All content copyright, Creative Commons Attribution-Noncommercial-Share Alike 3.0
Unported, with the attribution: "The Lead CRA Blog", and a link to the post.

Friday, November 18, 2011

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

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:

Wednesday, October 12, 2011

Today in History (and blog traffic statistics)

On October 12th:

  • 1792 – the first celebration of Columbus Day commemorated the 300th anniversary of Columbus' landing in the Caribbean in 1492.
12-Oct-1999: A teacup yorkshire terrier
named George (the author's favorite artist
from the band The Beatles) is born.
  • 1850 – The 1st women's medical school, the Women's Medical College of Pennsylvania, opens.
  • 1928 – An iron lung respirator is used for the first time at Children's Hospital in Boston.
  • 1968 – The music single "Hey Jude" by The Beatles tops the charts.
  • 1976 – The People's Republic of China announces that Hua Guofeng is the successor to the late Mao Zedong as chairman of Communist Party of China.
  • 1997 – John Denver, American singer dies at the age of 52 in a private plane crash.
  • 1999 – Sir. George Basil, a teacup yorkshire terrier is the only survivor in a litter of five (and subsequently adopted by this blog's author).
  • 2010 – Returning via airplane to San Francisco with her boss after nine Site Initiation Visits in less than eight weeks, the blog author, NadiaBoBadia is offered (and accepts) a free upgrade to the First class cabin. Remarkably, NadiaBoBadia is still regularly teased by her co-workers for not agreeing to surrender the upgrade to her supervisor. 
12-Oct-2010: NadiaBoBadia enjoys a complimentary fruit and cheese plate,
watches some TV in her comfy First class seat, and sends a
free glass of wine back to her boss who has to ride in Coach

    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, 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 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 URL with other Clinical Research Professionals so that we can maintain and grow readership.

    Thank you once again for following along!

    Monday, September 5, 2011

    ACRP The Monitor Magazine

    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:
    and more!

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

    Thursday, August 11, 2011

    Lead CRA Q&A: Meeting with a Principal Investigator

    Anonymous commented in... "Routine Monitoring Visits":
    Could you please give advice about how to deal with the "difficult" Principal Investigator who doesn't want to meet you despite the numerous efforts to persuade him? Any recommendation would be very appreciated! -May 26, 2011 2:54 PM

    NadiaBoBadia responds...
    Thank you for a great question.  I've partially addressed it before in a post from the archives called "Who's Running this Study?"  Even though Principal Investigators (PI) have made a commitment to personally oversee the safety and conduct of the trial (In the US, see FAQ for FDA Form 1572) they often can't find time to actually meet with the monitors during our visits.  This happens quite often so I definitely want to address your question.  Remember, that there is no regulatory mandate that we talk to the PI but certainly it is a best practice.  However, I don't want to understate the importance of regularly briefing with the PI.  Remember from my post on Routine Monitoring Visits that the PI discussion is an opportunity to address important topics that affect conduct, can positively impact data reliability and validity, and ensure vigilance in reviewing ongoing subject safety.  If your trial is still recruiting, meeting with the PI can be instrumental in influencing study enrollment (related post).

    My interest when I am monitoring is to meet all of my objectives as efficiently as possible and leave the site as soon as I have met my goals.  Guess what though, doctors are busy.  In turn, I offer my PIs flexibility where I can.  I do not insist that they drop everything and meet with me each visit.  Generally, I have more success when I schedule an appointment time (say 15-30 minutes) in my confirmation letter and confirm it a few days before arriving.  If the PI truly can't meet though, a telephone contact within 10 days of the visit will be an effective alternative for communicating important findings during the visit, pending items for resolution, or general study updates or training.  I document the call in my report, in a separate telephone contact report for the TMF, and/or an email recap.

    Trick your PI into a meeting! Tell the
    doctor there is a party they must attend and then tackle
    them with your visit findings - just kidding!

    Part of our goals as monitors are to prepare PIs for audits and also to influence operations of a trial.  We help bring corrective action for any missed procedures and help them document anything that may need to support the record of conduct down the road.  We help them defend their data and demonstrate that patient safety is protected.  The PI meeting furthers these goals so it is important to budget time for it.  Don't use the meeting just to criticize the "difficult" PI and the study site staff.  Give them kudos and tell them what is going well and also where improvements may be needed.

    If you pitch the PI meeting like this, act accordingly, and are respectful of the PI's time then the meetings are more productive and more likely to occur.  As you build a relationship with your PIs, they will see that you are committed to helping them conduct the trial properly.  As your PIs grow to trust you as a partner to their site, they are more likely to make time to meet with you.

    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:

    Monday, July 18, 2011

    5 Career Tips for a Young CRA

    I came across a fun little article on biospace that offers career advice: 5 ways to be a rockstar at work (via Biospace).  

    This post echoes the format of that article and I hope you will find it interesting and leave me a comment or email some feedback. 

    Although I have transitioned to in-house, the bulk of my experience as a CRA is in Regional Monitoring.  Reflecting back on the career tenants I stand by, I am sharing today my 5 best career tips for a new travelling monitor.

    1. Be a Partner
    • An auditing approach to monitoring will strain your relationship with the site staff.  You know the regulations that govern our work and you understand the study that you are monitoring including all the expected procedures, assessment windows, and special instructions provided in newsletters and in other study correspondence.  Your attitude can be to train the study site personnel and share with them this information to help them protect subject safety and data integrity, or you can go in and point out everything they’ve done wrong and focus only on the poor performance.  You can write a damaging monitoring report, cover yourself, and simultaneously ostracize the site but you will not have partnered with the site or introduced extra quality; you may be perceived as a bully or hall-monitor.
    • Don't "police" your sites too strictly.
      This approach is detrimental to
      quality relationship building.
      Remember that coordinators and Investigators have responsibilities beyond your specific trial.  I have addressed this in other posts such as 'Motivating Your Study Coordinators'.  If you can’t put yourself in someone else’s shoes you won’t be able to influence them to help you with your goals during the visit or in future visits.
    • At crunch time you will cultivate the relationships you have built. Need access to the site at a greater frequency or increased duration?  Need your coordinator to stay late and do some extra data entry or query resolution?  If you have been friendly and respectful to date, you improve your chances of getting what you need out of your sites – even at short notice. 
    2. Know your Metrics / Deliver Quality Results
    What is expected of you? How do you
    rank in performance compared to your
    peers?  Are you accountable at work?
    • You are being measured against your peers.  Approach your work in a task-oriented manner and ensure that you know which deliverables are due, when, and in what manner.  Deliver early and track your contributions. 
    • Be current on all training and don’t expect a prize for meeting this basic job responsibility.  Even if “nobody else is getting their SOPs done”, stay current on yours and don’t link your performance (or failure to perform) to others.
    • You’ll come to find that cultivating quality relationships and trust with your sites will go hand-in-hand with producing excellent metrics.  Focus on quality first and the metrics will follow. 
    3. Raise your Flag / Get Noticed
    Me me me.  Don't forget to highlight the successes
     of your supervisor and the collective team.
    Contributing to other people’s happiness
     and “ team buzz” will return to you in dividends. 
    • Pause and reflect as needed to appreciate your body of work.  I keep a “praise” folder in my email to store thank you notes and stories of major deliverables I have met or produced.  I reference the “praise” folder as a pick-me-up when I am feeling overwhelmed and challenged.
    • Since you are always identifying your deliverables and finishing everything ahead of the deadline and tracking your contributions as I have suggested, you can provide this information to your immediate supervisor at 1:1s, in performance reviews, or in status report emails. 
    • Don’t overreach.  If you are promoting yourself to your bosses boss, you may be overstepping and actually undermining your current boss or creating animosity among your peers.  Tread carefully here.  Be humble and use good judgment.  
    4. Don’t Commiserate / Nobody likes a Debbie Downer
    Moaning about what isn't working is easier
     than focusing on what is going well or
    coming up with solutions to improve
     situations that are not ideal.
    Resist the temptation to commiserate
    • Your peer CRAs may live and work in cities far away.  They will have different financial circumstances, family backgrounds, tastes and preferences, and values.  Typically the easiest common ground when forging a relationship with your peers is to talk about work and the projects at hand.  Inevitably, this will lead to grumbling or complaining about the demands on your time, or a boss who just doesn't get it, or a lead who seems checked out, or a site that is difficult to work with.   You may feel you are “just venting”, but negativity is toxic, counter-productive, and a bad attitude will adversely affect your future career prospects.
    • If you have nothing nice to say, don’t say anything at all.  In every job you have to evaluate the gap between what you want from your ideal position and what you have in your current position.  It is your charge to reconcile that gap by identifying concrete and measurable outcomes that leave you satisfied.  If you simply cannot overcome the gap because of a corporate culture mis-match, timing, resourcing restraints, etc. you have to decide 1) Am I going to acclimate and deal? or 2) Am I going to bolt?  You should only be asking those two questions once you have exhausted every avenue to change your position into what you want.  These are the only two choices.  If you take things to their natural conclusion, you can stop being petulant and accept your circumstances or you can have the maturity to leave your position; either option is ultimately in the best interest of yourself, your boss, the organization, the sites, and the study patients that we are ultimately responsible to.  The scenario where you stay begrudgingly, and half-perform will likely eventually result in your termination. Your metrics will suffer, your relationships outside the office will be impacted, and you will be unfulfilled and miserable at work. 
    5. Be Patient  / Exercise Humility
    The best managers teach you that
    you can validate yourself and
    recognize your own accomplishments.
    • Your Lead CRA isn’t approving your trip request within two hours of submission? Give it at least a day and recognize that you are one of a team of many CRAs that your lead manages.  This, while your lead simultaneously juggles all of the other CRA Lead and ad hoc responsibilities.  Trust that your request is in the queue and chill out. 
    • Not getting the promotion you are ready for or the recognition you want after over-delivering on an important study milestone?  Keep reminding your supervisors of your contributions through status reports, performance evaluations, in 1:1s, or in a team setting. 
    • Great managers always have a pulse on your contributions.  Better managers always give you credit for a job well done.  The best managers provide acknowledgement strategically; they make you wait for it to teach you humility, maturity, tact, and solidify your role in the organization.  The quality expectations are very high with the best managers and therefore they reserve praise for only truly exceptional performance.  Feedback that you have to be patient for will prove to be your most valued feedback at work.
    You may also like...from The Lead CRA archives:

    Thursday, June 23, 2011

    Summer Vacation

    I hope everyone has exciting plans for the summer or at least a plan to beat the heat.  Temperatures in San Francisco were almost 75 degrees Fahrenheit this week.  I don't have air conditioning and my home is in the upper level of a beautiful Edwardian the top of four flights of stairs, this has been a scorcher by SF standards.  ;)

    I've planned a lot of exciting content for the blog in the coming months so I hope you will continue to follow along.  I've invited several guest contributors to help generate topics and content; I really can't wait to share some of the series' we have come up with so please stay tuned.

    I will visit Guangzhou, Dali, and Lijiang this summer.
    I had to get a new passport and visa because I ran
    out of space in my old one - can't wait!
    I am planning a vacation to Hong Kong and Yunnan province in July but I'll queue up some posts and address your comments and questions as I find time.  I've been corresponding with many of you via email but I have been on a bit of a hiatus from the official Lead CRA blog due to a lot of competing priorities at home and work; I'll include some of the topics of broader interest here for your perusal very soon.

    Thanks again for your loyal readership.  You can always reach out to me in the comments section of any post or email me at if there are items you would like featured or if you have any monitoring questions.  Here's to a wonderful summer for all you hardworking clinical research professionals!

    Wednesday, April 20, 2011

    Beauty Break

    More CRA related posts soon but today I am off-topic and burning through some birthday giftcards and shopping online.  I am going to share some of my favorite beauty buys with you loyal readers, hope this will be of interest.

    Can You Get Hooked on Lip Balm?: This book just arrived in the mail for me today and I can't wait to read it!  It is from one of my favorite blogs The Beauty Brains.  The blog is dedicated to explaining the science and debunking the myths about beauty products and makeup.  It has helped me save a lot of money by avoiding loads of beauty gimmicks.  The blog has also taught me to think more critically about the products and chemicals I use on my face, hair, and that I choose to put on my largest organ, my skin.

    Can You Get Hooked on Lip Balm?: Top Cosmetic Scientists Answer Your Questions about the Lotions, Potions and Other Beauty Products You Use Every Day

    Philosophy Microdelivery Purifying Peel: This is my once a week, brighten my skin, go-to face mask.  It combines Vitamin C and salicylic acid to promote cell turnover and leaves my skin ski-slope smooth and soft.  I have recommended this to all my friends and relatives.  Go to Sephora or Nordstrom for a sample.  I think you will return to purchase.
    Philosophy Microdelivery Purifying Peel

    Bare Escentuals Makeup:I think mineral makeup is a brilliant choice for travelers.  Also it is fun to apply and provides great coverage.  
    Bare Escentuals Sephora Exclusive Get Started Kit ($174 Value) Light

    Seanik Solid Shampoo by LUSH: My color-treated hair is super fine and I sport a travel-smart bob cut but it has been dry and tired so I just switched to a new shampoo.  I realize I am a little late to the bandwagon but about three weeks ago I discovered solid shampoos.  The lather is out of this world, conditioner is optional, and it leaves my hair squeaky clean with great shine and touchable softness.  The sea salt helps with lift and the seaweed helps prevent dryness.  Buy two and you get a free tin.  I also like Karma Komba but it strips my hair too much for everyday use.  You can overuse this product so just wet it, two to three quick strokes across the scalp and then massage in.  Applying too much will make the hair gunky and leave it weighty with product.
    Seanik Solid Shampoo by LUSHKarma Komba Solid Shampoo by LUSH

    Aveda Pure Abundance Hair Potion: I probably love this the most because of the novel application; it is just so fun to use.  You hold it at seven o clock, 4 inches form you head, and just apply a poof to the roots.  A powder mist of acacia gum turns into a creamy lotion that coats and separates the follicle to create tremendous lift. Imagine hair that has just had a day at the beach and great volume.

    Cricket Professional Friction Free 1.5" Brush: I love this round brush with the ergonomic handle and tourmaline barrel.  I can blow dry my hair and set with prevision and ease.  It does not snag or rip my hair and it is less than twelve bucks. 
    Cricket Professional Friction Free 1.5" Brush
    Remington H-1015 Ceramic Compact, Large and Medium Roller
    For more bounce these little travel hot rollers are great.
    They heat up in just a few minutes and tuck easily into your suitcase.

    CeraVe Moisturizing Cream: This pot of lotion creates a moisture barrier and has hylauronic acid which is important for cell turnover.  It has no artificial color and no fragrance.  It is perfect for sensitive or dry skin for daily use.  After application it isn't tacky or greasy.  
    CeraVe Moisturizing Cream 16 oz (453 g)

    Sonicare toothbrush: I had a coupon to pick this up at Costco and I love it.  The timer keeps me honest so I don't cut any corners in my brushing and that keeps my dentist happy.  This model has a special whitening mode, a travel case, a travel charger, and a UV cleaning system to sanitize the bristles.  The toothbrush stays charged for over a week. I'm a very satisfied customer and recommend this product often to my friends.
    Philips Sonicare HX6733/70 HealthyWhite 3 Mode Premium Edition Rechargeable T

    So, I am currently looking for an under-eye moisturizer and a makeup remover. I'm also open to other great product suggestions so feel free to comment or email me your faves. I'll return to CRA topics next post. Please forgive my vanity excursion. ;)

    Wednesday, April 13, 2011

    Efficiency Tips: Keep the Inbox and Sent Box Empty....and Archive Emails Weekly

    This is my Outlook folder list. I try to 
    keep the inbox at less than 20 items at 
    all times.
    Today is Wednesday. I have received/sent and processed over 300 emails. Other Clinical Operations people in my immediate working group see even more traffic in their inbox but I can conservatively say that around 120 emails per day is my typical average. A few folks in my department file nothing and just rely on the blackberry and Outlook search functions to run their email empire. However, I feel pretty panicky if my inbox goes over about 20 messages or so. I use my inbox as my tasklist and I rely on folders and flags to keep everything organized. I've developed a system over the years to keep my inbox slim and zen-like and today I'm going to describe it to you. I also try to review and file items in my Sent box at the conclusion of every day because I prefer to file email responses with the original thread and keep my Sent box empty (Outlook can do this automatically for any message sent from any folder rather than the inbox.  In Tools->Options->Advanced Email Options-> you can select "Save replies with original message").

    The batch process approach to filing TMF correspondence
    Most site managers I know wait until they are preparing to close out an investigative study site then they go back and read several years worth of emails, print out the ones they think should be filed (2 copies, one for the TMF and one for the site), carry the big bound stack with them to the site, and slip it in to complete the correspondence file. An issue with this approach is that it wastes a ton of time and paper plus you are almost assured to introduce duplicates since the coordinator has likely done something similar. Finally, you are assuming that A) you have time for this exercise at the end of the trial and B) that you will still be around/employed to execute this action. Sorry to be such a realist, but both A and B are not exactly solid suppositions. My approach is to file my emails weekly in the eTMF.  As a result, at the end of every week, I am confident that 90% of my TMF correspondence is filed. I am never more than two weeks behind.

    Keeping the inbox empty (or nearly empty...)
    I strive to process every email within an hour of receipt. When something hits my inbox I 1) delete it 2) respond to it quickly (and delete it or archive it) or 3) file it. Deleting an email straight away will save you time from re-reading it again; dump it! If the email doesn’t require action from me and I am not waiting on a response, I can just file that email or delete it. I have a folder for my manager/HR/corporate stuff and travel. I have a folder called Praise where I keep thank you notes and email records of major deliverables or accomplishments (this is useful at review time or when I need a pick me up after a defeating day/week). I have a folder for each study I work on. I have a folder for all sites in a study. I have a few folders to keep vendor communications. I have a folder called #Pending (the pound makes it sort to the top of my folder list) for anything with action indicated from me and that takes more than 2-3 minutes to address. I have a folder called #Waiting for things other people are tasked with but that I want to track or follow-up on. I have a folder called #File for items that may be candidates for the TMF correspondence section (no, I don’t file every email in the TMF).

    You actually have to Process #Pending #Waiting #File & Sent
    I deal with everything in #Pending (at least the items flagged Overdue, Today, and Tomorrow) in the mornings when I arrive at work and in the afternoon when I am wrapping up for the day.
    I use flags (Today, Tomorrow, This Week, Next Week) and group by flag to keep #Pending manageable.
    At the end of every day (or when I have a few minutes during the day) I go to my Sent folder and I group by conversation trail or category, delete most of the thread, and move the final message to #Pending, #Waiting, #File or one of my folders. Archived in a folder = no action indicated; never to be referenced again except possibly in a future search.

    I go through #Waiting at least once a week. When something in #Waiting is addressed by an incoming email message I delete the item from #Waiting or archive it in a folder.

    I process #File on Fridays or anytime the folder shows that it contains more than 50 items. I group it by category or stack it by subject line or conversation. I delete everything leading up to the final thread. I typically have about 15-20 actual emails to file each week and I copy those to our TMF. I can just drag and drop from Outlook into our Clinical Trial Management System.

    Outlook Features Help Me Stay Organized
    I use Outlook quick steps and rules to quickly file things and/or label/categorize (if an email goes to a certain person or has a certain site name referenced in the subject then it gets a label/category automagically for that site). I use Categorize extensively (newsletter, meeting minutes, issue, login credentials, one for every PI name, specific vendor, TMF, reference, reference doc, expense report, personal). I also use search folders, too (mail received this week, mail received this month, with attachments, logins, newsletter ideas, reference, reference docs, amendment items, mail to/from specific people).

    Correspondence Reconciled. Easy.
    Now that you are so organized, you can actually use correspondence to prepare for your visits and write your monitoring reports. A few days before every visit, I go to the Clinical Trial Management System eTMF, select all the correspondence since my previous monitoring visit and print it to one big PDF. I open that document when I am at the site and thumb through the correspondence that has been filed by the coordinator since my last visit (the coordinator always files new stuff in front of a colored piece of paper). If the coordinator has already filed the item I delete the page from my PDF. When I am all done I email the PDF to the coordinator (remember, the only pages left are the ones the coordinator did not have filed) and ask them to print it and we file it before I leave the site.

    I know this all sounds really intense but the system works for me and I have inspired several colleagues to adopt the system (at least in part). Try a #Pending #Waiting of #File folder. You might find that you have a useable and less intimidating inbox moving forward. Be warned however, the whole system falls apart though if you aren’t disciplined about reviewing your new #Pending #Waiting #File and Sent boxes at regular intervals. Please share any email efficiency tips or tricks that you find helpful.

    Tuesday, April 12, 2011

    Lead CRA Q&A: Sponsor Furnished Source Documents

    Anonymous commented in... "Perfect Clinical Trial Source Documents":
    Hi, some sponsors don't allow investigators to use source data worksheets/templates arguing that source data should not contain instructions nor any other items (logo, etc.) which would not usually appear on a patient medical file.  Is there any legislation which confirms this audit finding? -April 7, 2011 3:18 AM 

    NadiaBoBadia responds...

    Every required piece of
    data isn't already
    in the medical file?
    It would be great if the medical file captured everything we needed for every trial.  However, the reality is that sometimes source documents are required to capture supplemental information or observations that are above and beyond what would customarily be collected in the course of standard of care medical practice. For example, a patient Quality of Life survey, dosing and administration information, or PK lab draws.

    Honestly the hesitation to provide source docs with logos might be more of an intellectual property thing rather than a regulatory thing. I know when I worked at CROs we were very careful not to include sponsor branding or logos on the outside of binders or in papers that were in view. We opted instead to reference by study nickname or protocol number. When I monitor, if I see source documents for another sponsor (maybe a competitor) I can discover confidential information and learn about another drug development program; that is extremely proprietary. Many public and private companies have to defend their product rights in patent legislation so it is important to eliminate logos and branding just to protect property rights.

    Let's assume however, that these confidentiality concerns are not the reason sponsors don't allow source docs to have instructions, other items, or logos. I have worked for many sponsors that are careful to limit instructions given outside of the protocol to sites. That actually includes CRF completion guidelines, worksheets, and source documents. As sponsors, we have an obligation to produce a protocol that is clear and has scientific merit while protecting subject rights and safety. Some other reponsibiltiies include choosing qualified investigators, providing adequate monitoring, etc. but the regulations in no way require us to provide source documents. This is a gray area and some sponsors feel strongly that they should avoid actions not explicitily delegated as a sponsor responsibility because that introduces risk. Some sponsors do not want to provide source documents at all, let alone source documents with their logos and emblems dotted throughout.

    Allow me clarify with an example. If I generate source documents with blanks provided for all of the assessments required at a study visit but I leave one off (or worse, I include extra assessments) then that is in a way instructing the site personnel to deviate from the approved protocol. This is a huge no no because any changes to the protocol should be handled in an approved protocol amendment that is reviewed by an independent IRB. In operations, we face these issues all the time where we want to give sites instructions or clarifications that are outside of the protocol. If the instructions affect patient safety or the integrity of the trial we should always amend the protocol.

    So to recap, I'm not aware of any regulations that prohibit sponsors from providing source templates or even including their logos on source documents.  I am aware that some sponsors prefer not to provide source documents or to have their logos on the source for either confidentiality reasons or risk-mitigation reasons. To clarify further, sometimes we provide source documents because we are capturing something for a trial that would not otherwise be captured in the regular medical file. Hopefully that addresses your question. Otherwise, to further research the topic, I can refer you to ICH GCP E6 sections 1.51 and 1.52. Although "source documents" are not explicitly discussed in the regulations, FDA's CFR 312.62(b) you can read more in the relevant section "case histories".

    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:

    Saturday, April 2, 2011

    On the Road Again

    Remarkably, I've only taken three work trips so far this year.  Luckily, I have been doing transcons so my mileage balances and quest for elite status aren't suffering too terribly (12 segments and 17,000 qualifying miles in 2011).  That said, I haven't had a lot of travel stuff to report lately but here is a summary of this week's travel highlights.

    Read a Great Book...maybe not suggested in-flight reading
    I've read all of Atul Gawande's books and generally I enjoy reading non-fiction, memoirs, or other books/essays that can be digested in snippets since I don't get a lot of focused un-interrupted reading time.  His latest book (that I am finally getting around to reading), "The Checklist Manifesto" was no exception and I was easily able to tear through it on the flight from SFO->IAD (San Francisco to Washington Dulles).  A lot of the book tells stories of avoidable aviation disasters and the response to those issues in flight so be advised that maybe it is a little too chilling to read while actually on an airplane.  I thought it was really well-developed, interesting, and it still has me thinking about how I can apply some of the concepts to my daily work.

    I am not a surgeon or a pilot so my work isn't exactly life or death and I really do have time to ponder through problems and work out the right solutions.  However, just because I have that luxury of taking my time, should I really waste the time when I could free myself up for other more interesting assignments or simply produce more?  I just want to get things done. Right. The first time.  So using a checklist isn't about writing down a procedure from nuts to bolts.  It is about identifying what the critical or gating points are of any process and making sure those are done correctly and in the right sequence so that downstream errors are avoided.

    Some of the common problem areas we experience in clinical operations are sites that are not recruiting enough subjects, delays in study timelines or deliverables, and failure to communicate critical study information in a timely fashion.  I'm still thinking of others.  I really liked this book and I do recommend it.  I hope to develop a related blog series at some point after I have let the concepts percolate a little longer.

    TSA Full-Body Massage
    It may surprise many of you that I have all but avoided the new backscatter scanners since they were implemented last year.  I've just been careful about choosing the right security line, booking the right airlines, and avoiding the wrong airports.  Also, I've been lucky.  However, yesterday in Ft. Lauderdale, Florida I had my first opt-out.  The agent motioned me to the machine and I said, "No, thank you."  She explained that she would perform a secondary screening and asked me to go sit in a chair in a glass box off to the side of security.

    I opt-out because these machines have not been independently tested for safety and only my husband gets to see me naked.
    Did I mention my flight was boarding in 10 minutes?  Luckily I could see the gate from security and I knew I had an upgraded boarding pass waiting for me so I wasn't too worried.  Another TSA agent gathered all my belongings and followed me to the glass box.  He placed my items in bins outside the box and motioned for me to keep them in my line of sight.

    The female agent came over and explained the pat-down procedure.  She told me what areas of my body she would touch and when she would use the back of her hands.  She then asked if I would like a private room but I declined and allowed the security theater to continue.  I confirmed that she was using clean gloves.  She reached inside my collar, inside my waist line, and touched all of my private areas (I was wearing thin/slim black pants with no pockets -- mental note, do not wear skirts to the airport). The whole thing took about three minutes,was generally uncomfortable, and I didn't even get a kiss.   It was handled very professionally but I hope to dodge it in the future.  Thank goodness for the upgrade to first; I really wanted a free cocktail and a bath in Purell sanitizer after the TSA rub-down.

    Southwest Emergency Landing
    At least I wasn't flying Southwest.  Over 300 flights are cancelled today and they have grounded part of their fleet to review the integrity of almost 80 aircraft following a "mechanical failure" where the skin of an airplane ruptured following ascent over Phoenix and caused a hole in the fusealage, rapid de-pressurization, release of oxygen masks, and an emergency landing.

    Here's to hoping that I will be booking more work trips soon on my carrier of choice, avoiding the TSA circus-act, and that none of my future travel will be on Southwest.

    Thursday, March 24, 2011

    Efficiency Tips: Tackle the Correspondence Tab

    Group and Organize the Paper Monster
    That behemoth regulatory binder binder could definitely be less daunting. Section it out logically by slipping a colored piece of paper or a tab in to demarcate each quarter.

    Replace the binder
    A new binder is less than $5. If the rings are damaged and every time you flip a page entire chunks fall out or the holes get torn, stop fighting it and replace it.  Many of my sites have switched to a plastic bin system and use a hanging folder for each traditional tab. Finally, I can leave my three hole punch at home and making copies for the TMF is now a breeze. Sometimes I just put little colored stickies on the pages I want and I ask the coordinator to fax or scan them to me. When I get back to my office they are waiting in my mailbox and I just ferry them right over to the TMF room.
    Hanging file folders during conduct are a brilliant way to organize the SMF.
    Don't Put it Off Until the "Next Visit"
    Review the correspondence tab at every visit but don't reconcile the old stuff again until the end of the trial at close-out. How do you do this? Just bring a colored piece of paper with you to the site and write “Everything behind this {color} paper was reconciled against the TMF during the monitoring visit on {date}. Attn: Study Coordinator, please file any new correspondence in front of this paper and I will review and file at the next monitoring visit. Thanks! {your name}”. File it at the top of the correspondence pile so the coordinator sees it when they open the binder.  Simple, elegant, and it works. Try it!

    Other tips?

    Every Email is an Essential Document...or perhaps not

    Wait, you said I shouldn't file every email?
    Please, no, for the love of all that is Holy, don't file every email. I currently manage 15 sites and as a general rule, only about 1 in 10 emails I generate end up in the correspondence tab. This is because I do a lot of back-and-forth emailing with my sites. I never file the first email, just the final thread with the conversation trail included, assuming it is worth filing.
    Image courtesy of rmgimages.
    Items that are worth filing reference clarifications, demonstrate training and oversight, address GCP issues, discuss protocol deviations, and document conversations involving the Medical Monitor. I have trained all my coordinators on this and when I go to monitor the correspondence tab is nice, slim, tidy, relevant, and useful.

    Emails that probably do not need to be filed:
    • “Happy Birthday to your administrative assistant!”
    • “Ordering pizza, do you prefer veg or meat?”
    • “Have a nice weekend!”
    • If I am sending my site PK tubes and I email them tracking information, then they write back to say they received the tubes, then I look in the lab database and see that indeed, they did complete the required PK draws, this conversation really does not need to be filed.

    Site Master File: Correspondence

    The Site Master File (SMF) or Regulatory Binder contains all of the essential documents to provide a record of study conduct. The SMF when reviewed with the clinical charts and archived study materials allows sponsors, auditors, regulators, and all other interested parties to reflect back on a clinical trial and understand how things were conducted, when, and by whom. The Regulatory Binder is created at the beginning of a study, updated as needed throughout, reconciled with the sponsor's Trial Master File (TMF) along the way during routine monitoring visits, and then archived at the end of the study.

    The SMF is usually a big chunky (broken) three ring binder (or series of many binders) stuffed to the gills, bulging at the seams, and typically just a little bit intimidating.
    Most sponsors maintain documents electronically but our industry is very much still a world of paper and at a site level, most study documentation is physical original or copied papers. For a list of the required items in a regulatory binder for a US trial please refer to ICH E6 Guidance Document on Good Clinical Practice (E6), Section 8 “Essential Documents for the Conduct of a Clinical Trial.” (protocol, Investigator's Brochure, trial logs, lab documentation, IP documents, correspondence, etc.).

    Today I am going to review the Correspondence section of the SMF and in a separate post provide some tips for monitoring this item. As a general rule, monitors do not enjoy reviewing the SMF; I would propose that the Correspondence section is one of the most detested sections and often skipped. I have seen correspondence that spans multiple volumes for longer trials and have personally lived the nightmare of organizing these on more occasions than I can count. Some people insist on filing every little stitch of paper but I encourage you to review the regulations, your company SOPs, and to file sparingly. Only file items that truly support the record of conduct and that tell the story of what happened, when, and by whom.

    What needs to be filed in Correspondence?
    Important emails/threads (As I discuss in a different post – not every email!), Note to File (sponsor/vendor generated), Official study memos, newsletters, Investigator Recruitment Plans, etc.

    If found in Correspondence, File Elsewhere:

    • Monitoring Visit Confirmation and Follow-Up letters (file these with the monitoring log or in their own tab for ease in reconciliation)
    • Budget/Contract, generally anything with $$$ listed
    • Duplicates (just shred the copy)
    • Audit reports
    • Training Files, agendas, and slide decks
    • IND Safety Reports
    • Investigational Product Documentation (packing lists, confirmation of receipt, destruction or return documents)
    • Packing slips (study supplies, lab supplies, etc.)
    • Subject identifying information (check-stubs for study participants, copies of IDs, medical records that have not been de-identified, etc.)
    • Notes to File (site generated) If subject-specific file with the chart, If more global in nature, just give them their own tab (ensure copies are retrieved and submitted to the TMF)
    How should correspondence be organized?
    Please file correspondence in reverse chronological order; old stuff at the back, new stuff on top, sorted by date.

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