Lead CRA Blog

The Lead CRA is Moving

2013-07-15T23:40:00.000-07:00

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.

Subscribe Now

http://clinopstoolkit.com/about/subscribe

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.

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

2013-06-25T17:41:00.001-07:00

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.

http://www.usclinicalresearcher.com/

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:

Today in History October 2011
What Makes a Good CTA? February 2011
Dealing with Poor Performance Feedback April 2010
Who's Running this Study? August 2009
Am I getting a Bad Reference From a Former Boss? September 2009
How I Got Here January 2009

Are you at DIA? #DIA2013

2013-06-24T14:12:00.003-07:00

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:

New Blog Format: Guest Contributors June 2012
Motivating Your Study Coordinators February 2011
Investigative Site Recruitment Plan Sep 2010
The LeadCRA Facebook Fan Page

The Lead CRA Interview with an Independent CRA

2013-06-20T14:22:00.000-07:00

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 nice...you 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.

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

New Blog Format: Guest Contributors June 2012
Tips for Better Monitoring Visits March 2012
CRA Work/Life Balance June 2009
Routine Monitoring Visits March 2008
Lead CRA Questions and Answers

Risk Assessment in Monitoring

2013-06-13T13:03:00.000-07:00

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:

Shantanu Ganguly, Ph.D.

Associate Product Manager, Medidata

sganguly@mdsol.com

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:

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

New Blog Format: Guest Contributors June 2012
Tips for Better Monitoring Visits March 2012
Sponsor Furnished Source April 2011
Routine Monitoring Visits March 2008

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

2013-06-11T12:38:00.000-07:00

Somehow I managed to completely miss my blog anniversary...by 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.

Monitoring Visit Follow-Up Letters

2013-06-05T11:29:00.002-07:00

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.

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

Financial Disclosure Forms

2013-05-19T21:07:00.002-07:00

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.

Monitoring Tools & Notes

2013-02-28T21:22:00.002-08:00

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!

Height/Weight/temperature conversion
A date wheel for calculating the # of days between visits (checking for out-of-window deviations)
Nurse’s Pocket Drug Guide book
Medical Dictionary
Websites: webmd.com or drugs.com

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.

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

Tips for Better Monitoring Visits March 2012
Sponsor Furnished Source Documents April 2011
What to Pack for a monitoring Visit August 2008
Routine Monitoring Visits March 2008

3 Simple Ways to Improve the Approach

2013-01-31T19:06:00.001-08:00

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 theleadcra@yahoo.com 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 clinicaltrials.gov 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 clinicaltrials.gov 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 theleadcra@yahoo.com or please comment here on the blog.

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

Improved Investigator and Site Relationships January 2013
Meeting with a PI August 2011
Motivating your Coordinators February 2011
Selecting Qualified Investigators April 2010

Related Content from The Clinical Operations Toolkit blog:

Striving for Improved Investigator and Site Relationships

2013-01-08T15:29:00.000-08:00

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, ﬁnancial 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

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

Selecting Qualified Investigators April 2010
Investigative Site Recruitment Plan Sep 2010
Sponsor Furnished Source Documents April 2011

Improved Investigator and Site Relationships - Part II

2013-01-08T15:24:00.001-08:00

This is a presentation I gave at the 4th annual Outsourcing in Clinical Trials conference in San Francisco in February of 2012. It has been posted in three parts:

Click here to go back and review Part I
Read Part II below
Part III - conclusion

_________________________________________________________________

Support the sites in order to maximize subject enrollment of THE RIGHT PATIENTS, quickly.

Consider having the study medical monitor or other scientific/medical officers from your company travel and outreach to sites. Identify conferences where many of your important sites are attending and send a representative to discuss and promote the study.

Educate the sites in the following areas:

How is the sponsor credentialed?

• What is our experience in this therapeutic area

• Who are our advisors (if well-known)

• What other sites are we working with

Present Evidence

• Demonstrated safety and efficacy

• Why are we doing this?

• Explain issues in the Investigator Brochure (explain for clinicians technically and for non-clinicians in lay terms)

Why should PI share the resources and risk?

• What problem solved?

• How is this superior than other available therapies?

• Focus on objectives and endpoints of the trial

Translate protocol decisions

• Explain reasoning behind inclusion and exclusion criteria

• Defend design

• Explain sample size

• Describe planned statistical analysis

• How does this trial fit in the overall drug development program

Communicate timelines

• Share enrollment numbers

• Notify in advance of planned scientific advisory board meetings

• Adequately notify data entry personnel of planned data cuts

• Are there planned interim posters and abstracts?

Remind study sites that even a study that fails to meet all endpoints is an important trial to your company. Making go-no-go decisions on NDA candidates early is fiscally important. The trial needs to be enrolled as soon as possible in order to finish as early as possible and permit analysis of the data.

_________________________________________________________________

Keep messaging

tight, brief, and organized. Avoid complexity

What am I saying or adding with this?

Before you put together a super verbose newsletter or another unnecessary blast fax, apply cuts and edits. Make sure that every message is useful and comprehensive; balance the need to include all of the necessary information so you won't have to clarify later and there won't be ambiguity.

Same message, different method

Consider targeted messaging, some sites need different types of support depending on their experience and performance.

_________________________________________________________________

Avoid “machine-gun” approach and make sure messaging is timely, appropriate, and not overwhelming.

Communicate with respect

Monitor to ensure that your interactions are not unwelcome. In an effort to "keep in touch" with your sites you must treat carefully as to not barrage them. Be wary of any investigative site that might have resent for your company's involvement. The study site personnel do tend to interact across sites and you must always keep your reputation squeaky clean. Also monitor for negative responses to avoid damage to the reputation you are working to build.

Avoid band-aid approach

Allow for different messaging methods for different sites and be willing to tailor messages.

Continue on to... Part III - conclusion

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

Tips for Better Monitoring Visits March 2012
Motivating Your Study Coordinators February 2011
Routine Monitoring Visits March 2008

Investigator and Site Relationships - Part III

2013-01-08T15:02:00.000-08:00

This is the third and final portion of a presentation I delivered at a conference in February 2012 entitled: "Striving for improved Investigator and site relationships to achieve higher commitment and optimal patient numbers"

Click here to go back and review Part I
Click here for a link back to Part II
Read Part III - conclusion below

_________________________________________________________________

Thank your investigative sites often and genuinely.

What are they doing right?

Great care and consideration went in to choosing these sites. Surely you can think of something they are doing well and praise them for it. It is very important to recognize effort and address issues in a timely fashion. If the site is inexperienced or very busy, they might benefit from a Study Coordinator buddy program. This engages the problem site but also recognizes the helper site as a "model" site; it is a benefit to both sites.

Give 'em Goodies

Some tools and forms of recognition are free or low-cost. Here are examples from other studies I have used.

MD to MD brochures
In-service slidedecks for training within their practice
CRF revision guides
Mini-protocols
Newsletters
pocket inc/exc cards
dose modification and calculation cards
Visit window calculators/wheels
Laminated diagrams and figures

Pay them on time

Like you, the study sites are running a business and they have monthly expenses to cover; don't delay to pay. By providing timely reimbursements you demonstrate respect, fulfill your contractual obligations, and increase the likelihood that sites will work harder for you in this study and the next when. When the sites achieve their goals you should pay them.

_________________________________________________________________

Doing small, minimally time-consuming tasks will have a site jump through hoops for you…

How can you help them reach their goals?

Think about all the administrative items that are involved in terms of recruitment, enrollment, data entry/query resolution, and monitoring completion. My team and I have come up with lots of little time-savers to help our sites along the way. Sometimes it is as simple as a pre-printed FedEx label, making some copies, or sending an empty 3-ring binder they can used to stay organized. If there are forms or documents that are routinely filled out by all sites, have the monitors assist or provide example completed forms as you know the forms well and will be more familiar.

I love telling the story of a site that my team was brought in to rescue. They were behind by 6 months in data entry because 10 surgical charts had not been obtained from the hospital. We paid for the copies and sent a courier to pick up those charts (pictured above). The Study Coordinator had just been putting it off since it was an unpleasant task. We brought in lunch several days, trained her on the EDC system, assisted in flagging adverse events, helped her organize her subject binders, and sat with her as she worked through the auto-queries. It was a long but productive week and she was so grateful and quick to resolve all queries from that point forward because we had helped her catch up.

_________________________________________________________________

Ensure monitors have a deep knowledge of the protocol and any amendments.

This slide could really be a presentation topic in itself, but you must ensure monitors have protocol fluency.

Make sure monitors know which deviations adversely affect endpoint and how to report and re-train staff. If a subject finishes the trial but is not evaluable, you have wasted a randomization slot, you might not be able to power your study, and you have needlessly paid for monitoring and conduct and learned very little about your drug product.

If you can incentivize your monitors to help study coordinator's during their visits and reduce administrative burden rather than nit-picking them, your sites will perform better. It is a monitors' responsibility to be a partner, not an adversary or a hall monitor. It is your responsibility to remind them on this charge. They are the face of your company in this trial and your reputation rests with them.

_________________________________________________________________

Be flexible to review and adjust messaging in your study.

The bottom line is that good relationships matter. Solid relationships are obtained through:

1) listening

2) supporting

3) Training

Yes, you are in a rush to finish your study but don't let the shortsightedness of the endpoints prevent you from creating a lasting relationship that will endure throughout the entire drug development program. Align the entire study team in this venture and obtain buy in from the top down so you can take the necessary time before, during, and after the study to reach out to investigative sites with the best support and recognition possible. Best wishes for deep relationships and quality data.

_________________________________________________________________

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

Vacation Photos

2012-12-16T00:09:00.001-08:00

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

2012-11-22T13:56:00.003-08:00

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

2012-04-16T10:00:00.000-07:00

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

2012-04-15T20:04:00.000-07:00

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 closin g 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

2012-04-09T22:19:00.009-07:00

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

2012-03-04T21:19:00.006-08:00

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?

2012-02-03T19:45:00.000-08:00

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

2012-02-02T21:50:00.000-08:00

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

2012-01-14T19:38:00.000-08:00

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

The Memo to File or Note to File (NTF) is Overused

2011-11-18T10:06:00.000-08:00

These memos are often sloppy, contradictory, confusing, or alarming (I once monitored at a site where the PI had written the following memo “Although employees and family members of Dr. XXXX and this facility were enrolled in the trial XXXX, they were in no way unduly influenced or coerced to participate.” Ummm, wow, this was part of the study record and you can’t retract it under any circumstances). Memos to File have to be reviewed and reconciled between the Site Master File and the TMF. Frankly, there are better ways to capture the information i.e. training logs, protocol deviation forms, monitoring reports, etc. so why do many monitors insist that the site generate a million NTF? I actually ask my coordinators to take it easy on the memos and to avoid writing them unless absolutely necessary or at least after serious consideration.

Some Memos to File are global correspondence from the sponsor or CRO and are necessary to address operational issue or questions (expanded specimen shipping instructions, imaging vendor holiday operation hours, clarification on processes, tracking, substitution of lab kits, etc.) these are beyond the scope of my discussion here.

A Note to File may be well-intended but can also provide an
interested party or inspector with a roadmap to a finding – yikes!

On-site, a series of NTFs all with the same date, in preparation for an inspection, or as a corrective action from an audit are a huge red-flag for me as a monitor. Just document along the way, during trial operations, and avoid lengthy notes to file. Personally, when I see file notes, I get a bit suspicious and inspired to dig deeper to make sure I am being given the whole story. I propose that many NTF raise additional concern rather than actually addressing deficiencies.

Don’t misunderstand, I would propose that a NTF can be a good tool to supplement the clinical conduct record but please try to minimize how often these are used and ensure that they are accurate and contemporaneous. For example, a NTF can be helpful when you are explaining gaps in documentation or inconsistencies, “B. Hill received rater training on 11-Jan-2011 but the certificate is unavailable, please refer to the training log. “ I would tend to use a Memo to discuss trial-related gaps rather than subject-related documentation issues. A simple post-dated progress note in the subject’s source can address any ICH/GCP concerns instead.

I’ve used Memos to File to organize Site Master File binders “The pharmacy temperature log for this study is located in Suite 1027 and updated twice daily. Please refer to the original logs.” and also in the sponsor level TMF to address gaps or clarify, “CRF approvals are filed in section 7.1.2.” “Translation certifications are filed at TMF level 3.6.”

A Memo to File can also be very helpful to reconstruct a record of conduct or to explain corrections that are made to documents that might raise questions. For example, if an Informed Consent Form had a mistake (the wrong date was written, a signature was not obtained, an incorrect version was used, etc) it may be helpful for the study staff to generate a NTF to explain when the error was realized and what corrective actions were taken to come back into compliance. If the subject forgot to date then the subject could be asked to date at the next visit and the SC could write a note explaining why a later date was used. The corrective action could be additional site training and a procedure to review the consent form by a second person at the time of consent; this revision to the procedure would be helpful to capture in a NTF.

I am assuming this will be a controversial topic because monitors tend to be very passionate about whether these notes are a hindrance or a help; please leave a comment with your thoughts. There is no regulatory requirement to produce Memos to File but I think in some cases sponsors and sites can benefit from them at times…they are, however, more powerful when used in moderation. Oh, and if you produce a NTF please sign and date it, accurately.

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

Site Master File: Correspondence March 2011
Routine Monitoring Visits March 2008
Close-Out Visits July 2008

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

2011-10-12T08:07:00.000-07:00

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!

ACRP The Monitor Magazine

2011-09-05T13:45:00.000-07:00

The Association of Clinical Research Professionals (ACRP) has a very active chapter in San Francisco, California. When I first moved to California and wanted to become a CRA, the local chapter assisted me with some helpful connections and networking opportunities. I learned about a clinical research certificate program through a local university, attended seminars on clinical research topics and issues, and enjoyed various relevant educational events.

I've lapsed on my membership, I have not pursued ACRP certification, and I've never attended global conference, but I'm still on the mailing list. ;) Today I was cleaning up emails from the past few weeks (sorry readers, I have been slammed at work and I am over a month behind on correspondence - yikes!) and I noticed that the September Issue of the ACRP professional publication, The Monitor is offered for free online.

The September Monitor magazine topic may be of interest to many of you: Careers in Clinical Research. It seems to be another terrific edition with a diverse group of authors and every article looks interesting. Here is a sampling of some of the most relevant articles you can read in this online edition:

I Want to Become a Clinical Research Associate . . .But How Do I Get My Foot in the Door? by Jill Matzat, RN, BSN, CCRA, CCRT

The Seven Key Traits of the Great CRO CRA by Brenda Reese, RN, CCRA, BSN

How Can Professional Development Advance My Clinical Research Career? (An Interview) by Esther Daemen, BSN, CPP, CPM, PG Cert Bus Admin (Open)

and more!

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

How to Break In To The Industry January 2009
5 Career Tips for a Young CRA July 2011