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Saturday, December 6, 2008

You might be a CRA if...

So I am doing a little work this weekend and it reminded me of another email forward I received a while back so I am posting it for you all to enjoy:

You might be a CRA if....
1. You think working on weekends is normal.
2. You have ever used a bathroom on an change clothes.
3. Crying babies on an airplane don't wake you up.
4. You have enough frequent flyer miles and hotel points to take the entire State of Montana on a free vacation.
5. You can pack a week's worth of clothes in one suitcase.
6. Something beeps or rings on you when the plane lands.
7. Half of your voice messages are from recruiters.
8. You can survive on a diet of peanuts, pretzels and soda.
9. You can recite the ''airline safety speech'' verbatim.
10. You silently laugh to yourself when you hear someone at the Atlanta airport say ''I can't believe we are going to be late again.''
11. You belong to every frequent flyer program and frequent hotel guest program in North America.
12. When it is time for you to buy a new car you don't have to test drive any because you have rented every type of vehicle available.
13. You know the three letter code for at least 10 North American Airports.
14. When you check in to the hotel the desk attendant says ''Welcome Home.''
15. You spend more time at the airport than you do at your desk.
16. You have two checking accounts...One for your paycheck and one for your expense checks.
17. You change time zones at least 2 to 3 times a week.
18. You get up at 4am to catch a plane for a business trip.
19. You can identify every major US city from 30,000 night.

These had me in stitches but I can't immediately see the advantage of number 16. Please weigh in if it makes more sense to you. Let me know if you can think of a clever number 20 to add. I was thinking maybe something like "You know enough acronyms to create your own dictionary."

I promise to update the blog with more informative and topical posts just as soon as I get caught up with the stuff that pays the bills like finalizing monitoring visit reports and expense reports (I travelled 10 weeks straight with little to no home-office time) so please continue to be patient. ;)

Monday, December 1, 2008

Funny Things From Charts

Sitting in a room reading medical records can get a little dull but every now and then I come across an error or something that really makes me chuckle in the charts. A few weeks ago a co-monitor brought me a chart and pointed out this gem written during a Physical Exam: "Deaf in both eyes"

A friend forwarded me an email chain with some more so here is your chuckle for the day:

1. The patient refused an autopsy.

2. The patient has no previous history of suicides.

3. She stated that she had been constipated for most of her life, until she got a divorce.

4. Patient has chest pain if she lies on her left side for over a year.

5. On the second day, the knee was better, and on the third day it disappeared.

6. The patient is tearful and crying constantly. She also appears to be depressed.

7. Healthy appearing decrepit 69-year old male, mentally alert but forgetful.

8. She is numb from her toes down.

9. The skin was moist and dry.

10. Occasional, constant infrequent headaches.

11. Patient was alert and unresponsive.

12. Rectal examination revealed a normal size thyroid.

13. Both breasts are equal and reactive to light and accommodation.

14. Skin: somewhat pale but present.

15. Patient has two teenage children, but no other abnormalities.

Feel free to post a comment if you've come across anything just as silly - thanks!

Tuesday, November 25, 2008

Data Lock

Today we lock the database. Finally. I was brought on to this rescue study after conduct was complete; the other CRO had been fired and things were a total mess.  The final week was the longest yet, when I arrived on site there were still around 300 CRFs that had not been SDVd but luckily management sent in reinforcements. I was lucky enough to be joined by 2 excellent and experienced Senior CRAs and 1 very wonderful consultant CRA. It was a long week but the effort at my sites was extraordinary and we finished Thursday night ahead of schedule! We stayed late each night, I brought in lunch and caffeine so breaks were kept to a minimum, and I ran a lot of status reports and did a ton of cheer leading.

We tracked our progress on a white board and set and re-set achievable goals until all the work was complete. At the weekly sponsor call on Friday, everyone was singing our praises and stunned at the work we had done. My team assisted the site in resolving over 500 pending queries in around 3 days - a feat that nobody thought could be done so we surprised them all! I always was confident we would make the deadline because I had such a great team making the effort and the study staff was so motivated to meet the deadline. It was an eleventh hour delivery but we made it and we even beat some other sites to the finish line so that was satisfying, too!

I sent the other monitors home early and then stayed Friday organizing the source, pulling stickies and monitoring notes, giving everything a final glance, and helping the SC draft file notes. I also reviewed all of the ICFs one final time and ensured all the source was signed with complete headers. Everyone at the site pitched in to help and we had it all cleaned up in no time. I got home around 9pm on Friday night and spent the weekend watching TV and lounging around the house. I even booked a little trip for this weekend and then a mini-break in mid-December with some of my banked PTO. Now I just have to tackle my monitoring reports - yikes! ;)

I'm really happy with the site's performance at the end and the state of the source and the database now that we have locked. I'll return to my sites in January to perform the close-out visit and I'll inquire with the project team whether there are other sites that need a COV or monitoring support so I can help there as well. In any case, I'm eager for a little home office time to put my personal and professional life back in order - both have been on hold for about three months - but I'm so glad I had the opportunity to work on this exciting project. I like to think that you never get more than you can handle, and that the challenges along the way make the achievement at the end so much more rich and enjoyable.

I'll get back to posting here soon so please stay tuned and keep checking back. Thanks again for your continued interest!

Sunday, November 2, 2008

I'm alive

I've been getting a lot of emails and comments asking where I have been since August. I apologize for not posting (I have almost 40 topics begun/drafted but just haven't had time to pull the trigger on posting any of them!). For those of you that check back here often, I appreciate your interest and support and I promise to get back to posting soon. Several of you have posted and emailed me specific questions and I will address all of those as soon as possible. For today, however, just a quick explanation as to what I've been up to...

So here is my excuse, I have been assigned to a nightmare Phase II surgery study that was fully enrolled but looked like it might never lock so they ramped up on staff. At first I was just co-monitoring and helping others clean up their sites but (the reward for a job well down is always more work) I was eventually given two of the four worst sites to manage. I've been told this is a compliment and that management knew I could get the work done and salvage the data...but really though, I'm feeling like a sucker for accepting the assignment! In all seriousness, this study has been a great learning opportunity and I have grown a lot in just a few short months.

The good news is that my two sites are only about 1000 miles away and I have had no trouble getting direct and inexpensive flights. Of course they are in a different time zone, and I have basically been living at these sites (flying in on Sundays and coming home late Thursdays or Friday) and can barely remember what my own home looks like! One site lets me arrive around 7 in the morning and the other one locks me in at night and lets me stay as long as I want so that has made for some extremely long days. The bad news is that the protocol is complicated, there have been significant changes in staff and limited resourcing at both sites, PI oversight was generally lacking, subject charts are very very thick (they are hospitalized for about a week and then many subjects go to rehab), both of my sites enrolled subjects that were not eligible, neglected to report SAEs and AEs that are of special interest to the sponsor, performed major dosing errors, failed to adhere to the protocol (often times just neglecting to do entire procedures or study visits), and reported their errors inconsistently (or not at all) to both the sponsor and the IRB. I feel like I am missing something...ah yes, one of the sites was audited by the sponsor and shut down (too late in my opinion and of course now I have to prepare audit responses) but you get the idea - it is a total mess.

On a positive note, this study has excellent leadership and I have been learning a lot and becoming much more confident. I've even been getting lots of extra resources to help me get the job done. On any given week, I have up to 7 CRAs (many much more experienced and Senior than me) helping pour through the charts and finish the pending SDV. It has been fun to be in charge and even more fun to go to dinner and debrief with my fabulous colleagues. I'm so grateful for all the terrific help I have been sent but it has been an exhausting few months. Supposedly we will lock at the end of November...just in time for a PI sign-off at the holidays and that always goes so well (*wink wink*).

I still get contacted by recruiters at least 3 times a week (how do they even get your info?) but I'm really in a holding pattern right now and not looking to make a change. I've been with my CRO for a year and anytime I have gotten frustrated, overwhelmed, or cornered, my boss and Project Managers have always had my back and given me great support. I've built a pretty good reputation for myself as a top producer, eagerly accepting all assignments, highly organized, and extremely flexible in a dynamic environment. I've been chatting with my boss recently about my career development and possibly stepping into a Lead CRA role so I will keep everyone posted as things progress. Ah yes, and I will post more to my blog. Soon, I promise. ;)

Tuesday, August 19, 2008

Monitoring Visit: What to Pack

I came across a nice online article recently by Greig Waddell with tips on how to save time when traveling for business. Click here to check out the full article. I thought all of his points were great but I wanted to expand upon it a bit in the context of traveling to a monitoring visit.

So you are going on a monitoring visit. You want to dress sharp and have all the supplies you need. Choose clothes that you can mix and match, that you don't have to dryclean or iron, and that are professional and appropriate. I travel 2-4 days each week so I pretty much just keep my suitcase packed all the time and just replenish/rotate things out for cleaning as needed. This means two sets of toiletries, those I use at home, and those that always stay packed in my 3-1-1 TSA approved baggie. Staying "packed" has saved me on several early mornings when I haven't exactly given myself quite enough time to get up, get out of the house, and get to the airport. Here is a selection of my luggage:

No, I don't travel with 3 bags. Click here and then scroll over the photo at my Flickr site to learn more about what type of luggage I use for different length trips.
I don't check bags with the airlines, but if you do, don't check valuables like expensive jewelry or your laptop. Don't forget that sponsor proprietary information including protocols and regulatory documents are extremely valuable. If you can't carry all your documents, FedEx them to yourself, but NEVER check them because luggage can get lost.

I try to carry as little paper as possible - if the sponsor doesn't provide you with a pocket sized spiral-bound protocol book, Kinkos or a similar copy center will make you one for less than $50 and you'll be glad to have it plus you can probably get reimbursed for it on your expense report (check with your lead first). Remember that you may need to retrieve copies of documents at the site so bring some kind of inflexible folder so they won't get damaged or bent in transport. Other documents I like to bring electronically or carry with me (good to review on the airplane) include the MV Checklist, study contact list, print-outs from the IVRS, and old monitoring visit reports/pending action item lists. So you can follow the links below to find out more about what is in my bag:

More details and photo notes available at my Flickr page.
Click here for a copy of a printable checklist that helps me pack for monitoring trip. It is in MS Word so you can download it and edit to your specifications. Send me an email if you have any trouble downloading the document and I will forward you a copy.

Please also check out my travel tips section for more info.

Sunday, August 3, 2008

Efficiency Tips: Spend less time on Expense Reports

I pay for most things with my American Express (Amex) but I am required to submit receipts for all charges over $10. We either scan our receipts in and attach them through the web browser to a pending report or we fax them to a dedicated fax # with a spiffy system-generated coversheet that accomplishes the same thing. In the expense system website, every few days, charges from the Amex are automatically available for me to add details to (which sponsor is the charge billable to? is any part of the charge non-billable?) and to group into pending expense reports. Unfortunately cash purchases or those made on my personal credit card have to be manually entered and categorized so I try to limit these types of transactions.

I make my own travel arrangements through our travel agency and they pass those charges through to my Amex. Airline tickets, rental cars, and hotels are the bulk of my expenses and whether or not they are reimbursable is very clearly delineated in our travel policy (for example, a $500/nt stay with spa treatment at the Ritz is not OK, but $150 at the Marriott with free breakfast is very much within policy). There are also clear guidelines for our meal expenses and tips in the travel policy too, but in my experience, this is the area where I most frequently have issues with reimbursement. Part of the problem is that I may lose a receipt or they haven't scanned in clearly so my entire expense report can get denied or otherwise held up in processing. For that reason, I typically submit 2 expense reports for every trip. If I have booked airfare more than 2 weeks in advance, that goes through in its own report so I can go ahead and have the company pay my Amex down before 30 days pass. Everything else I pass through up to 4 weeks after the trip in a second expense report.

While traveling and at the time of purchase, I usually slip charge receipts in the billfold portion of my wallet but after a few days the wallet is overstuffed and won't fold closed. A solution I have come up with is to periodically group and file the receipts in a specific pocket of my laptop bag. The keycard folios they give you at the hotel are terrific for organizing receipts so I simply group them together in chronological order in those handy little keycard envelopes. I organize in two categories, transportation related (receipts for gas, rental car, parking, cabs, valet, tolls, etc.) and for meal expenses and tips.

Efficiency: Eating breakfast and working on expense reports.
When I am flying home from my visit, I put down my tray table and prepare all the receipts for scanning. I now travel with blank paper and tape (tape dispensers are bulky so I have taken to carrying self-dispensing double sided sticky crafting squares. I get mine from the dollar store but click here for a link to the product I am using). I fashion all the receipts on as many pages as I need and when I get home it only takes a few minutes to scan the whole stack and attach them to my expense report. Many hotels offer free business centers with scanning and faxing so I could also do this on the road but I like to do it when I get home for now.

Timesheets are due every two weeks so I ensure that when I am signing off on my timesheet I am also submitting any pending expense reports. Our Amex is paid bi-monthly so this helps me to always be current and never go in arrears on my corporate account. You certainly don't look very professional if you aren't paying your credit card on time so I manage this closely. Not to mention, who can afford all the crazy fees they would love to charge you?

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Efficiency Tips: Spend less time on your Timesheet

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

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

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

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

Efficiency Tips: Spend less time on Monitoring Visit Reports

As a monitor, you may visit several different study sites in a single week and possibly for different protocols. I often find when I get home from a trip like that it is hard to write my report and keep the details of the different sites straight. One thing I have done to successfully overcome that is to draft my report before I even do the visit. On most studies, your Lead will provide you with a template report that you will need to complete following each visit type. You might also use an electronic system to create your reports but luckily, mine are usually just MS Word templates. Every report is guaranteed to have a header section that includes the MD name, facility name and address, visit type, visit date, date of last visit, and list of attendees. You probably know all of this information before you step foot on the site so just fill it in before you go.

Things I am unsure about I highlight in yellow so I remember to return to them later. Unless this is your first visit to the site, chances are there is a previous report completed by either you or another CRA that has items that probably need to be carried over to your current report. You will want to refer to your company's SOPs and your project-specific monitoring plan to know which items get carried forward. On some of my recent reports, this has included Enrollment data (I can usually get the current number of Screened, Screen Failed, Enrolled, Early Term, and Completed subjects from the IVRS system before I even show up for the visit), summaries of Protocol Deviations to date (they stay on the report until the IRB acknowledges receipt of the deviation), SAEs that are not resolved, Regulatory Documents that need to be collected, and pending Action Items or those that have been resolved since the last report date.

Drafting your report before the visit has the added benefit of helping you write your confirmation letter and get a grasp on what activities need to take place during the visit. You will be organized before you get there and more likely to monitor efficiently if you know exactly what is outstanding.

While you are at the site, avoid keeping notes on notebook paper; just write pending items directly into the Action Items or other applicable section of your report. If the items you notes are resolved by the time you leave you may decide to dump them from your report (depending on how much detail your company/sponsor is looking for) and if not, mark them pending and submit them as part of your draft.

When I am at the airport waiting for my flight to board, I can usually knock off a draft report in about 20-30 minutes. Then when I have internet access, I just submit it and forget it (or at least until I get a revisions request)! What efficiency tips work for you?

Not getting any work done in the airport terminal?
Your company may reimburse you for airport lounge
access or you can typically get a discount pass through
loyalty to an airline or credit card offers.  In the lounge
you can be productive, enjoy snacks and beverages,
access the internet and a business center plus plug
in all of your devices.  

Efficiency Tips: General and Administrative Duties

I work at a CRO so we have a fairly robust on-line expense reporting system and a thorough web-based system for reporting our billable and non-billable time through an interactive on-line timesheet. Well, I don't have the new iPhone and we still can't access the internet while in-flight so I am not exactly on-line all the time. The result of this is that I have a tendency to get behind in both my expense reports and time reporting.

Complete administrative tasks
while on the road by booking
hotels that have well-appointed
business centers. Internet access,
printing, copying, faxing, scanning,
and a FedEx drop are a major help.
Timely reporting of billable hours and submission of accurate expense reports are two of the main conditions of my employment. My other big responsibilities are showing up when and where I am supposed to for site visits/teleconferences (that includes making travel arrangements far enough in advance that I am getting the best fares and being cost-conscious for my company and the study sponsor) and getting my reports done on time. I'm never actually late with reports, timesheets, or expense reports, but at times, I have felt like I was not always as on top of it as I would like to have been.

For each of these job responsibilties I have a few tips that have helped me stay under the radar of the big bosses and consistently make my submissions accurately and on-time. I'm always on the lookout for new methods of reducing my workload and working more efficiently, so feel free to post a comment with other suggestions. This is a big topic and I have a lot to say so I will tackle it in three different posts: MV Reports, Timesheets, and Expense Reports

I hope you find this series helpful!

Thursday, July 10, 2008

Less schwag? How much less?

Just checked out a news article from The Pharmaceutical Research and Manufacturers of America (PhRMA):

It seems that new regulations (regulations to which drug manufacturers may or may not voluntarily adhere) will limit the goodies that sales reps can give to MDs in their sales calls. Reps can still bring in small meals but are asked not to give mugs, pens, and other items that have no "educational value".

From the article, it seems that this is a consumer driven new policy. The idea being that patients go to their doctor and they see all the brightly colored tissue boxes, posters, and beanies with spinning tops (ok, I have no proof that reps are giving these out....) all with the logo of some fancy designer drug plastered on the side and begin to wonder if their MD has their best interest at heart or whether they are simply on the payroll for the Pharma companies. It is getting harder and harder to trust the good ole' doctor these days.

Overall the changes sound good but because the regulations are voluntary and sales reps are so clever at working around and bending the rules, it will be interesting to see if and how the landscape of pharmaceutical detailing changes in 2009. PhRMA will post a list of participating manufacturers on their website -- at least 3 biggies have already signed on. I would love to hear your comments on the topic.

Wednesday, July 9, 2008

Close-Out Visits

I've done about 10 close-out visits in the last few months so it feels like a good time to write a short article explaining what the objectives of these visits are and how a typical close-out visit (COV) is conducted.

A COV will occur once subjects are no longer being dosed, all the data have been collected (there are no more outstanding AEs/SAEs & all outstanding Queries/data clarification forms have been resolved appropriately), the database is locked and ready for statistical analysis, and the study conduct has ended. At this point, the site's contributions are over so the monitor returns for one final visit to shut down the site. The whole concept behind a close-out visit is to ensure that everything is neat and tidy at the study site and that the documentation is well organized and will remain intact and be accessible in the future as needed for regulatory reasons. A sponsor or the FDA should be able to return to the place of study conduct years later and re-create exactly what occurred at all points during the trial by reviewing the regulatory documentation, subject and source documentation, full medical charts, and any other applicable study records. Documentation is everything in our industry and we are always saying, "if it isn't documented it didn't happen." If thorough and accurate records are not maintained, the PI cannot prove that the study was conducted in accordance with the protocol and all applicable regulations and that subject safety was adequately monitored throughout the conduct of the trial.

Site Supplies and Drug Return

We are using tamper evident tape to
box up investigational product for return.
If the tape is lifted it leaves behind an
artifact to show it has been tampered with.
One of your major objectives at the COV will be to assist the site in dealing with any unneeded study materials or supplies. With permission from the sponsor, some of these activities can even take place before the close-out visit as you remotely supervise. The close-out duties will likely include disposing of or retrieving all unused lab or study supplies such as patient handouts, electronic diaries, etc. In most cases, you will have the site generate a file note or similar documentation so there is a record indicating that study supplies were disposed of or moved off-site. 9 times out of 10, the Investigational Product (unused and the used packaging) will need to be inventoried, accounted for in drug logs, and then shipped to a depot or destruction facility. Sometimes the drug will be destroyed on site by a pharmacist or according to the site's SOP but this is really the decision of the sponsor. If you are lucky, you were able to pack up and ship back drug routinely throughout conduct otherwise you will have to deal with it all at the end.

Essential Documents
You will have the PI sign off on any tracking logs that were used during the study. The original will be placed in the site's Regulatory binder but you will retrieve a copy for the Trial Master File. You will ensure that a Subject Identity List was completed and will be kept that lists the contact information for all treated subjects (you will not take a copy of this document as it has private information and stays at the site only). Documents you will take copies of include: Site Visit Log, Subject Screening AND Enrollment Log, Delegation of Authority Log, Proof of Drug Receipt, Subject Specific Investigational Product (IP) Accountability Logs, Copies of temperature/freezer logs, Site Initiation Statement, Training Documentation, Overall Site IP Log, Protocol/Amendment Signature Pages, Any updated 1572s, medical licenses, or CVs, Site communications to the IRB/IEC (ethic committee), and the IRB Final Status Document. Obviously in a study with many safety reports, a long line of routine monitoring visits, multiple site hand-offs/transitions between several different monitors, or a slew of important correspondence, checking that the essential documents binder(s) is in perfect order can be a time-consuming task.

Subject Records
Although you will have already verified this throughout conduct, the close-out visit is your last opportunity to be absolutely sure that the appropriate version of signed and dated Informed Consent Forms are on file for every subject. You will also check that all source is complete (all lab reports and ECGs have been signed and dated with Clinical Significance assessed by the PI/Sub-I) and that all AEs/SAEs have been signed off by the PI/Sub-I and that they were followed to resolution as specified by the protocol. Finally, check that all significant Protocol Deviations (study procedures not conducted according to protocol, enrollment of inappropriate subjects, dosing errors, consenting errors, unblinding, subjects developing withdrawal criteria yet continuing in study, etc.) have been properly recorded and the sponsor/IRB has been notified as appropriate.

PI Responsibilities
Discuss with the PI his/her responsibilities including: query/data collection following the close-out visit, essential document retention, publication rights, and the necessity to update the Financial Disclosure statement if there are changes in their financial interest for up to one year following completion of the study. Finally, explain to the PI the potential for regulatory agency inspection and the requirement that the site notify the CRO/sponsor immediately if contacted for an audit/inspection.

Assuming you have done a thorough job in monitoring throughout conduct, the COV should be a relatively short-visit. Meeting with the PI to discuss their regulatory responsibilities post trial conduct and obtaining required signatures usually takes less than 20 minutes assuming they are an experienced investigator and are already familiar with the GCP schpeel. Drug return often takes several hours but you can prepare most drug return documents in advance of the visit by using sponsor or IVRS reports and usually save a considerable amount of time on-site. You should have been reviewing the regulatory binder at every visit throughout conduct so it should really be in order at this point and stuffed to the brim - I usually budget no more than an hour to ensuring that the binder is complete.

After you complete the close-out visit, you will write a report to the sponsor to let them know that all of the objectives were completed and a follow-up letter to the site thanking them for their participation and informing them that there are no further pending action items. Any new regulatory documentation you copied while on site will need to be forwarded to the Trial Master File so that the sponsor's documentation is a true mirror of what is on site.

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Thursday, June 5, 2008

Who's running this study?

I just received an interesting article from a colleague:
The article discusses a clinical research unit in Florida where the PI oversight isn't exactly verifiable. This is always an issue for us as monitors, especially when the Dr. practices from one location and the study is conducted in another. I apply extra scrutiny in this case to ensure everything is in order and that the data isn't "too perfect" (do the subjects even exist? qualify? are they being followed properly as per protocol?, etc.)

As a monitor, I always like to have the sponsor pin down (before conduct begins) exactly which actions can be delegated (lab draws, EKG, etc) and which actions must be reserved for the PI or medically licensed personnel. In many studies, the assessment of Inclusion/Exclusion Criteria, Physical Exams, Dose escalations/de-escalations, and Lab/safety reviews are responsibilities that must be reserved for the physician. It is best if this is written in a statement on the Delegation of Authority Log but I take what I can get and always include this as a topic at site selection and initiation visits.

I always prefer to work with sites where the PI is highly involved but as monitors we don't always get that choice and the quality of the data can suffer. However, I recently worked with a site that enrolled almost 30 subjects in one month. They were the highest enroller and the numbers shocked everyone -- I immediately suspected that the PI may not have been very involved in the conduct due to the volume and time commitment that would require. The site had been initiated at the IM so by the time I had my first visit, they had enrolled over 10 subjects in this 7 week study. I conducted 4 routine monitoring visits over the 2 months and even brought co-monitors with me to handle the volume and "sniff out the deficiencies". At each visit the PI was available and very informed about his subjects and was constantly asking me to go back to the sponsor for clarifications on the protocol and to discuss changes he witnessed in his patient's lab values. My instincts were good but the reality is this PI was also very good and very involved in the oversight and conduct of the trial so I had nothing to worry about after all. The site was organized, fast at CRF entry/query resolution, and thorough. I would work with the site again in a heartbeat. That just goes to show that you don't always have to compromise quality when you have quantity.

On the other hand, I had a few other high enrollers in this study where PI oversight would have gone a long way to improving conduct. So the takeaway here is be especially wary when the PI is MIA and you have an over-zealous coordinators who always reassures you that "it's fine" ,"I'm handling it", "oh really, I didn't realize the protocol meant it that way..." and other red flag statements. Make sure the PI is available to meet with you at every visit. If you have had 2 visits in a row where the PI isn't around, escalate it to your lead CRA or the sponsor or refer to your SOPs. When an investigator signs a 1572, that is a legal contract that they agree to personally oversee the conduct of the trial. If you aren't satisfied that this is happening, document it in your report and follow-up via phone or meet with the PI to discuss your concerns. It is an uncomfortable conversation but that is one of your responsibilities as a monitor. I know from experience that this conversation is easier to have in the beginning rather than at the last visit before data lock, or when it is time to sign off on the casebook, or even after a (gulp) sponsor or FDA audit.

Sunday, March 16, 2008

Routine Monitoring Visits

Routine or Interim Monitoring visits are basically any visit that occurs after the site is initiated and up until the site is closed out. As monitors, we visit our sites periodically to ensure that they are compliant with all the regulations, subject safety is being adequately followed, data is being captured in a timely and reliable manner, the Investigational Product is being handled as per protocol and relevant regulations/guidelines, there are no significant deviations from the planned study protocol, all important study documentation is being generated and stored properly, and that the research site is adequately supplied in regards to lab kits and other pertinent study materials. The ultimate purpose of our job is to protect subject safety by monitoring the trial conduct for ICH/GCP compliance.

When planning your monitoring visits
it is helpful to have a reasonable expectation
of how think the medical records and source
documents will be. Know in advance how much
you will need to review so you budget enough
time to successfully complete your objectives.
Your agenda from visit to visit may vary slightly based on the length of the study and how many times you plan to visit, the amount of time you spend to plan at the site for this particular visit, the site's progress to date (if a site has yet to enroll any subjects you surely won't have any CRFs to review or pull), and where you are at with the general monitoring plan (for example, drug accountability may be done all along or just at close-out).

Prior to your visit you will contact the site to set up a suitable time for your visit. Visits typically last a day or two. Ideally, the PI would be available to meet with you during the visit. You will send a confirmation letter to the site once a date is set (be sure to confirm the address before you go if you haven't been there before!). More often than not, your study lead will provide you with a monitoring visit checklist or at the very least, a monitoring report template so you will know exactly what tasks you are expected to perform on-site and what topics to cover. Here are some of the specific tasks that are routinely performed at these visits:
  1. Informed Consent Form (ICF) review: You are ensuring that every subject was adequately informed and consented to the study before any study procedures were completed (I recommend checking lab draw times and ECG times - if required at the screening visit - against the consent time to be extra sure that the consent was the first study procedure to occur). There are other state specific regulations you will need to know and monitor for. For example, in some states subjects must be 19 to participate and in California every subject must sign the 'CA Bill of Rights' document, etc. Sometimes there are multiple versions of a consent due to a change in the facility address or the details of the protocol. Ensure that all subjects signed on an IRB approved version (each page will be stamped in the upper right hand corner and the version date will be printed on each page). Proper consenting of subjects is critical to ensure the security and privacy of health data and that subjects are adequately informed of the study procedures, risks and, benefits. If the consent is not signed or properly completed inform the Study Coordinator and do not review this subject's medical chart until consent has been properly obtained.
  2. Check for Serious Adverse Events (SAEs): Per the guidelines, an SAE is any untoward event that results in death, prolonged or new hospitalization (longer than 24hrs), significant disability, or congenital anomaly (birth defect). If the event has not been reported, assist the Study Coordinator in doing so and inform the sponsor immediately.
  3. Review Protocol Compliance: In your chart and source document review, you can verify that subjects were sign at the right times and the right procedures were conducted as per the protocol. You will have study-specific procedures for reporting deviations. Deviations of a serious nature may be reported in an expedited manner and may need to go to the IRB (dosing errors, unblinding of study treatment, subject enrolled that did not satisfy entry criteria, etc.)
  4. Compare source documents to Case Report Forms: You are checking that the data in the chart matches the Case Report Forms (which will be later entered into the clinical database and combined with other subject's data to complete the safety and efficacy analysis for the Investigational Product). Determine whether or not CRFS being completed in a timely manner. You also want to verify that the source is complete, neat (all corrections must be compliant with the regulations - white-out is not OK), attributable (who wrote it? Is it initialed and dated), contemporaneous (was it written at the time the procedure was completed?), valid (is the data collected even possible?), etc. Sometimes you will be asked to pull the case report forms and send them in to data management and other times they will stay at the site until the end of the study.
  5. Review Investigational Product (IP): The study protocol will explain how the IP is to be stored, dispensed, and returned. Verify that all of this occurred properly by reviewing temperature logs, storage facilities, administration records, IVRS entries/reports for subject-specific IP accountability, and speaking to the relevant personnel.
  6. Regulatory Binder / Essential Documents Review: Determine if any forms need to be updated or pulled for the Trial Master File (TMF). The TMF is meant to be an exact replica of all the documentation at the site. Specific information regarding the contents of the essential documents binder are covered in section 8 of the guidelines.
  7. Confirm Site Adequacy / Site Status: Determine if there are new staff at the site or if staff have left. Can the site manage with current staff? Has the site or the lab moved? Confirm that there are adequate study supplies
  8. Study-Specific Monitoring Tasks: Depending on the protocol, you may need to perform additional tasks such as shipping materials back to headquarters (for example lab specimens, xrays, etc.), calibrating or reviewing calibrations of equipment, site training, checking eDiary compliance, etc.
  9. Review Ongoing or Pending Issues from Previous Visits: At some point during every visit work with the staff to resolve any items identified at previous visits as ongoing issues. Indicate in your report once these are resolved.
  10. Review of findings with the site: Whether or not you find issues during your visit, keep the site staff posted on your progress and how things are going. Especially, if the Principal Investigator is not available during the visit, be sure to summarize everything accurately and completely in your follow-up letter.
Try to schedule your next (or next several) visits before you leave the site. After the visit, write your report and send the follow-up letter within a week or per your monitoring plan and refer to your company's SOPs. Always report significant compliance issues to your management, the sponsor, IRB, and QA as appropriate. Remember that you must document everything because of the adage, "if it isn't documented, it didn't happen". Please contact me if I can elaborate on anything or if you think I've left something important out.

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Saturday, February 16, 2008

Tips for Frequent Travelers

So I have already written to you about travel safety, and now I am going to write about some travel perks; mainly hotel points and airline miles. It is to your benefit when traveling for business to accrue some rewards for yourself. First you will want to obtain and read a copy of your company's travel policy so you know where they can flex and where you will need to flex. For example, my company requires me to book through their travel agent and we have preferred hotels and a preferred rental car company. I must pay for everything with my corporate Amex and then be reimbursed (so other loyalty Credit Cards are not an option) but I can (and do) add Membership Rewards to my Amex account for $75 a year and collect membership rewards points for every dollar of my employer's money I spend on travel to and from sites.

I spend a lot of time on airplanes and
collecting reward miles is a real perk
that I can use to obtain discounted or free
 leisure travel.
In regards to airfares, it is wide open so I can research and communicate to the travel agent which fares I want provided they are within the travel policy guidelines. In this way, I can maximize my reward points and choose to focus my reward accruing efforts on a preferred airline/chain so I can rack up miles/status/points for leisure travel. Be careful of diversifying too much or you will only achieve a low level of status/rewards in many programs whereas it is typically better to have a lot of status/rewards in just a few programs. This is less flexible but in general, you will see greater returns when you focus your efforts.

I was first going to attempt to download all the tidbits I have learned over the years but then decided a list of my favorite web links would be much more effective.

Find the Lowest Airfares

  • ita software - Click on the graphic in the lower left called 'Search Fares using QPX'. Be exact with your entry as this system can't really 'guess' at what you want. When your results come up use the third toggle button at the top to 'choose flights (graphical)' Now you can sort and stack and filter or just choose one segment at a time. I love this site! The only airline I have found not listed so far is SW so I just check them separately.
  • - Another price aggregator as above.
  • - Will the fare be cheaper if you wait until next week to book it? This site tells you!
  • - Tag a fare and book it once it is cheaper. If the fare does drop after you already booked (assuming you booked directly through the sirline website) you might be entitled to a refund or future credit thanks to the low fare guarantee).
  • Many airlines will give you bonus miles for booking through their site. I can't do this because we are required to use the agency but this is especially powerful when you own and book with their co-branded credit cards. Something to look into...

Booking Hotels

  • Again, pick one or two chains and accrue status so you get upgraded rooms and executive lounge access, free breakfast, bonuses, etc. Plus, once you are at the higher tiers you typically accrue points faster. This chart is helpful for comparing the different loyalty programs - thanks Starwood Preferred Guest program!
  • One more tip here, once you get high level status in one program call competing programs and ask them to 'status match' or to allow you to 'challenge' the high tiers of their loyalty programs. These promotions are usually offered in the first half of the year. Airlines will status match, too -- never hurts to ask, anyway!


  • - Make informed decisions when choosing your seat - make sure your seat fully reclines and that it doesn't have a blocked view of the TV or limited space.
  • - How many seats are left in each class of service on a plane. Helpful when you are hoping for operational or status based upgrades to a higher class cabin or if you are looking to get bumped (sometimes you can plan to miss a flight because you will be compensated with a free roundtrip US ticket or a discount voucher for future travel).
  • - An ever-changing Wiki that has aggregated information about traveling and loyalty programs. Companion website to flyertalk, see below.
  • - This is an online forum with lots of frequent travelers who share their tips. I subscribe to posts and threads and I get these emailed to me weekly. I download my email to a local client so I can browse through them in digest format while on my frequent flights. I have learned so much here and love this free site.

Tools for Tracking Points and Miles

  • I prefer a web-based program so I can recommend the following: (this site is free to try for 30 days and then $14.95 annually. It has rewards summaries but also lets you know which accounts are about to expire, and my favorite part is the 'Elite status summary' which tells you what you need to earn to get to the next Elite level in any given program.)
  • (this site is free and will also manage your personal finances and help you set budget goals or you can just add your reward programs and have it manage those exclusively. Of note, your bank might already subscribe to this service for you as some major financial institutions like Bank of America, Fidelity, and Wachovia do... Check here)

Shoot me an email or leave me a comment if something important is missing from this post or you have more questions about this topic that I can answer. I would also love to hear your tips and success stories so feel free to leave those comments as well!
Read more about What to Pack in this post.

Tuesday, February 12, 2008

Clinical Fraud Hearing Held Today

I received an email from my old boss today alerting me to an interesting webinar. I am posting it for other people's benefit. She states "The webcast below is a hearing to explore fraud at a clinical site for a study conducted by Sanofi-Aventis. The hearing took place this morning. Interestingly, the CRO and the CRA who monitored the site are among the witnesses..."

from the webinar site:
"Ketek Clinical Study Fraud: What Did Aventis Know?
The House Energy and Commerce committee’s subcommittee on oversight and investigations will hold a hearing at 11 a.m. EST to explore what Sanofi-Aventis knew about the problems with clinical trials for its Ketek antibiotic. Last February, the FDA withdrew approval for two of three uses for the drug, and issued a Black Box warning for use in treating community-acquired pneumonia, which was issued in the wake of numerous Ketek patients suffering 93 adverse events, including 12 deaths.

Among the witnesses will be Chuck Grassley, the US Senator from Iowa, and Ann Marie Cisneros served as a clinical research associate for PPDI, a contract research organization that conducts clinical trials on behalf of drug sponsors. Last February, Cisneros appeared at a hearing held by the same committee focusing on the FDA’s failure to ensure safe prescription drugs. Cisneros testified that Aventis knew of fraudulent clinical trial data involving Ketek, but that the company chose to ignore it."

Go here to watch an archived webcast

Feel free to comment on this post or shoot me an email if you have any thoughts or additional questions.

Friday, February 8, 2008

What to Expect at a CRA Interview

I’m posting to let you know what kinds of questions you might expect to be asked during a CRA interview. Practice these in the shower, in front of the mirror, or with a friend so you are prepared!

Typical Questions
Here are general questions that you will likely be asked with tips for answering shown in italics:
  • Tell me about yourself? Keep it short and hand them a copy of your resume to look at while you give the penny-tour of your background and experience. Showcase yourself, “I live in San Francisco and I have 5+ years experience in this industry. I have been working as a CRA for over 18 months. I have had the opportunity to work in Phase I, II, and III trials for the following indications… I attended courses for CRA training through a local university and I am an active ACRP member.” Be prepared to explain why you are currently job seeking and any gaps in your employment history or a trail of many past job over a short period of time.
  • What are your salary requirements? I’ve had success with this script, “I will consider the entire package including employer flexibility, 401K, a competitive benefit package, etc. However, my minimum salary requirement is $$$$. I would be pleased by a compensation package that includes benefits and incentive compensation to increase the value. From my research, it appears that similar positions in this industry are paying between $$$$ to $$$$.” Then be quiet!!!
  • What percentage/amount of time are you willing to travel? Be honest. Travel is difficult and it is not in yours or the employer’s best interest for you to misrepresent yourself when this question is asked.
So here are the more role-specific questions:
  • Have you had GCP training or formal CRA training through an employer or accredited course?
  • Do you have experience with the following?
    o Regulatory document review
    o Selecting and recruiting qualified and interested investigators
    o Performing source document verification
    o Utilizing EDC, electronic diaries, or IVRS systems
    o Database close
    o Development of protocols or ICF?
  • Do you have experience with the following therapeutic areas: Cardiovascular, CNS, Oncology, Diabetes, HIV, etc.? If you are interviewing with a CRO this is especially important because they will need to market you internally and to clients. There is no sense in lying here because there is no substitute for experience. Try to highlight experiences you have from other jobs that better prepare you for a monitoring role. For example: “Although my oncology experience at this point has been limited to clinical database and CRF design, that experience has afforded me the opportunity to read through no fewer than 10 to 15 different oncology protocols from a variety of sponsors and assist (at least on the data end) in these sorts of trials. I have had the opportunity to develop some very fundamental and transferable skills in XYZ indication this past year related to study start-up, maintenance, building/maintaining relationships with study sites, trial fiscal management, and facilitating cross-functional trial specific working teams to track and deliver important study milestones on time/budget.”
  • What is the greatest number of [protocols, sites, patients] that you have been responsible for at any one time?
  • Which phases have you worked in?
  • How many [pre-study qualification visits, site initiation visits, site monitoring visits, site close-out visits] have you conducted in your career?
Undoubtedly, the last question you will be asked is, "Do you have any questions for me or about our company?" And the answer is, Yes, you do! I know you will be nervous, but ask good questions and listen to the answers to the questions and try to get feedback during the interview so you know how you are doing.  You may have been misunderstood during the interview or missed an opportunity to really sell yourself.  Asking great questions will give you one last chance to show your best or address any concerns the interviewer has before you part or even in a follow-up letter or email.  Here are some generic ones, but you have to ask something:
  • Describe the three top challenges that I'll face in this job?
  • What are the key metrics for measuring success in this position?
  • If I were offered the opportunity to work with your organization, what would you like me to accomplish in my first 90 days?
  • How would you describe the qualities of the most successful people at your company?
  • How closely do my qualifications match the requirements for the open position?
Interview Styles
At this point, I want to mention that there are various interview styles. Being familiar with how (and why) questions might be asked will only help make you more prepared when it is time to come up with the answers. I am going to discuss a few interview styles below. The person conducting the interview may stick to just one style or have a mix of several – this is especially true when you are in a panel interview. Then it feels like you are in a firing range but just stay calm and try to engage the panel so you aren’t doing all the talking. After all, this is your opportunity to interview them, too, right? Anyway, here are a few interview styles you might encounter:

Behavioral – Everyone knows that past behavior is a very good indicator of future performance. This interview style will require you to answer in a manner that shows you are creative and quick on your feet. Sometimes the right answer is not as important as the delivery. Before you answer think hard about why they are asking this particular question and try to cite examples of past behaviors that are relevant to the job you are applying for and explain at the end how the skills and experience you are describing would be transferable in your new role. If they ask you about a past mistake or you describe something you did but would now do differently, say so and explain why. Nobody is perfect so showing that you learn from past experiences can only help you in the interview.
  • Tell me about a time when you showed your ability to [adapt to a new situation, solve a problem, etc.].
  • Tell me about a time when you demonstrated [initiative, integrity, excellent communication, etc.].
Situational/Scenario – If you have no idea what the right answer is, you can try stalling, asking the interviewer for help, or just qualifying your response. For example, “Honestly, I am thinking of a few possible answers for the question. On the one hand, I feel like this might be the right response, but on the other hand, I can see a scenario where this might be the right approach. Which are you looking for?” or “Well, I must admit that I haven’t ever been faced with this particular situation, but I imagine I would handle it as follows….” Here are some examples of situational questions:
  • You’re at a site and discover an unreported SAE, what would you do?
  • You are performing a routine monitoring visit and discover that the site has enrolled a subject but forgot or improperly consented them, how would you handle this situation?
Assertive – I personally find this style offensive. Any employer that utilizes these tactics is likely not one that I am very interested in working for. After all, if they are a jerk in the interview, what is it going to be like on a daily basis or when it is time to sign your expense reports, or partner to work on your performance goals, etc. In any case, an assertive interviewer will treat you really nastily or act very cold/aloof to see if you will get nervous or flustered. I find brevity is key in these types of interviews and if there are long periods of silence, just sit calmly and pretend like you are unaffected. Be careful not to be too defensive – it is usually a trap to see if you can keep your cool under pressure. They might say something catty like:
  • It sounds like you don’t have a lot of experience with [insert something rude here], what makes you think you can do this job?
  • I have a lot of other more qualified candidates, why should I hire you?
Structured – This interview is basically just like a test and you need to pass to make it to the next round. It is a typical style for CROs (where many different people perform new candidate interviews but then need to assess all applicants against the same standards) or for first-round interviewers. Essentially, the interviewer is looking for a specific answer, and once you say the magic word or list the 3 bullets they are looking for, they will move on to the next question. It is fine to ask how you are doing if you are feeling nervous along the way – they will probably find it endearing rather than count that against you (they probably suffered through the same type of interview when they were hired).
  • What are the critical components of an ICF document? Know your regulations and GCP guidelines – All of them – this one is CFR 21 Part 50.
  • What are the activities that take place during an [initiation visit, close out visit, etc.]?
Every person you interact with may be
asked to provide input on your interview
performance.  Remember to always respect
"gate-keepers" like reception/administrative
staff and the HR person who arranged
the interview.
Here are a few other random tidbits of general interview advice:
  • Show up on time, be well-dressed/groomed, and be nice to the receptionist.
  • Fill out the employment application in advance. When you ask for this you are demonstrating your enthusiasm for the position and you are showing how organized and methodical you are when approaching new situations. If there is no application to be completed, at least bring your government issued ID and a list of references and old employers in case this is needed.
  • Avoid sounding cocky, smug, or coming off as entitled.
  • Assess how the interview is going by using any of these targeted questions after you provide an answer: “Did I give you enough detail?”, “Was I clear on that?”, or “Would you like me to elaborate?”
  • Never ever ever lie about your experience! Our industry is a small one and your reputation will precede you. It is a huge risk so just avoid it. Besides, as CRAs our primary objective is to ensure the safety of subjects exposed to Investigational Product. As an extreme example, if you lack the experience to do something and say that you actually can, you may be given a position that you are not qualified for and as a consequence, subject safety could be jeopardized.
  • Never say anything nasty about a previous co-worker or employer – it only makes you look bad.
  • Watch for and avoid illegal questions – It is absolutely inappropriate (and in some cases against the employment laws) for the interviewer to ask you questions about your age, race, religion, marital status, and whether or not you have kids. If you choose to volunteer this information in the course of an interview, fine. However, if you are queried about any of the items above just say politely, “I’m sorry, I don’t feel comfortable with that question but would be happy to address any others you have.” or re-direct the questioning in some other tactful way.
  • At the end of the interview thank them for their time, ask what the next steps are in the process, and ask for the job! I know it sounds silly, but 90% of applicants won’t ask for the job. You don’t need to be shy. You researched this company for weeks, you got all dressed up and took an entire day (or several) to come in and interview. You don’t need to dance around why you are there, “When can I start?”
Now you know what kinds of interview questions to expect but this is really putting the cart before the horse because we haven’t even scratched the surface of how to execute a sound job search. I will be posting in the future with more information that will make you better prepared for your new CRA role including: ‘Choosing the Right Company as Your New Employer’; ‘Networking’; ‘Doing Your Homework Before an Interview’; ‘Following up After the Interview’; and ‘Tips For Excelling in your First 90 Days of Employment’. Let me know if there are other topics that are of interest and I will be sure to address them in other future posts.

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Saturday, February 2, 2008

Home from the Investigator's Meeting

I've been assigned another study and attended a kickoff and Investigator Meeting on the East Coast last week. As I mentioned in my last post, an Investigator's Meeting is basically a chance to get all the doctors and staff together at one venue with the sponsor (usually a fancy hotel or somewhere fun) so that all the details of the study protocol can be reviewed and everyone's questions get answered. Also, because a lot of money is spent at these meetings to woo, wine, and dine the Principal Investigators (PIs), the meeting has the bonus effect of getting everyone psyched up and excited/competitive about enrolling in the study.

For my new study (it is a high cholesterol drug therapy study) I will have 11 sites each of which needs to be visited at least every 4 weeks depending on enrollment. There are 60 PIs total and 4 other CRAs but I am the only one on the West Coast. I am lucky that 7 of my sites are located near one another in LA so I can combine my visits into longer trips and not have to fly so often. I also have 2 sites in Phoenix, a site in Seattle, and a site 1.5 hrs drive East of my house. In any case, this is a heavy site load but luckily it is a straightforward study and the PIs seem to be both experienced and motivated.

An electronic patient diary looks just
like a little PDA and the patient gets
an alarm to remind them it is time
to take their medicine or fill out a
little outcomes summary. This data
gets sent in via the telephone or
loaded into a computer and is used
in the study analysis.
The trial leverages some cool technology such as an electronic data capture system (so CRFs go into the computer in an EDC system rather than on triplicate forms) and the patients all get electronic diaries (little palm pilot devices) so they can capture adverse events and be reminded when it is time to take their medicine, plus the medicine (Investigational Product - IP) comes in blister packs one week at a time, so drug accountability should be a cinch thanks to this clever packaging. This is a proof of concept study so there are 6 different study arms (some patients get placebo, some get the real drug, some get a mix of both...) and only 275 subjects will be enrolled. The subjects take their meds for around 7 weeks. Recruitment is anticipated to end in mid-April so it is a really short enrollment period. The Inclusion exclusion criteria are very tight so a high number of screen failures are expected (up to 800). Luckily, screen failures will not get their own casebooks but just be captured in the Integrated Voice Response System (IVRS) web portal.

In my next post I will tell you more about how to prepare for a CRA interview and what types of questions you can expect to be asked. Then I will post about Routine Monitoring Visits, as promised. Let me know if there are other topics that are of interest to you by emailing me or leaving me a comment here and I will be sure to address them in future posts.

Monday, January 7, 2008

Pre-Study Visits and Site Initiation Visits

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

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

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

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

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

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