered first. At a program level, these risk factors could pertain to organizational dynamics, operational complexity (nature and extent of outsourcing), investigational product class, logistics and supply chain. Protocol level risk factors (such as TA, number of invasive procedures etc.) and site-specific risk factors (such as site experience, historical site performance etc.) should be accounted for, before developing the monitoring plan. Dynamic or unknown risk factors should be looked at using a relevant set of risk indicators to help evaluate the unknown risk elements during the progress of a study.

Using the correct risk indicators

It is important to identify risk indicators that serve as the right trigger to recalibrate monitoring activities. These indicators should be direct or surrogate pointers to   issues and risk that arise during the course of a study. A reasonable set of indicators for tracking site and study performance could be centered around quality, timeliness and efficiency. Timeliness of data entry, query resolution timelines, number of protocol deviations and adverse events; screen failure, early termination and site enrollment rates, are all good candidates for ‘signal detection’. Analytics-driven dashboards that provide trends and benchmarked assessment of these risk indicators for all sites in a study and that help identify outliers across the study performance spectrum are excellent tools to leverage for better risk assessment. Site performance across these indicators should ultimately convey a message that builds trust of regulatory agencies, in the quality of data being captured and reported during a clinical trial.

Leveraging technology to improve risk assessment

Successful adoption of technology, data integration from disparate sources and leveraging analytics optimally is critical for improving monitoring efficiency.  Cohesive technology-based monitoring solutions can assist greatly in early and ongoing risk assessment, by leveraging the real power of EDC systems to focus on critical processes and critical data. These targeted monitoring solutions should link protocol objectives to endpoints to ascertain risk and enable adjustment of monitoring activities in real-time. Leveraging technology-based solutions early on, through a quality by design-based approach during protocol and monitoring plan development, is ideal to mitigate risks at the later stages of a trial. Adoption of EDC systems supports remote and continuous transcriptional verification of clinical data; rather than as a retrospective exercise.  This keeps the quality and costs in control while keeping focus on aspects that “matter more”.

Verifying or reviewing the relevant information

The practice of doing 100% SDV is now being seriously questioned from a need and ROI perspective. Data analytics from the Medidata Clinical Cloud™ - based on thousands of clinical trials across the globe indicates that nearly 97% of clinical data entered for the first time is available for downstream use in its final form. Initiatives such as TransCelerate support that SDV has minimal effect on data quality – only 7.8% of total queries are SDV-generated and a smaller subset (2.4%) of queries are generated for critical data. Monitoring activities should cover both transcriptional verification (Source Document Verification or SDV) and SDR (Source Document Review), the later revolving around investigator involvement, protocol and guideline compliance. SDR is more important from a quality and regulatory approval perspective and therefore technology-enabled offerings which holistically address these aspects of the clinical development spectrum are likely to be more valuable to site monitors and CRAs.

Managing and mitigating Risk

Ongoing assessment of risk based on pre-defined risk indicators, critical processes and data should be the foundation of any monitoring plan. When needed, monitoring activities should be scaled up with the expectation of returning to the standard level in future. This return to baseline should occur post a root cause analysis of issues, thereby mitigating future risk. The approach of recalibrating verification and review activities should be closely aligned with the technological capabilities before the start of a study. It is important for monitors to reinforce expectations around data entry and query resolution timelines and ensure adherence to predefined SOPs and workflows stated in integrated risk management plans. This holistic approach involving data-driven process change and technological enablement, which starts early on with protocol design and site engagement will empower monitors better to perform their duties effectively.

Author information:

Associate Product Manager, Medidata 

Geeks Talk Clinical
Geeks Talk Clinical Medidata Blog

Special Thanks to today's guest contributor, Medidata.  Will you add to the conversation?  I invite you to author your own Lead CRA post. I'm accepting new guest contributors now, send me an email if interested.

Further reading at the ClinOps Toolkit blog:

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Tuesday, June 11, 2013

You are The Lead CRA: Five Years Later and a New Blog Format

Somehow I managed to completely miss my blog a long shot.  I've been the Lead CRA author for over five years and thanks to your collective 250,000+ visits the project has been a personal success and very rewarding.  In October of 2007 I started the blog as a place to catalog my adventures in a new regional CRA role and had a tremendous amount of fun shaping the Lead CRA into my personal brand.  I published once or twice a month, communicated with many of you via comments and email, mentored several new CRAs to help them kickstart their monitoring careers, began speaking at conferences, and made a lot of valuable professional connections.

Where Did the Time Go?

Along the journey I worked at a couple of excellent CROs and I am grateful for that experience and a series of important managers, mentors, and friends that have all helped shape my career.   However, I transitioned from Lead CRA into a Clinical Program Manager role a few years ago. I still interact with monitors and in-house CRAs as part of my role, but I am more rarely on-site where the clinical trials are being performed. When I do travel, I am not monitoring but rather overseeing the operations of many trials within the clinical program.  I have relationships with individuals at study sites but in many cases I actually delegate site relationship building and maintenance to the CRA Site Managers, most of whom I do not directly manage.  As a result of my evolving role in clinical trials management, I'm finding it more challenging to keep the content here current, relevant, and interesting to CRAs.  

What's Next for the Blog?

Actually, I'll be focusing my blogging efforts moving forward on a new project I started last month, the Clinical Operations Toolkit.  I invite you to follow along if you are interested in Clinical Trial Management.

I'll pop in from time to time to author a Lead CRA post here and there.  I'll still stand by for your emails, review and respond to comments, and we can stay connected on The Lead CRA Facebook page.

Do You Have Something to Say? How about writing the next blog post?

So, this was my blog for over five years, but now it is your blog; you are the Lead CRA.

My vision is for this project to evolve so that the bulk of the new content is generated by you and other CRA or industry experts.  You'll start seeing new authors here, beginning this week.

If you'd like to write a post for the Lead CRA blog please contact me via email.  I am available to suggest topics and I will help you as needed to write and edit the content.  Please join the conversation, you are now the Lead CRA.

Thanks again!

I'm looking forward to staying connected!  Thank you for your support, encouragement, and loyal readership over the years.


Wednesday, June 5, 2013

Monitoring Visit Follow-Up Letters

You’ll send a confirmation letter (or email if your SOPs allows it) prior to every monitoring visit, be it a pre-study qualification visit, a site initiation visit, routine monitoring visit, close-out visit, etc.  Then you’ll need to document your visit findings in a monitoring report.  Finally, you will send the principal investigator a follow-up letter summarizing the visit and discussing any critical findings or action items.

Create Your Monitoring Visit Follow-Up Letter

As a rule, I try to keep the follow-up letter to no more than two pages.  It is best practice to have the letter completed, reviewed, and sent within 7 days of the visit.  I write the letter to the Principal Investigator (PI) but Cc in the coordinator and trial TMF and/or the regulatory person, my Lead CRA or Project Manager, etc. as appropriate per my SOP.
your Lead CRA or the Sponsor may want
to approve the letter or provide a study-specific
template so check with your Lead before you send it
I dedicate the first sentence to listing the personnel who were present at the visit and thanking the study staff for their time and attention during the visit.  Be sure to include the dates of the visit as the letter will be filed in the Site Master File and the dates should match the Monitoring Visit sign-in log dates.  This is a good point to discuss any staff changes or recommended re-training.  Next I typically document the progress of study enrollment and then proceed to summarize the status of the Site Master File review, source data verification, and Case Report Form completion.

A Summary, Not a Novel

I break up the content where possible by using in-text tables or bulleted lists to note the following items as appropriate per the trial monitoring plan and SOP:

  • Informed Consent tracking details
  • Summary of patients/Case Report Forms reviewed
  • Site Master File or Source Documentation deficiencies/inconsistencies or Safety Findings
  • Protocol Deviations or Critical Findings (and appropriate recommended corrective actions as discussed with my regulatory contact, PM, or Lead CRA)
  • Supply Issues: lab kits, Investigational Medicinal Product, source documents, etc.
  • Action Items: resolved since last visit, new pending and wherever possible

No Surprises

My most important tip for follow-up letters is, “no surprises”.  During your time on-site you should be meeting with the PI and discussing the status and progress of the visit.  You should be summarizing your findings and discussing any issues so they can assist you to resolve everything while you are on-site.  If there are deviations or safety issues that need to be reported to the IRB, you can remind the Investigator of their responsibility to do so.  You can also provide re-training on the protocol or study procedures during your meeting on-site.
The Follow-Up letter should be
a recap of your discussion, not a news flash

In regards to action items, it is best practice to resolve everything before you leave the site to the extent possible.  I have extended monitoring visits to an additional day with approval from my Lead when there were items I would be able to complete with an extra half a day or so rather than leave pending.

If you are unable to meet with the PI during the visit, document this in your follow up letter and include a reminder that you are available by phone to speak with the PI.

Follow-Up Letter Template

I’m not planning to post a template.  Please don’t email me for a template as you can easily make your own using the guidance from this post that is study-specific for your trial’s needs.

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Sunday, May 19, 2013

Financial Disclosure Forms

In February the FDA issued industry guidance for the collection of financial disclosures.  I've summarized and called out a few of the sections I found most interesting.  There were certainly some items I hadn't thought about in a while so the refresher and clarifications were helpful and the appendix of Q&A was also useful.

Why are financial disclosure forms (FDF) collected?
The idea behind collecting financial disclosure information is to discover any potential bias on the part of investigators so the agency can consider this as part of the evaluation of the marketing application.  As sponsors, we try to avoid bias in trial design by using blinded randomization, placebo control, independent statisticians, specific evaluation methods, multiple study centers, etc. or other measures to minimize bias regardless of financial interest.

"Part 54 (21 CFR § 54.4(c).) does not categorically prohibit financial interests or arrangements, but it does require applicants to submit a list of clinical investigators who are full-time and part-time employees of the sponsor and to disclose or certify with respect to other investigators so that FDA can assess the possibility of bias."

Is this for every study?
Actually, the guidance covers in great detail the definition of covered clinical studies. Pretty much, all trials that support and NDA are considered covered but “This would, in general, not include phase 1 tolerance studies or pharmacokinetic studies, most clinical pharmacology studies (unless they are critical to an efficacy determination), large open safety  studies conducted at multiple sites, treatment protocols and parallel track protocols.”

What are the threshholds?
Payments for reimbursement of the conduct of the trial are not considered reportable, but grants, stock issuance, and other sorts of payments (i.e. consulting, honoraria) amounting to over $25K should be disclosed as well as any equity interest in the sponsor for up to a year after the trial exceeding $50K. 

So we’re not just talking about cash here.  The guidance spends a lot of time discussing “significant payments of other sorts (SPOOS)”, too.  This could be equipment or resources purchased for the investigator but NOT necessarily for use in the trial, entertainment costs, etc.  It could even apply to patents, proprietary interests, or future royalties (probably even more common in a device or diagnostics trial as opposed to a drug study).  For example, if you are validating a Quality of Life questionnaire or some other new assessment in your trial and a group of the investigators developed it, they might have a financial interest to disclose if they stand to make significant royalties within the year after the conclusion of the trial.

Remind the investigator to complete the form considering their financial interests and also the combined interests of their spouse and dependents - this statement is easy to overlook but can affect the dollar amount or arrangements requiring reporting.

“Materials [that are not considered SPOOS] could include the product under study as well as other products and/or equipment that are needed for the conduct of the study, such as ancillary medication and equipment used in testing required by the protocol.”

What if no Financial Disclosure was collected?
The agency requests that the “certification by the applicant that the applicant has acted with due diligence to obtain the information but was unable to do so stating a sufficient reason.”   We request an FDF prior to study initiation at an investigative site and then during monitoring we request updated financial disclosure forms if there is a status change.  At the conclusion of the trial we remind the investigator of their obligation to provide prompt updates in the year following the trial if their financial interest status changes.

What actions can the agency take?
“If FDA determines that the financial interests or arrangements of any clinical investigator raise a serious question about the integrity of the data, FDA will take any action it deems necessary to ensure the reliability of the data (21 CFR § 54.5(c)) including:
1. Initiating agency audits of the data derived from the clinical investigator in question;
2. Requesting that the applicant submit further analyses of data, e.g., to evaluate the effect of the clinical investigator's data on the overall study outcome;
3. Requesting that the applicant conduct additional independent studies to confirm the results of the questioned study; and
4. Refusing to treat the covered clinical study as providing data that can be the basis for an agency action.”

Do financial disclosure forms get submitted to the FDA?
Actually, no, the forms filed in the site master file are in the sponsor and site files but should be available for inspection upon request for up to 2 years following the approval of a new marketing application.  Also, it is entirely up to the sponsor on how to collect the financial disclosure statements as efficiently and completely as they would like.  The sponsor/applicant does provide a list of clinical investigators who do have financial interests on a Form FDA 3455 (Form FDA 2454 for investigators with no disclosable financial interest)but individual financial disclosure forms are not part of the submission and can even be maintained in an electronic certified copies rather than paper.

Can a sponsor submit the data if there was no FDF collected in every trial?
The short answer is yes, but the guideline covers in detail the obligation of an IND/IDE holder to demonstrate due diligence in having attempted to collect FDF from all applicable trials (see page 9 of the guidance, so much of the financial information is discoverable through filings of public companies and in financial records so the guidance suggests searching all available records to uncover financial interest that meets the reporting requirements).  The guidance discussed some legacy studies and other Phase I and earlier trials that don’t actually need FDF (although it is industry best practice to collect for these trials anyway).

Anything else I should know?
I found the sections on foreign studies, investigator –led/academic trials, multiple sponsors/change of sponsor, and waivers interesting and those are recommended further reading.

Thanks for following along on my summary of this new guidance.   These are non-binding recommendations so for your particular study, always consult with your legal and regulatory experts and I encourage you to read the regulations and guidance for yourself in order to apply them.  Remember that your companies working practices and SOPs will necessarily be more over-arching than the guidance and you should stick to those and discuss with your internal experts if there is any conflict. If you have additional thoughts or opinions on Financial Disclosures I would love for you to email me or leave a comment here or at The Lead CRA Facebook page.

Thursday, February 28, 2013

Monitoring Tools & Notes

As a regional monitor, I have primarily worked on studies with a conduct period of only a few months.  For these trials, I can typically monitor an entire subject’s source in just a couple of monitoring visits (IMVs).  However, I do use a few monitoring tools to keep me organized and assist with report completion.  I obtained most of these templates and advice from other talented CRAs I've been lucky enough to co-monitor with; special thanks to all my wonderful resources who have been open to sharing tips and tricks along the way.  For studies that last longer than a few months, these tools could be especially handy for resuming monitoring across multiple IMVs.    These are some of my standard and favorite monitor tools:

Generic Calculators & References
Never leave home without a date wheel!

Study Specific-Calculators & References
  • Visit Window Excel Calculator
  • Drug Compliance Excel Calculator (if you aren't an Excel guru then ask your Lead CRA or one of the Data Managers to help you out)
  • Pocket-Sized Protocol (If you have a PDF or word version of the protocol any copy shop can produce a little spiral bound or gum-bound booklet for you for around $30-$50....worth every penny and you can probably pass it through an expense report - check with your PM)
  • Study-specific CRF Completion Guidelines
  • Essential Document Tracker and TMF Submission Form
  • Recent Correspondence, Study Newsletters, etc. (nice to have printed on hand so if there is a gap in the Site Master File I can just I can just leave a copy behind at site)
  • Blank Study Forms 
  • Mocked-Up Study Forms (I have worked on several psychiatric studies that utilized SCID, MINI, or a similar scale/questionnaire to screen for exclusionary criteria.  Since the questionnaires can be so long and involved, having a properly (or prohibited) completed form to compare to the source can be a huge time saver and serve as a checklist. 
Monitoring Report Template and Follow-up letters & Action Item Logs
The most important thing you can bring to every visit is a blank copy of the monitoring report, in my opinion.  Your goal should be to complete as much of the monitoring report as possible while on-site.  If you take your monitoring notes in the report template, you have less paper to keep up with and this will really increase the quality of reports.  The longer you wait to write a report following the visit, the lower the quality -- document your findings while they are fresh.  A monitoring report template also serves as a great checklist to ensure that you don’t forget to do all the routine tasks (like sign the monitoring log, check the temperature records, etc.)

IMV Specific Monitoring Notes & Stickies
If you use a monitoring notes log,
consider producing the log on colored paper or NCR
so it is easier to keep track of in a pile of documents.
Post-it Notes stickies are great for flagging discrepancies and other items that need attention in source documents (blank fields, missing signatures, headers incomplete, etc.) but these can fall off or the coordinator may remove them once complete so that makes going back to verify they have been addressed difficult (I usually flag on the top and ask coordinators to move the sticky to the side to indicate it has been addressed rather than remove it).  I like to number my stickies and/or add little notes to them.  Then I can track the stickies in a subject-specific log like the example here.  

Some CROs and companies discourage the use of formal monitoring notes and stickies (as they can potentially lead to avoidable audit findings if left behind in a source binder) so do check with your Lead CRA to make sure using these types of tools is permitted.  

Don't write things down twice, try carbon paper!
I review my monitoring findings with the Study Coordinator or PI at multiple check-in points during the visit and sometimes they like to take monitoring note sheets with them back to their desk to work on the items while I am there.  If we aren’t able to resolve everything while I am on-site I photocopy the monitoring worksheet so I can write up the action items in my report and review that everything was addressed at my next visit. 

I have also made my monitoring notes on NCR carbon paper before and this has been extremely handy for me in order to leave a copy for the coordinator.  You can have your monitoring note worksheets pre-printed on carbon paper at any copy shop or you can buy the paper yourself to use in your own printer or to fill out by hand.  Also consider just bringing along a perforated carbon paper lab notebook or tablet if you anticipate leaving lots of to-do items behind.

Subject-Specific Monitoring Worksheet 
So again, my goal is always to write as few notes as possible while on-site.  I try to just document everything directly in the monitoring report template, follow-up letter template, and Clinical Trial Management System (CTMS).  That said, it can be useful to have some subject-specific notes when pouring over lots of medical records or extensive source documents.  Your subject-specific monitoring notes worksheet can also be a helpful reference at future visits or when completing authoring a report once you leave the site.  If you develop a little study-specific template, you can easily track out-of-range lab values across visits, ensure that all required protocol tests and procedures were completed, more easily fill out site payment or CTMS trackers, monitor consistently and more efficiently, etc.

Aim to only track things that wouldn't necessarily be recorded in the CRF or monitoring report but could potentially adversely impact subject safety or data integrity.  For example:
  •  If lab values are abnormal at a visit, how long do they take to return to normal? Are the AEs recorded properly?
  • If AEs are occurring, are new Concomitant Medications being added? Is the dosing of Investigational Product being adjusted?
  • Who is completing each assessment (same person each visit?)
  • Are all study drug kits being returned at every visit?
  • Are there out-of-window visits or other compliance issues?

Base your Excel template on the study Schedule of Assessments
I also try to limit myself to a single page of notes per subject, front and back permitted.  I typically take the notes in Excel so I can copy and paste them into my report but if you prefer to have a printed template, consider the colored paper trick and use something durable like cardstock so you don't inadvertently lose your treasured notes in a paper shuffle.

What's in Your Bag?
So what other tools and templates do you find useful when monitoring?  Leave me a comment here, send me an email, or share your monitoring tips on my Facebook page.  

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Thursday, January 31, 2013

3 Simple Ways to Improve the Approach

I was invited to speak on a panel this week at the Outsourcing in Clinical Trials West Coast conference.  This was my second year in attendance and the conference was an excellent investment of my time with lots of great networking and informative sessions.  The topic for my panel was “Examining mistakes some vendors make when approaching new clients to build and strengthen outsourcing partnerships”.

For the blog, I thought it would be a fun exercise to summarize a few key points brought forth by my fellow panel members.  However, I will flip it around by adding my comments on how each of the take-aways apply to our roles as monitors when establishing relationships with new clinical trial sites.  I’d also love to have your perspective so please email me at or leave a comment below.

I - Do Your Homework

You don't have to be a total stalker,
but a little internet research will help.
Our panel agreed that vendors can do a better job of learning about our company background, structure, and culture before they approach.  Most companies have a website and a lot of this information is listed there in a Mission Statement, Pipeline overview, Investor Reports, Press Releases, etc.  Anyone can google a company for news within the past 12 months and get a good idea of what the current challenges to the business are. You can also search by sponsor at to read a lot of details about past and current trials including who to contact, who the investigators are, and basics of the trial design. With this information in hand, vendors can tailor their approach to only offer the services and products that are most likely to be of interest rather than going through the whole dog and pony show.

So as monitors, here are some of my ideas on how you can you better prepare for a first site visit or any other in-person meeting with your site personnel for the first time.  It goes without saying that you should already know all the ins and outs of your protocol, be able to speak intelligently about the drug program, Investigator’s brochure, study tools, and the sponsor before you meet with any site personnel.  So let’s focus instead, on what you can now easily discover about the site.  Well, presumably you have the CV of the Principal Investigator and some of the key study staff.  Figure out when they graduated and where they completed their residency.  See where they grew up. Read through all their experience, have you worked on similar studies? Have you visited their home state? Do you have anything in common with their background that you could possibly use as an ice-breaker in the introduction?  If they are published, locate titles or abstracts so you know where their research interests are.  Consider bringing along a relevant recent journal publication or news article that you can pass along.  Google their office or research center to see if they have a website so you can learn more about their practice or recruitment strategies.  Are they on facebook, twitter, or other social media sites?  Many doctors have been reviewed by their patients on yelp; this can be enlightening.  Ask around with other regional CRAs you know who have worked in that therapeutic area if they are familiar with this site or any of the employees.  Maybe your company has an investigator database and you can glean some further insights there?  Go on and see what other studies they have done (you may need the location name of the site rather then the PI name to get any results or you can use the map). Now you can ask about their specific experience in other trials and head off any of those same challenges in yours.

By the way, you don’t have to tell them how much research you did or hint around too much (since you might seem like a stalker) but if you do this homework beforehand, you are going to be more prepared for the meeting and better able to find common ground and guide the conversation, trust me.  Since you now know so much about your site, you can easily tailor your communications to their trial experience level so you can be engaging and helpful rather than patronizing, overwhelming, or boring.  You’ll have more meaningful dialogue and can probably learn a lot from them when you ask them for more details about their past experiences.  Finally, if you put in this time and energy to kickstart a relationship then you obviously respect and admire other people that you work with; that will not go unnoticed downstream.

II - Avoid the Cold Call
The dreaded cold-call sales pitch.
On the panel, we all explained that we are busy and our time for vendor selection is limited.  We have a very basic expectation that business development people will be sensitive to our time.  Now don’t get me wrong, I love free lunch, sticky pads, clickable pens, squishy stress balls, and laser pointers, as much as the next guy, but my time is valuable and if I meet with each and every vendor that calls me out of the blue, my performance at work would suffer because I would run out of time to fulfill my basic job responsibilities.  The sad reality for new vendors is that we’re just more likely to work with vendors and people that we have known and worked with before.  When I get a cold call and they say “Is now a good time to chat?”  If I say “No” that is not an invitation to rattle off 10 bullet points quickly before I put down the receiver.  I would rather they say, “no problem, I’ll send a capabilities overview via email and hopefully we can schedule some time to chat after that”.  There was consensus on the panel that conferences like ASCO, therapeutic area programs, DIA, ACRP, outsourcing, etc. are a much better forum for getting to know one another rather than the telephone.  We also rely heavily on referrals from our colleagues in the industry so please spend less time on cold calls and more time networking for introductions from your satisfied clients for new business.  If on the off-chance a vendor catches me on a cold call and I have 10 minutes to chat, I will ask very specific questions about capabilities and metrics used to track performance in similar previous trials and ask particulars about their relationships with other clients.  If you call me, I expect that you already know about my business as I work for a publically traded company.  Again, they called me so they need to be prepared and have done their homework (see point 1 again).  I am not just sitting by my phone all day hoping some random vendor will call me and then ask me to explain what my company is working on; the information is out there.

So you are a CRA assigned to a new site and you were told by your lead to make a site contact within 10 business days.  OK, so if you just call out of the blue will the coordinator be pleased to hear from you?  Most likely, no.  My recommended approach is to send an email introduction first.
“Hi, my name is NadiaBoBadia.  I am a CRA based in San Francisco and I’ve been informed that we will be working together on the trial.  I am really looking forward to visiting your site next month.  I’d love to call and introduce myself to you this week.  I’ll try you this Thursday at 10am EST.  I also have availability after 2pm and would be happy to phone you at that time or another time if it is more convenient, just let me know.  I am hoping we can chat for 10-15 minutes regarding next steps for working on this trial together."  
See what I did there?  I am 100% planning to call them; they can expect it and prepare for the call.  I also provided an alternative time so they know I understand that they have other priorities in their schedule.  The way I phrased it, no response nets a call at 10am.  If I said, “Should I call at 10 or 2?” and they did not respond I would have been stuck with a cold call.  One other benefit of this approach method is that if they are the wrong contact person, they typically write back immediately and let you know right away, which saves a lot of time playing tag.

During your first phone call be sure to ask what method of contact works best.  I personally LOVE talking on the phone and I always follow-up with an email summarizing the conversation for a contact report.  However, I do understand that exclusively email or even texting is preferred by some coordinators and I accommodate them.

III - Determine the Decision Makers
Who has the power of the purse strings?
When CROs, EDC providers, recruitment vendors, lab and imaging vendors, or any other type of outsourcing partner approach a new client, they should determine as early as possible who the decision makers are so they are pitching to the right person; get those people in the room during demos and discussions.  On the panel, we all agreed that it is important to navigate the layers within an organization to figure out who signs the contract at the end of the day.  Are there folks that need to be won over in legal and contracts in addition to clinical?  Many organizations have preferred provider relationships and master service agreements, which represent a barrier for new vendors coming in.  Most sponsor companies will require a quality assurance visit or a business assessment before inking a contract with a new vendor.  If the vendor can ask the right questions early in the process, they should be able to define expectations around the proposal process in regards to how long it takes and who needs to bless vendor selection and contracts.

As site monitors, we can also benefit by figuring out who is running the show.  It should come as no surprise that at many sites, the decision of who gets recruited for your trial (or whether your data is entered into EDC in a timely fashion) is often times up to the coordinator.  It really depends on the therapeutic area and how niche the disease state is, but for many studies, it is the coordinator who digs through the patient database and approaches prospective patients with the informed consent.  The manner in which the coordinator presents the trial will impact how appealing the study is to a patient and their caregivers.  You should test this assumption and find out if the key to your enrollment may in fact lay with your coordinator.  Just ask what process they used in the last trial to identify potential subjects.  Try chocolate – it helps.  Make sure the coordinator is behind your study and likes working with you.  The next step is to figure out how to motivate the people whose efforts will contribute to the study goals and milestones.

It never hurts to show up with chocolate.
Moving Forward
OK, and this is a little bit off topic, but what about follow-up after the approach? Whether your first meeting was the start of a beautiful relationship and butterflies/rainbows/lilies rose up around you or whether they slammed the door in your face and you were standing in the cold, you will hopefully be working together and want to grow the relationship.  Consider sending a handwritten thank you card or small gift.  Email a link to an article that might interest them or share a case study or industry tool or website (The Lead CRA blog?) that you have found helpful in a past study.  Stay on their radar without being intrusive and your relationship will grow stronger.   I’m enthusiastic about working on clinical trials and I love building new relationships.  I hope you found some of these tips useful and you can improve your approach when meeting new colleagues in this industry.  Share your perspective with me at or please comment here on the blog.

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Tuesday, January 8, 2013

Striving for Improved Investigator and Site Relationships

Last year I was invited to present at a conference in San Francisco; it was a wonderful experience. Here are this year's conference details.

5th annual Outsourcing in Clinical Trials West Coast

I was just organizing some files on my computer and came across the slidedeck, "Striving for improved Investigator and site relationships to achieve higher commitment and optimal patient numbers" that I created for my topic in 2012.  Since I never got around to sharing it with you all last year (except for those of you that provided notes and edits - thanks again!!!), please enjoy and let me know if you have any comments or other feedback.  I'll post it in a few parts since it was a long thirty minute presentation.  Part I is below. Part II Part III


Intro: As a CRA and Clinical Program Manager I have obtained a mix of pharma & CRO experience. I have worked in all phases of clinical research, I-IV and I have additional experience in regional monitoring & in Clinical Data Management. I am the author of The Lead CRA blog.
In every study as sponsors, we need great relationships to meet our program goals.  It is critical to form an understanding of endpoints in order to obtain quality data.
I am also very interested in your views and would welcome your sharing some of your successes via email or the blog comments.

Investigators participate in clinical trials for a variety of reasons including scientific interest , professional credentialing, ļ¬nancial remuneration, and as a means to provide new therapeutic options in their clinical practice.
What else motivates investigators to work on trials?
the attributes of the study
the organization running the study
to increase patient base, recruit into their practice
opportunity to consult with experts

Determining the motivators for PI participation in your trial is essential to a good feasibility and site selection initiative. Sponsors must choose the right investigators and also understand how to motivate them.

Get commitment to the trial for better patient enrollment numbers.
Why do we want relationships with our sites?
incentivize them to prioritize our study
achieve timelines 
have quality data

Your priority must be to make the PI and study staff stakeholders.  Be strategic and focus on the future of your drug development program(s).  There is a huge incremental cost to recruit new investigators at each phase of development.  Work to attract and retain your investigators.  Even if they are one-time investigators, ultimately, they will be the people you will market to in the future to prescribe/buy/promote your drug products. Relationships matter.

Difficult conversations  are easier to have in the beginning of a study or mid-conduct rather than at the last visit before data lock, or when it is time to sign off on the casebook, or in the context of a sponsor or FDA audit.
Interact before the Investigator Meeting 
Get protocol input 
Avoid capturing the wrong information
Save $$$ by making tweaks before rollout
Are there other sites we should be approaching?
Can you help us develop recruitment and retention materials?
Ask site staff to review CRFs and CRF completion guidelines and edit checks 
Request that your Study Coordinators assist in developing global source documents. This will avoid duplicating information that is obtained in regular clinic chart and head off downstream frustration

Engage beyond the Investigator Meeting
Be present at industry & therapeutic area conferences
Perform ambassador work and actually visit sites
Host teleconferences – invite Study Coordinators to speak and share best practices
Bring Study Coordinators to a destination round-table
Have a face-to-face meeting or "Town Hall"
Institute brainstorming panels (operational feasibility, safety oversight, recruitment strategies)

The Difficult Conversations
When communicating with study site personnel do not allow gripe sessions.  Insist on solution-oriented discussion.  If they have criticisms then ask the question, "What can we do better?"  You should acknowledge that you heard the criticism.  To ensure understanding and alignment, you can re-state the problem or concern before addressing any objections.

Engage beyond the Investigator Meeting – this is face-to-face SC session done to boost enrollment mid-study; it was held in Vegas at the Four Seasons.
Whenever you interact with your investigators, make reputation management your primary agenda.
Who are we?
How are we to work with?
What do we stand for?

At the face-to-face session pictured above we learned a lot about this specific trial that was struggling to enroll.  After lots of discussion, it turned out most of the Screen Fails were because subjects were not interested in committing to the long/difficult protocol.  The Study Coordinators took turns role-playing with one-another to address participant objections and explain the purpose and objectives of the trial.  They also offered tips and suggestions that allowed our sponsor to create literature and recruitment tools.  The sponsor decided after the meeting to allow re-screening of Screen Failures and more than 10% of the original failures "not interested" were enrolled.  The exercise truly demonstrated that the study team has the greatest influence on a subject’s decision to participate.  This face-to-face meeting really provided a new kick-start to enrollment and brought us closer as a sponsor to the site personnel.

continued in... Part II Part III

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