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COVID-19 FDA Response:  Site Management and Monitoring

Posted by Sharon Duffy and Marina Acosta-Enslen on Mon, Apr 20, 2020 @ 10:00 AM

This blog post is the next in a series related to maintenance of the reliability and validity of ongoing clinical trial data during the COVID-19 pandemic. Previous topics included changes to study visits and assessments during COVID-19: subject safety considerations and documenting changes made during COVID-19: protocol amendments and the clinical study report. A future post is planned on data integrity: handling COVID-19 related missing data.

In this post, the focus is on site management and monitoring changes during COVID-19.

In the FDA Guidance on conduct of clinical trials of medical products during the COVID-19 pandemic, released initially on March 18th and updated on March 27th and April 2nd (with questions and answers), FDA addresses questions related to delays in on-site monitoring during the COVID-19 pandemic and recognizes access to trial sites may be limited or not available. With a focus on participant safety and trial data quality and integrity, the FDA expectation is that sponsors will identify alternative approaches to on-site monitoring and document these in updates to the Clinical Monitoring Plan. Some alternative approaches include enhanced centralized monitoring and off-site (remote) monitoring: review of subject status, data entry and query resolution, training, regulatory document review and collection, investigational product (IP) compliance, and safety reviews. More frequent off-site (remote) monitoring may need to be considered.

FDA has indicated that delays in monitoring should be carefully documented. Additionally, documentation should track protocol deviations and other GCP non-compliance issues that are a result of delayed monitoring visits due to COVID-19.

Side view of three artists working on computer at the office-1Study teams will be expected to conduct targeted risk assessments specifically focused on risks related to COVID-19 impacts on study conduct: new safety risks to trial participants; ability/willingness of trial participants to travel or travel restrictions that limit travel; continued availability of investigators, site staff and facilities; availability of trials supplies, vendors, and IP; gaps resulting from shifts in monitoring strategy due to restricted on-site monitoring. The outcome of this risk assessment should drive the mitigation response, which may include, but is not limited to: protocol amendments, holds on screening and enrollment, and updates to monitoring strategy and Clinical Monitoring Plan.

Study teams will need to determine which altered monitoring strategy best fits the current status of their studies. The study team should collect information on restrictions and the duration of those restrictions both for study participants and for on-site monitoring and confirm whether or not the site allows remote review of their electronic medical records (if applicable) or has some other secure way of reviewing site data remotely.

Study teams should ensure succession planning for themselves in the event of team member absences, limitations, or sickness related to COVID-19.

Vendor limitations or changes in service and reporting should be tracked and communicated to sites if impact is expected.


Sharon Duffy, Associate Director, Clinical Monitoring at Rho, has over 25 years of clinical research experience at both large and small CROs and sponsor companies. Starting as a CRA, she later moved into monitor training, process and compliance support. She received her B.A. in Biology from the University of Virginia.



Marina Acosta-Enslen, Associate Director, Clinical Management is a diversely skilled clinical research professional with 20 years of experience across Phase 1 through 4 studies. Prior to joining Rho, Ms. Acosta-Enslen has held positions in the areas of clinical monitoring, site level study coordination, site start-up, and clinical study management. Ms. Acosta-Enslen has extensive experience working on regional and global HIV, Oncology, Acute Pain and Vaccine clinical trials. Nearly half of her career has been focused in HIV/AIDS research working on NIH and industry funded clinical trials.

50 Must Have Travel Tips from Experienced CRAs

Posted by Brook White on Wed, Oct 25, 2017 @ 09:57 AM

Recently, I sat down with Clinical Team Leads Caitlin Hirschman and Jamie Christensen who have a combined 25 years of monitoring experience to learn more about the travel tips they’ve acquired over the years.  Here’s what they had to share:

luggage and packing


1.  Expect the unexpected.  Things will go wrong, so you just have to be patient and stay calm when you are traveling.  Going in with the expectation that everything will go according to plan is a recipe for dissatisfaction.

2.  Get loyal with an airline and hotel chain so you can reap the benefits of their rewards systems (when it isn’t cost prohibitive).  You’ll appreciate the free upgrades and other goodies that you’ll collect over time. 

3.  Have cash. It comes in handy for tips and other small items.

4.  Invest in comfortable shoes.  Wear flats and bring sneakers.

Luggage & Packing

5.  Travel with a backpack and a carry-on.  Using a backpack rather than a purse or tote bag leaves your hands free which will make things much easier.  The backpack can also serve as the go to bag while you are on-site.

6. Invest in a good carry-on.  Consider one that is small enough to fit under the seat if you’ll be going on lots of overnight trips.  That way you won’t have to gate check your bag if they run out of room in the overhead compartments or if you are on a small regional flight that doesn’t accommodate roller boards.

7. Keep a ready-to-go toiletry kit that you don’t have to repack each time that contains carry-on size liquids.

8. Aveeno makes face wipes that work well as a non-liquid facial cleanser.

9. Pack light. A good rule is to pack two shirts for each pair of pants and re-wear the pants.
10. Pack clothes that don’t require ironing.

11. Bring some candy. It can make a good pick me up when you are feeling worn down.
12. Gum can come in handy too.

13. Don’t forget your chargers.

14. De-clutter your wallet so you are only carrying what you really need.

Air Travel

15. TSA pre-check is totally worth it. Not only does it provide the convenience of not needing to take off your shoes and take things out of your bags at airport security, but the shorter lines can save you a lot of time especially at larger airports. (Rho pays for TSA pre-check for frequent travelers).

16. Delta and Southwest are favorites for airlines. If you take Southwest, it’s worth it to pay for the early bird check-in so you get a better seat assignment. The cost will be offset by what you might have spent checking your bag.air travel

17. Consider joining an airline club. It can provide a really nice break during a long layover or if you get stuck because of a flight cancellation. (Rho pays for airline club membership for frequent travelers).

18. In general, aisle seats are preferred, but window seats may be better for a redeye.

19. Make sure to get a seat close to the front of the plane if you have a close connection, even if it means taking a middle seat. A middle seat is definitely preferable to a missed connection.

20. Don’t bring fish or beef jerky to eat on the plane. Your fellow passengers will appreciate it.

21. Avoid connecting flights through New York area airports. Atlanta is a good airport for transfers.

Ground Transportation & Parking

22. Consider using Uber to get from home to the airport depending on how long you will be gone and what time your flights are departing and arriving. It can be substantially cheaper than parking and you get dropped off close to the terminal at most airports.

23. If you do need to park, consider using an off-site parking service. You can earn points, they provide amenities like coffee and newspapers, and drop you off right by the terminal and your car. It can also feel safer than walking through a parking garage late at night.

24. Consider using Uber or other ride-sharing services in cities where parking can be a problem. This may also be a good plan if your visit is at an academic site. University parking is notoriously problematic.

25. If you have a good taxi driver, get their card so you can use them for the rest of the trip or future trips to the same city. It also allows you to call ahead for a ride.


26. Download a noise machine app. It can help you sleep better in new places—particularly noisy ones.

27. Don’t sleep naked. You never know when there will be an unexpected hotel fire alarm.

28. When visiting a new site, ask them for hotel and restaurant recommendations.

29. Ask for a higher level hotel floor (never ground floor).

Health and Wellness

30. Bring an empty refillable water bottle and then fill it once you are on the other side of airport security. It’s easy to get dehydrated while you are traveling, and this is an easy, cheap, and environmentally-friendly solution.

31. Bring snacks. You never know when you are going to be stuck somewhere that it isn’t convenient to get food or where food options aren’t great. You can also choose healthier snack foods when you pack them yourself rather than purchasing them at the airport.

32. Make a plan to get in a workout wherever you go. It is easy to ignore your health when you are traveling frequently. Bring workout clothes and sneakers.eat healthy when you travvel

33. Check with your gym to find out if they have satellite locations in areas where you frequently travel.

34. Some hotels offer workout clothes and shoes that you can rent.

35. Keep your sneakers in your backpack, so you can take a walk and explore the city after work.

36. Keep hand sanitizer or baby wipes handy. Planes and airports are germy places.

37. Look under the mattress to check for bedbugs.

38. Beach Body Workouts is super cheap for a year membership. Just log onto the app and choose a workout like yoga or T25, which is a super quick great workout.


39. Make sure someone has your contact information and also knows your travel plans. Make sure to give the airline an emergency contact number. This is especially important for single folks who aren’t necessarily checking in with anyone regularly.

40. When the hotel asks you how many keys you want, always tell them two so that no one overhears that you are traveling alone.

41. Do a safety check of the hotel room before settling in. Check behind doors and in closets where someone could be hiding and make sure windows and sliding glass doors are locked.

42. If you are traveling to a new place, try to arrive when it is still light outside.

Food & Entertainment

43. Headphones for the plane are a must. You can use them to listen to music or movies, and to drown out the noise of the plane (or unruly passengers).

44. Before you leave on your next trip, download movies, books, or audiobooks to entertain yourself on the plane or when you have some free time back at your room.

45. Learn to enjoy travel by exploring each place you go. There are a number of “Best of” apps that tell you the best sandwich, beer, dessert, etc. in each state. It can be fun to see how many you can collect.

46. Some restaurant and hotel chains have happy hours which can save you some money if you are traveling on a per diem reimbursement plan. In some cases, hotel happy hours provide free food that make for a decent light dinner.

47. Bring a bathing suit. If you have free time you can get some exercise in the pool or some relaxation time beside it.

48. Go see landmarks in new cities you visit—the Seattle Space Needle, Millennium Park in Chicago, Duck Tours in Boston, Riverwalk in San Antonio.

49. Baseball games are a great way to take in some local flavor at a reasonable cost.

50. Check out some local restaurants.

What are your best travel tips?  Share in the comments below!

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Why Depression Studies So Often Fail:  Don’t Blame “Placebo Response”

Posted by Brook White on Thu, Jun 29, 2017 @ 02:34 PM

Jack Modell, Vice President and Senior Medical OfficerJack Modell, Vice President and Senior Medical Officer, is a board-certified psychiatrist with over 35 years of experience in clinical research, including 20 years conducting trials, teaching, and providing patient care in academic medicine, and 15 additional years of experience in clinical drug development (proof of concept through market support), medical affairs, successful NDA filings, medical governance, drug safety, compliance, and management within the pharmaceutical and CRO industries. Jack has authored over 50 peer-reviewed publications across numerous medical specialties and has lead several successful development programs in the neurosciences. Jack is a key opinion leader in the neurosciences and is nationally known for leading the first successful development of preventative pharmacotherapy for the depressive episodes of seasonal affective disorder.

Prior to joining the pharmaceutical and contract research organization industries, I was in clinical practice for twenty years as a psychiatrist and medical researcher.  And something I noticed very early on among my patients with major mental illnesses, particularly those with severe depression and psychotic disorders, was that they did not generally get better – at least not for more than a day or two – by my simply being nice to them, treating them with ineffective medications (e.g., vitamins when no vitamin deficiency existed), seeing them weekly for office visits, or by providing other so-called supportive interventions that did not directly address the underlying illness.  To be clear, this is not to say that kindness and supportive therapy are not critical to the patient-physician relationship (“The secret of the care of the patient is in caring for the patient” [Frances Weld Peabody, 1927]), but rather that kindness and support alone rarely make a biologically based illness substantially improve or disappear. 

With this background, I vividly recall my surprise upon being asked shortly after I joined the pharmaceutical industry:  “Can you help us figure out how to decrease the nearly 50% placebo-response rate we see in antidepressant trials for major depressive disorder?”  “Fifty percent?” I replied, incredulously.  “There’s no way that 50% of patients in a true major depressive episode get better on placebos or just by seeing the doctor every couple of weeks!”  “Seriously?” was the reply, and they showed me voluminous data supporting their figure.

I spent the next few years trying to figure out this apparent paradox.  Not surprisingly, the answer turned out to be multifactorial.  After careful review of internal and external data, as well as published explanations for high “placebo response rates” in clinical depression trials (much of which also applies to clinical trials in general), the following three factors emerged as being of particular importance because they are easily mitigated by proper trial design, thorough research staff training, and meticulous oversight of study conduct.

(1)  Subjects being admitted into clinical trials often had depressive symptoms, but did not truly meet criteria for major depressive disorder.  Examples include subjects with personality disorders whose symptoms wax and wane considerably with external factors (e.g., family or job stress), subjects with depressive symptoms in response to a particular stressor (not of sufficient severity or duration to meet formal criteria for a major depressive episode and likely to abate with the passage of time), and subjects who – for various reasons – may feign or exaggerate symptoms for the purpose of seeking attention or gaining access to a clinical trial.  Unlike the patients I encountered in my clinical practice, subjects with these presentations often do improve with supportive interventions and placebo. 

Recruitment of truly depressed subjects is made even more difficult by the widespread availability of reasonably effective medication options. Patients in the throes of a major depressive disorder, who sometimes have difficulty even making it through the day, are rarely keen to commit to the additional efforts, uncertainties, and treatment delays involved with a clinical trial when an inexpensive prescription for an effective generic antidepressant can now be filled in a matter of minutes. Indeed, as more and more generally safe and effective medications have become approved and readily available for a variety of illnesses, the motivation for patients to join clinical trials in the hope of finding an effective treatment has correspondingly decreased.

(2) The second factor is somewhat difficult to discuss because it sometimes provokes an understandable defensive response in clinical investigators.  Consciously or unconsciously, many investigators and clinical raters inflate or deflate clinical ratings to enable the subject to gain entry into, or remain enrolled in, a clinical trial.  Most commonly, this is done by subtly – and sometimes not so subtly – coaching subjects on their answers, or when subject responses or findings seem to fall in between scale severity ratings, by rounding up or down to a rating that is more likely to qualify the subject for the trial. 

The effect of this practice is diagrammed in the following figures, specific examples of which can be seen in these references.1-3 In Figure 1, the white bell-shaped distribution is the expected distribution in severity rating scores of an unselected clinical population presenting for clinical trial participation, let’s say with a mean score at shown at X̄n. Not uncommonly, what we see in clinical trials in which a certain scale severity score is required for study entry (depicted by the vertical light blue line, with a score to the right of it required for entry) is not the expected right half of this bell-shaped distribution, but rather a distribution like that shown by the orange curve, which is essentially the right-half of the bell-shaped distribution with a large proportion of subjects whose ratings fell short of required severity for study entry (to the left of the blue line) “pushed” to the right, over the blue line, so that the subjects now qualify for study inclusion, with the mean of those thus selected shown at X̄s.

Figure 1


At the first follow-up visit, when raters (and subjects) now have little incentive to influence rating scores to meet a pre-specified criterion, the scores of the entire included population are free to relax towards their true values and assume the pre-selection and more normally distributed pattern.  Moreover, subjects and investigators, expecting that the onset of treatment should coincide with at least some clinical improvement, may bias rating scores during this period to reflect this expectation even though the signs and symptoms of the illness may have yet to show true change.  During this same time, any actual clinical improvement will also result in the rating score mean shifting leftward (white arrow, figure 2), but because the measured change – from the initial X̄s of the selected population to the new mean (X̄n1; orange arrow, figure 2) – is generally much greater than a true treatment effect during this period, any real changes are obscured and the ability to detect a true drug-placebo difference may be lost.  While this early “improvement” in rating scores for subjects in clinical trials may appear to be a “placebo effect” and is often confused with it, this apparent improvement is instead the result of artificially inflated scale scores regressing back to their original true distribution, in combination with whatever actual treatment and placebo effects may have occurred during this time.  Unfortunately, the introduction of non-qualified subjects to the study and rater bias will continue to hamper detection of actual drug-placebo differences throughout the course of the study.

Figure 2


(3) Finally, investigators and site staff often do not fully understand the true objective of the clinical trial:  it should never, for example, be “to show treatment efficacy” or to show that a product is “safe and well tolerated,” but rather, to test the null hypothesis of no treatment difference or to estimate likely treatment effect, as well as to faithfully and objectively record all adverse effects that may emerge during treatment.  Likewise, investigators and site staff often fail to understand the importance of complete objectivity and consistency in performing clinical ratings, the intention behind and importance of every inclusion and exclusion criterion (necessary for their proper interpretation and application), and the destructive effect on the outcome and scientific integrity of the trial that even well-intended efforts to include subjects who are not fully qualified can have.  

Each of these three factors can skew both drug and placebo trial populations and results, making it appear that subjects “improved” well beyond what would have resulted had there been strict adherence to protocol requirements and objective assessment of study entry and outcome measures.

What, then, can be done to prevent these problems from sabotaging the results of a clinical trial?  Foremost are thorough and meticulous investigator and rater education and training.  All too often, perfunctory explanations of the protocol and clinical assessment tools are provided at investigator meetings, and “rater training” takes the form of brief demonstrations of how the rating scales are used and scored, without actually testing raters to be certain that they fully understand how the scales are to be used and interpreted, including understanding scoring conventions, criteria, and necessary decision-making.4  Even seemingly sound training has marked limitations both immediately and as training effects deteriorate during conduct of the trial.4-7 

Training of the research staff must include not only a review of the protocol design and study requirements, but detailed explanations about why the trial is designed exactly as it is, the importance of strict adherence to study inclusion and exclusion criteria, and the necessity for complete honesty, objectivity, and consistency in conducting the clinical trial and in performing clinical assessments.  Detailed training on the disease under study is also important to ensure that all site staff have a complete understanding of the intended clinical population and disease being studied so that they can assess subjects accordingly.  And, as noted above, rater training must include not only education on the background, purpose, characteristics, and instructions for each scale or outcome measure used, but trainers, as well as investigators and raters, should be tested for adequate understanding and proficiency in use of each of these measures. 

Meticulous monitoring during the course of the study is also essential to ensure continued understanding of, and compliance with, protocol requirements, as well as accurate and complete documentation of study procedures and outcomes.  Study monitors and others involved with trial oversight should review data during the course of the trial for unexpected trends in both safety and efficacy data, and not simply for identification of missing data or isolated datum outliers.  Unexpected trends in safety data include adverse event reporting rates at particular sites that are much higher or lower than median reporting rates, and vital signs that are relatively invariant or favor certain values over time.  Unexpected trends in efficacy data include changes in closely related outcome measures that are incongruent – for example, objective and subjective ratings of a similar outcome differing considerably in magnitude or direction, that are much larger or smaller at particular sites than those observed at most sites, that occur in relatively fixed increments, and that show unusually similar patterns or values across subjects. 

Finally, and perhaps most importantly, is that no matter how well-informed or well-intentioned investigators and raters might be, humans simply cannot match computers in objectivity and consistency, including of the kind needed to make assessments based on subject responses to questions in clinical trials.  Unless being programmed to do so, a computer cannot, for example, coach a subject on how to respond, nor would it inflate or deflate ratings based on feelings, expectations, response interpretations, or desired outcomes.  A computer faithfully asks the same questions every time, following the same algorithm, and records responses exactly as provided by the subject.  Indeed, several studies have shown that computerized assessments of entry criteria and outcome measures in clinical trials – in particular interactive voice response systems (IVRS) and interactive web response systems (IWRS) – provide data of quality and signal-detection ability that meet and often exceed that obtained by human raters.1,3,7,8,9  For these reasons, strong consideration should also be given to using IVR and/or IWR systems for assessing study entry criteria and endpoints that allow such use.  

The author acknowledges John H. Greist, MD, for his outstanding research and input regarding these important findings and considerations.


  1. Greist JH, Mundt JC, Kobak K.  Factors contributing to failed trials of new agents:  can technology prevent some problems.  J Clin Psychiatry 2002;63[suppl 2]:8-13.
  2. Feltner DE, Kobak KA, Crockatt J, Haber H, Kavoussi R, Pande A, Greist JH.  Interactive Voice Response (IVR) for Patient Screening of Anxiety in a Clinical Drug Trial.  NIMH New Clinical Drug Evaluation Unit, 41st Annual Meeting, 2001, Phoenix, AZ.
  3. Mundt JC, Greist JH, Jefferson JW, Katzelnick DJ, DeBrota DJ, Chappell PB, Modell JG.  Is it easier to find what you are looking for if you think you know what it looks like?  J Clinical Psychopharmacol 2007;27:121-125.
  4. Kobak KA, Brown B, Sharp I, Levy-Mack H, Wells K, Okum F, Williams JBW.  Sources of unreliability in depression ratings.  J Clin Psychopharmacol 2009;29:82-85.
  5. Kobak KA, Lipsitz J, Billiams JBW, et. al.  Are the effects of rater training sustainable?  Results from a multicenter clinical trial.  J Clin Psychopharmacol 2007;27:534-535.
  6. Kobak KA, Kane JM, Thase ME, Nierenberg AA.  Why do clinical trials fail.  The problem of measurement error in clinical trials:  time to test new paradigms?  J Clin Psychopharmacol 2007;27:1-5.
  7. Greist J, Mundt J, Jefferson J, Katzelnick D.  Comments on “Why Do Clinical Trials Fail?”  The problem of measurement error in clinical trials:  time to test new paradigms?  J Clin Psychopharmacol 2007;27:535-536.
  8. Moore HK, Mundt JC, Modell JG, Rodrigues HE, DeBrota DJ, Jefferson JJ, Greist JH.  An Examination of 26,168 Hamilton Depression Rating Scale Scores Administered via Interactive Voice Response (IVR) Across 17 Randomized Clinical Trials.  J Clin Psychopharmacol 2006;26:321-324.
  9. http://www.healthtechsys.com/publications/ivrpubs2.html 

Webinar: Selecting Inclusion/Exclusion Criteria for Your Next Trial

Key Take-aways from ACRP 2017

Posted by Brook White on Fri, May 05, 2017 @ 11:15 AM

key take aways from ACRPThis week I attended the 2017 ACRP Annual Meeting in Seattle.  Here are some of the key trends, themes, and ideas that I took away.  There were obviously far more sessions than any one person could attend, so I’m sure there are pieces I missed.  If you attended, please feel free to add your thoughts to the comments below.

Core Competency Framework for Clinical Study Monitoring

framework for clinical study monitoringOne of the biggest announcements of the conference was that the Workforce Development Task Force and Steering Committee released a core competency framework for clinical study monitoring.  The goal of the framework is to standardize professional expectations for individuals involved in clinical study monitoring.  The framework is intended to define competency requirements for individuals involved in study monitoring regardless of experience level across eight domains—clinical operations/GCPs, communication and teamwork, data management and informatics, ethical and participant safety concerns, leadership and professionalism, medicines development and regulation, scientific concepts and research design, and study and site management. The core competency framework can be downloaded here.

ACRP Announces New Certification Program

certified professionalACRP announced a new certification program, ACRP-CP (certified professional).  The new certification provides a non-role specific alternative to the existing role specific Certified Clinical Research Associate (CCRA), Certified Clinical Research Coordinator (CCRC), and Certified Principal Investigator (CPI) certifications.  The new credential seeks to formally recognize individuals with the skills, knowledge, and abilities to perform ethical and responsible clinical research regardless of their specific role.  The first certification exam will be held this Fall.

Transparency and Flexibility from FDA

regulatory transparencyThe first session on Saturday was a panel discussion with four speakers from FDA—three from the Center of Drug Evaluation and Research (CDER) Office of Scientific Investigations (OSI), and one from CDER Office of Integrity and Surveillance. As I commented following ACRP and DIA last year, FDA seems to be making a concerted effort to be accessible, transparent, and flexible in communicating with professionals involved in research. As a matter of fact, one of their stated strategic goals was stakeholder engagement (the others were user fee requirements, responsible stewardship, global context, and subject rights, safety, and welfare). They also stated that in places where existing guidance and precedence doesn’t exist and is needed to move research forward, drug developers should come to them with questions rather than waiting for formal guidance. In addition to the panel discussion, the three speakers who attended in person stuck around and held office hours Saturday and Sunday to talk to conference participants.

The panel addressed several questions that related to themes seen more broadly at the conference.

State of the Industry

Day 2 opened with a panel discussion on the state of the industry featuring ACRP President Jim Kremidas, Ken Getz from Tufts University Center for the Study of Drug Development (CSDD), Elisa Cascade, President of Data Solutions, Leanne Madre Director of Strategy for the Clinical Trials Transformation Initiative (CTTI) at Duke University, and ACRP’s Workforce Innovation Officer, Terri Hinkley.  The panel focused their discussion on four broad forces impacting clinical trials:

  • Consolidation
  • Datafication
  • Integration
  • Uberization

Organizations involved in clinical trials are consolidating across the continuum. We are seeing both consolidation for economies of scale—CRO mergers and acquisitions, sites fusing into site networks—and vertical consolidation where organizations are increasing their capabilities—CROs buying site networks and central labs. It remains to be seen how this will impact clinical trials as a whole.

Datafication is the increased ability to gather and access ever increasing amounts of both structured and unstructured data that can be used in clinical research. The average phase III study now collected nearly 1 million data points. Additionally, we are seeing more data that is collected to drive payer and prescriber behavior rather than just to demonstrate safety and efficacy.

Integration refers to the efforts to better connect people, processes and technology. There are a number of national level initiatives to improve clinical research like CTTI, TransCelerate, and MDIC, a device and diagnostic initiative. These organizations have potential to move some agreed upon concepts from idea to reality. For example, both the NIH and the 21st Century Cures Act call for use of central IRBs, and CTTI is working on tools that can help make that happen. When it comes to technology, the perception is that the industry is suffering from “death by pilot.” People and organizations are willing to try lots of new technology, but consistent industry wide adoption is incredibly slow and lacking in standardization. Even EDC, which is hardly new or innovative at this point, is only used by 50% of studies globally. Common complaints and barriers include lack of consolidated platforms and the need to use different software and different login information for each study.

Uberization is moving research into healthcare in a way that works best for patients. There are greater pressures than ever to make research patient friendly rather than convenient for sites, PIs, CROs, and sponsors. Without patients, studies won’t happen. In this talk as well as others, there is a sense that patient centric practices aren’t just the right thing to do, they are necessary to succeed in research.

Finally, the panel identified key drivers for change over the next 3-5 years:

  • Collaboration: Industry and CROs working together allow for standardization and process improvement.
  • Regulatory willingness to try new things.
  • The internet of things—devices in our lives provide access to information in new and objective ways.
  • Technology that is easy enough to use that training isn’t necessary.

Innovating Clinical Trials with Mobile Technology

mobile technology for clinical trialsDay 3 featured a panel discussion on the CTTI mobile technology initiative.  The initiative contains four working groups addressing:

  • Mobile devices
  • Novel endpoints
  • Stakeholder perceptions
  • Legal and regulatory issues

The goal is to provide evidence-based recommendations that allow an increased number of clinical trials to leverage mobile technologies.

One question they addressed upfront was the benefit of using mobile given the additional effort needed, and they provided four key answers:

  • Potential reduction of burden on trial participants
  • Increased patient access to clinical trials
  • Availability of objective data
  • Ubiquity of devices

The initiative has focused on studies conducted in the US, although they recognize it is a global issue. The stakeholder perception group is addressing concerns about security as well as concerns about losing the time and attention of the doctor providing care. The novel endpoints group is looking at new endpoints that are now possible to assess as well as existing endpoints that can be assessed more easily or more accurately than is possible with non-mobile technologies. The mobile devices group is looking at devices that can address existing challenges, data attribution concerns, and the identification of the difference between real needs to address research questions versus data fishing expeditions. The legal and regulatory group has its hands full with a variety of issues—understanding FDA’s willingness to accept mobile technologies, addressing privacy and confidentiality concerns, telemedicine challenges, dealing with IRBs, shipping issues, and reimbursement.

Finally, people were invited to engage in the process by signing up for updates or to participating in evidence gathering (ctti@mc.duke.edu).

eHRs and Study Oversight

A significant concern expressed by auditors and monitors alike in a number of sessions is that site and institutions implementation of eHR systems do not provide adequate mechanisms for monitors and auditors to provide oversight.  In some cases they are being provided with copies or printouts that are illegible rather than provided with direct access to eHR systems.  In other cases, they are provided with access to eHR systems, but important information is sequestered.  A common complaint is that sensitive records like those associated with mental illness, sexually transmitted infections, and substance abuse is are not being made available even when those records are relevant to the research and may reflect AEs.  In one example, it came to light that a subject had attempted suicide while on an investigational product, but it was not initially reported as an AE and the study monitor was not allowed access to the record.  With the increased use of eHRs in healthcare settings, this is not likely an issue to go away soon.


Not surprisingly, many if not most sessions touched on the impact of the ICH E6 revisions and their impact to studies.  Additionally, there was a two part session held specifically to review the revisions and discuss their impact.  This is an extensive topic that is well discussed elsewhere, so I won’t go into detail here. 

Importance of Conducting Ethical Research

While this isn’t new, ACRP continues to press the importance of conducting clinical research in ethical ways and expecting professionals involved in research to understand what that means.  There were a number of excellent sessions on research misconduct and the relationship to public trust, ethical considerations in pediatric research, and recognizing vulnerable patients and patient populations.

Business Intelligence and Study Management

As the global volume of available data sources increases exponentially, those in clinical research are becoming more aware of the benefits of transforming these raw data sources into useful information for analysis purposes. The ability to effectively utilize the data we currently have depends on the thoughtful construction of metrics and key performance indicators (KPIs). The simple establishment of these types of measures must develop an even balance; a study can have too many metrics (which confuse the purpose), too few metrics (which offer weak benefit and minimal impact), or a focus that is too broad where one area grows strong at the expense of another. Other common pitfalls are underestimations of the time and effort required to combine various data sources, imbalances between metrics and action, and metrics that are developed for the sake of metrics. The development and use of these metrics and KPIs requires a cycle of continuous improvement: High-impact metrics must be identified and developed, accurate data gathered, and the lessons learned converted to actionable strategies and reassessed continually to correctly estimate our return on investment.

Thanks to Derek Lawrence for contributing to this article.

Not Just Tiny Humans: Considerations for Conducting Pediatric Clinical Trials

Posted by Brook White on Tue, Apr 25, 2017 @ 09:43 AM

Jamie Arnott, BSN, RN--Project DirectorCaitlin Hirschman, RN, BSN--Clinical Team LeadProject Director Jamie Arnott, RN, BSN and Clinical Team Lead Caitlin Hirschman, RN, BSN have extensive experience in pediatric clinical research including recent studies in rare diseases and diseases with a seasonal component.

When it comes to the conduct of pediatric clinical trials, there are number of things you need to consider in order to ensure the successful conduct of a study. While we can’t predict the outcome, planning ahead for appropriate site conducting clinical studies in pediatric patient populationsand subject selection will take you one step closer. From study design to logistics to recruitment, there are real differences between studies conducted in pediatric populations and studies conducted in adult populations.

Patient Recruitment

While patient recruitment can be challenging in any study, there are additional challenges to recruiting pediatric patients.  Parents may be more risk averse to giving an unproven therapy to their child than they would towards receiving it themselves.  To improve the chances of successfully enrolling a study, it is important to consider potential motivators for participation:

  • Therapeutic benefit: If you are working on a therapy for a rare disease or for an indication where there is no approved or effective product, parents may be motivated by the opportunity to receive treatment that could improve their child’s condition even if it isn’t proven and if there is a chance they will receive placebo.  When there is an approved effective treatment available parents are likely to be reluctant to sign their child up when they may receive placebo, receive a treatment whose effectiveness is unknown, or receive a treatment with unknown side effects and safety issues.
  • Financial incentives: Many studies offer financial incentives to participants, and this can be a motivating factor for some parents.  Additionally, patients may receive study related medications, assessments, or more routine care that could be cost prohibitive otherwise.
  • Research benefit: Particularly for studies in rare disease or orphan indications, parents may see the benefit in research that provides a better understanding of the disease or the prospect of better treatment options in the future even if their child does not receive a direct benefit in participation.

Understanding what motivates parents to allow their child to participate in a clinical research study will help you to determine how to advertise and recruit for your study.  Some recruitment tactics (with appropriate ethics committee approval) to consider include:

  • Directly reaching out to parents by calling or through email.
  • Advertising at family events or locations where children and parents are likely to attend.
  • Reaching out to healthcare providers who may be the patients’ first point of contact even if they are not the location where the study will be conducted.  For example, if you conduct a study where the sites and investigators are typically at specialty practices, you may still want to recruit through primary care providers.
  • Consider referral processes for these types of sites to ensure patients are considered in a timely manner, based on their indication/treatment needs.

Patient Retention

using electronic devices in pediatric clinical studiesGetting pediatric patients enrolled in a study is great, but it is just as important to make sure most patients are completing the study.  There are a number of factors that make this more difficult in a pediatric study:

  • Multiple schedules to coordinate: Each study visit requires both the parent and child to be available.  Studies with numerous visits can become a significant hassle for parents, which can lead to discontinuations.  Making sure that every visit is necessary and being as accommodating as possible with scheduling, such as including flexible visit windows can mitigate this risk. (Remember: Most of the parents still have to work and kids attend school).
  • Parents don’t see the therapeutic benefit: If parents come to believe that their child is receiving placebo or that the treatment is ineffective, they may withdraw their child from the study. Providing clear information about what the trial is evaluating and encouraging frequent communication will help facilitate the parent voicing any concerns.
  • Discomfort of participation: No one likes long doctor visits or being stuck repeatedly with a needle, but these discomforts are even harder on pediatric patients and their parents.  Evaluate each assessment carefully during protocol development (even ones like blood pressure and temperature monitoring) to reduce the overall burden to the patient.

What can be done to improve retention? Encourage investigators to talk with parents about the importance of completing the study.  Consider what incentives may be appropriate to improve retention and work within the limitations of what the IRB will allow based on your study. Cash incentives may be effective with older patients and with parents.  In some cases, we’ve seen where study information or assessments are loaded on a device like a tablet that the patient may get to keep at the end of the study.  Treats or fun activities such as coloring books or video games to play at study visits can be good incentives for younger patients.  Keep in mind that there may be limitations on what you can provide as incentives.  All incentives will require IRB approval. Finally, keep visits as short as possible, limit blood draws and invasive procedures, that every procedure and assessment is truly necessary to determine the safety or efficacy of the investigational product.

Informed Consent

Pediatric studies introduce several challenges when it comes to informed consent:

  • Typically, if patients are at least 7 years old, in addition to parental consent you will need assent from the patient.  Assent documents will need to be written at an appropriate reading level.
  • In pediatric studies, parents are likely to want to know which treatment their child received and the outcome of the study after the study is complete.  Information on whether this will be made available needs to be included in the consent document.
  • You will need to decide whether consent is required from both parents.  If not, and the parents are divorced, can either parent make the decision?  If you do need consent from both parents, this can be an additional hurdle to enrollment.

Other Considerations

In our experience there are a number of other considerations that require proper planning to ensure study success:

  • Pregnancy tests: In many cases, pregnancy tests will be needed for female patients.  Depending on the age of the child and the view of the parents, this may be a hurdle.  In many cases, these tests are required at an earlier age than parents anticipate—typically as young as 9 years old.  Parents and patients do need to be informed if the test is being done.
  • Objective outcomes: For studies with young patients, objective outcomes are highly preferable to outcomes that rely on the reporting of the patient or parent.  If patient-reported scales are used, staff will need to be trained to get answers from the patient rather than the parent.
  • Sibling bias: The protocol will need to specify whether siblings can participate in the study.  Allowing siblings to participate may be helpful for enrollment, but it can also introduce bias into the results and potentially create a risk if home treatment is required.  There is a risk that if siblings are in different treatment arms, the treatments could be mixed up, while at home,  resulting in subjects receiving the incorrect treatment.
  • Dosing during school hours: If the protocol requires dosing during school hours, this may require extra paperwork/legwork on the part of the parent to gather supportive information allowing the school staff to give this investigational product (IP).  Many schools will not give IP to students and may not allow students to retain IP even if it is self-administered.
  • Missed school: Frequent visits during the school day or overnight visits may cause absenteeism issues for school-aged children.
  • Continuation: Consider whether participants will be able to continue receiving the product after the study, for example, through an open label extension of the study.  Even for a Phase III study, it may be several years before a product receives marketing approval.

Conducting clinical research in pediatric populations does introduce a unique set of challenges.  With proper planning, however, many of these challenges can be avoided or mitigated.

Download 5 Lessons Learned Conducting ADHD Trials

Six Things to Consider When Selecting a CRO for your next Pain Trial

Posted by Brook White on Thu, Mar 09, 2017 @ 01:35 PM

Emily Cantrell, Senior Director OperationsEmily Cantrell, Senior Director Operations, has ten years of experience managing Phase 1-3 trials and utilizes her experience and customer service background to ensure seamless communication throughout the life of a trial. Her focus has been in pain management, including successful management of six full-service Phase 2 and 3 pain trials from study start through NDA submission. 

Ben Vaughn, Principal Statistical ScientistBen Vaughn,Principal Statistical Scientist, has participated in over 25 marketing applications and is an expert on CDISC implementation and standards. His work has included coproducing the ISS/ISE for multiple analgesic products; and statistical consultation, display generation and submission work for several chronic and acute pain products. In the past three years, he has supported five opioid sponsors at DAAAP advisory committee meetings, both back room and bullpen.

Pain trials are unique among clinical trials, and it is important to select a clinical research partner that understands and embraces the many differences. There are several key factors to consider when choosing a CRO to work with on your next pain trial.

1. Enrollment

In any pain study, enrollment may present a challenge. For example, in acute pain model studies, sites tend to enroll quickly and sponsors can find themselves in an over-enrollment situation. Some overage can be helpful to account for subjects withdrawing early from the study, but too much overage can significantly impact exceed the trial’s budget. Sponsors must work with the CRO to set a reasonable cap on the overall number of subjects enrolled to minimize overages while allowing sites to continue to enroll without undue restrictions. For example, for a phase III bunionectomy study, we were able to complete enrollment seven weeks early while managing the enrollment cap by using experienced CRAs and maintaining strong relationships with high performing sites.

Chronic pain studies present the opposite challenge. Enrollment is usually much slopain clinical trial enrollmentwer than what sponsors hope for, as chronic pain studies can be a tough sell for subjects. Why enter a trial if your current medication is already working and risk receiving a placebo, a rescue medication offering little analgesic control, or an experimental new drug which may or may not work? Naturally, this presents challenges when meeting predetermined time
lines. During a recent osteoarthritis study, we were able to complete enrollment early by expanding advertising programs across all sites, closing underperforming sites while increasing enrollment caps at high enrolling sites, and continuing to run advertisements throughout the entire enrollment period.

In both situations, transparency with your CRO is key. Understanding a realistic budget and timeline will help keep your trial running smoothly. Your CRO should be able to provide data to support budget and timeline projections. At times, sponsors may be reluctant to approve advertising expenses upfront. For one particular sponsor, we were able to provide them with a comparison of the advertising costs versus the cost of extending the timeline if enrollment targets weren’t met. This comparison encouraged them to move forward with early advertising, and, as a result, their enrollment target was met.

During site identification for another study, it became apparent to us that some of the sites provided by the sponsor were likely to enroll few, if any, patients. We recommended dropping these sites in favor of higher enrolling sites or adding a couple of additional sites to make sure that enrollment rates met their expectations. The sponsor declined because the investigators at those sites were key opinion leaders (KOLs) and they didn’t want the additional expense of adding more sites. In the end, it took an additional 2 months to complete enrollment. Sometimes it is a choice between paying more upfront to reduce the risks of slow and costly enrollment period extensions.

Another obstacle we see is that some sponsors estimate site budgets too low rather than market value for site payments. While we do our best to negotiate the best site agreements we can on behalf of sponsors, unreasonable budget expectations can lead to a study not being able to initiate enough (or the right) sites. The costs in timeline extensions often exceed the costs of offering market-based site payments upfront. Your CRO should be able to provide you with market-based estimates for site payments based on your study design and their experience in similar studies.

2. Subject Reported Data

Pain is not usually a visible condition. A health care professional cannot look at a subject and objectively determine how much pain that person is in. The only way to gather data during pain trials is to ask the subjects to report the information themselves. Any time subjects must provide their own data from a trial, site staff must be educated to work with subjects to better standardize subjective data collection. Similarly, subjects must receive training from site staff on how to report the information, whether electronically or on paper.

If an abnormal value entered by the subject is discovered in your data, the site cannot go back and request a clarification. For example, a subject reporting only to one extreme – all 10s say, or all 1s – is not considered clean data. In an acute pain trial, it would need to be determined how to best represent these outlier data. In a chronic trial, the study team and CRAs must revisit the site for retraining purposes.

3. Data Monitoring

clinical trial data monitoringBecause there is generally a great volume of data collected in any pain trial, it is important that a CRO monitor these data regularly. This requires a keen eye and can be quite time consuming, particularly in acute pain trials because subjects may leave the clinic before data is available to the study team. However, frequent visits to a site can help catch errors and irregularities before they become a major concern. The study team should look for outliers in the data to identify sites that may need more frequent monitoring visits or additional training for site staff. It is also important to have an experienced CRA capable of monitoring the large amount of data while visiting sites.

To manage this, many sponsors require that CRAs for pain trials have a certain level of experience. As a result, sponsors should be mindful to ensure their selected CRO can meet these expectations for staffing purposes.

4. Drug Preparation

For many pain trials, the investigational product (IP) or rescue medication may be a controlled substance scheduled by the DEA. CROs must be familiar with both DEA and state licensing requirements and forms and must also have an understanding of how to ship, move, and monitor scheduled drugs.

5. Diversion & Misuse

drug diversion and misuseDiversion and misuse of medications can be an issue in pain trials, particularly for chronic subjects. If IP counts appear incorrect, sponsors need to determine if it was a mistake or something more. The CRAs should work closely with sites to ensure IP accountability is performed on a very regular basis.

Because pain, is not necessarily a visible condition, site staff need to be diligent in recognizing suspicious behavior and detecting drug-seeking individuals. This is another area where a well-trained site can make all the difference. It is imperative to consider these points during the site selection process.

6. FDA Approval

FDA approvalA final point to consider when selecting your CRO is the experience of the team in supporting submissions for Food and Drug Administration (FDA) approval. DEA-scheduled drug trials not only need to demonstrate safety and efficacy, but must also address the human abuse liability/potential (HAL/HAP). Additionally, FDA’s Division of Anesthesia, Analgesia and Addiction Products (DAAAP) has been quick to enforce the recommendations of a 2010 FDA position paper on missing data, so sponsors must be extremely precise in their treatment of missing data or risk rejection.

Ultimately, there are many considerations a sponsor must make when selecting a CRO for a pain trial. Trained and experienced project staff are key in keeping trials moving forward with ease, detecting potential issues and monitoring vast quantities of data quickly. Any CRO seeking work on pain trials should also be prepared to demonstrate positive relationships with study sites, which can help ensure good subject recruitment and produce clean data.

Free Ebook: Analgesia Protocols

Tips for Effective Enrollment Tracking

Posted by Brook White on Thu, Jan 05, 2017 @ 10:05 AM

Heather Kopetskie, Senior BiostatisticianHeather Kopetskie, MS, is a Senior Biostatistician at Rho. She has over 10 years of experience in statistical planning, analysis, and reporting for Phase 1, 2 and 3 clinical trials and observational studies. Her research experience includes over 8 years focusing on solid organ and cell transplantation through work on the Immune Tolerance Network (ITN) and Clinical Trials in Organ Transplantation (CTOT) project.  In addition, Heather serves as Rho’s biostatistics operational service leader, an internal expert sharing biostatistical industry trends, best practices, processes and training.

It’s important to track enrollment of a trial over time to make sure accrual goals are met but knowing the enrollment number alone isn’t sufficient to know how a study is progressing. Viewing enrollment visually can provide a quick overview of how enrollment is progressing in the trial as a whole but also how specific sites are performing, whether enrollment goals will be met, and key information about the enrollment population. Below are some graphics that have been valuable for us to keep track of site performance.

Most trials start with a rolling site activation as many factors impact when a site may be activated. Along with this each site may have a different target enrollment for a trial. The below Enrollment Over Time graph takes into account when sites are activated and their target randomization rate to show target rates over time to meet accrual goals along with actual enrollment rates. In addition to overall study status, the graph can be subset to review a particular sites status. In the Overall Enrollment bar graph, a quick overview of how many subjects have been screened, enrolled, and randomized at each site along with the target accrual are shown to quickly see which sites are performing and which sites need additional follow-up.

enrollment metrics

In some studies, it’s important to track sub-groups of enrollment. This can be done by including sub-bars that show what percent of subjects are in each group.



Dropout is a concern in many trials when the sample size guidelines project what is expected and how certain dropout rates will affect the power of the primary analysis. This graph lets us keep track of how we are doing with staying within the pre-specified dropout rates to ensure we aren’t loosing too much power to evaluate the primary endpoint.

study dropout tracking

Tracking enrollment overall and by site can help the study team manage the study and focus their efforts on sites that are lagging behind. Close monitoring of study dropouts is valuable so additional retention strategies can be put in place if needed before the number of dropouts has a detrimental effect on the power of a trial. 

Download: 5 Tips for Conducting Feasibility for a New Clinical Trial

Statisticians and Critical Variable Review Help Streamline Data Management and Clinical Operations Activities

Posted by Brook White on Mon, Oct 24, 2016 @ 10:11 AM

Heather Kopetskie, Senior BiostatisticianHeather Kopetskie, MS, is a Senior Biostatistician at Rho. She has over 10 years of experience in statistical planning, analysis, and reporting for Phase 1, 2 and 3 clinical trials and observational studies. Her research experience includes over 8 years focusing on solid organ and cell transplantation through work on the Immune Tolerance Network (ITN) and Clinical Trials in Organ Transplantation (CTOT) project.  In addition, Heather serves as Rho’s biostatistics operational service leader, an internal expert sharing biostatistical industry trends, best practices, processes and training.

risk.jpgAssessing risk and using it to determine the focus of clinical trial activities has been an important goal in clinical research for a number of years now. One way statisticians can contribute to this is through critical variable review. In critical variable review, statisticians map the case report form (CRF) to the primary and secondary endpoints.

This review is important for several reasons and impacts all team members managing the clinical data. First, it ensures upfront that all of the data needed for the planned analyses are being collected. While this seems obvious, in an unfortunate number of cases, it is not until the end of the study that teams discover that all of the information needed has not been collected. Second, data managers can incorporate critical variables into the data management plan to focus edit checks, cross checks, and data cleaning activities on forms containing critical variables. Third, clinical monitors can focus the clinical monitoring plan on critical variables and ensuring key variables are reviewed during on-site visits but also during remote data monitoring.

Statisticians, data managers, and clinical monitors should start reviewing data as early as possible after first patient first visit with a focus on critical variables. Initially focusing on a report showing for each critical variable how many subjects are expected to have the data, how many have completed data entry, and how many are missing the variable. These reports can be used to identify issues early in a trial and determine how to address issues such site retraining that’s required, process changes when an assessment isn’t standard of care at a site, protocol deviations resulting from missing data, etc. As the study progresses descriptive statistics can be performed on the critical variables for investigators to review and ensure the study is progressing as expected without unblinding the study.

data-review.jpgAs data management evolves from data primarily being collected in an EDC system to data being collected from multiple sources such as EDC, ePRO systems, health electronic records, and central laboratories, additional strategies need to be implemented to ensure a clean integrated database for analysis. Instead of data managers providing all the data cleaning data managers, programmers, statisticians, and clinical monitors will need to collaborate. All members of the team should meet regularly to discuss progress and develop tools that will facilitate cleaning across multiple data sources. New tools and strategies will need to be implemented. We outline a few strategies we’ve piloted for collaboratively reviewing data early after database launch. Early looks at the data can provide a sense of how sites are entering data. Dealing early on with issues that arise will prevent lots of dirty data at the end of the study.

One strategy is an evaluation of all free text fields completed in the database. Sites may be entering data in the wrong place or collecting data that is not needed which can be fixed through site re-training. Additionally, this review can highlight additional fields or updates that need to be added to the CRFs.

Another strategy is code book reviews. A code book is a file which provides descriptive statistics on all fields in the EDC system that can be reviewed by all members of the study team. This is an easy way to identify outliers by data field and site-to-site differences. (Codebook examples and macros are available in Github.)

Statisticians and programmers can also compile data across multiple sources to identify what data fields are missing (ePRO not entered), what information doesn’t reconcile (e.g. biopsy date in EDC versus specimen collection system), what deviations may be expected from data sources outside of EDC, etc. and provide one succinct report for the data managers to facilitate communication with the site to reconcile and update data.

Additionally, constant communication between team members can bring to light common themes the clinical monitors are seeing during their visits, data managers are seeing through queries, and statisticians are observing during data preparation. This allows for early action which can minimize time spent at the end of the study to clean the data and lock the database.

One thing that has become abundantly clear is that a risk-based approach to clinical trials requires close collaboration between disciplines. Data managers, clinical monitors, and statisticians must work together in ways they have not in the past. Traditional models that rely on functionally-aligned silos will not allow risk-based approaches to succeed.

Webinar: Clinical Research Statistics for Non-Statisticians

4 Regulatory Considerations for Using Social Media in Clinical Trial Patient Recruitment

Posted by Brook White on Thu, May 21, 2015 @ 10:56 AM

kristin-headshotKristen Snipes, Project Director

Social and digital media can be powerful tools for recruiting clinical trial participants and speeding up enrollment; however, there are several regulatory as well as operational considerations you need to keep in mind.  Here are some important ones:

IRB Approval

IRB approvalSocial media and digital media can have a much more informal feel than traditional advertising venues, like a newspaper or radio ad. While most of us would ask someone else to review anything we wrote for a newspaper, most of us don’t ask anyone before we post something on Facebook or Twitter. From a regulatory perspective, however, these two activities are the same if they are being used for patient recruitment. If it is visible by potential patients, you should assume it will need IRB approval and plan accordingly.

Depending on the type and format of social and digital media you are using, you will need to give some thought to how you will present the information to an IRB. For example, if you are promoting a study through Google AdWords, you will need to be able to provide the text of the ad and a static view of the page to which the ad will direct traffic. For a Facebook ad, you will need to include the text used as well as any images and links that are included. A web page will require a visual of the page layout, text included as well as any links provided to the subjects.

Sponsor Perceptions and Approval

Make sure the study sponsor is on board both with what information will be shared in the recruitment process and how it will be shared.  Social media potentially has a very broad audience and once you’ve posted something you have much less controlled with how it will be shared and distributed than you do with traditional media.  Sponsors may be less comfortable with providing detailed study information through social media channels than they would, for example, a poster designed for doctors’ offices.  The information posted on Clinicaltrials.gov is a good starting point as it will contain information the sponsor is comfortable sharing externally. Use of web pages and other social media can raise questions about the ownership of data and the restriction of access in a public domain.

Use Caution with Patient Provided Information

warningIf you social or digital media plans include collection of patient information (even if there is a potential that patients will submit data), you need to be particularly careful.  Two important questions to ask are what information are you collecting and how will you use the information.  Avoid collecting anything subject to HIPAA and be careful that nothing they submit would require informed consent.  In some cases, you may find that a process that is less efficient is still the way to go.  For example, rather than collecting information through a web form that is then submitted to sites, you may want to direct the patient to contact a site directly or use a call center with appropriately trained personnel.  This plan will also require review and approval by IRBs.

Picking an Agency

Sometimes CROs and sponsors don’t have the necessary expertise in-house to set up a social or digital media campaign, so it makes sense to outsource some of these activities.  If this is the case, you will likely be better off using a recruitment vendor that offers social and digital media services than a traditional ad agency.  If you do go with an ad agency, make sure they have experience working in regulated industries.

Free Webinar: Selecting Inclusion/Exclusion Criteria for Your Next Trial

4 Benefits of a Non-Regional Clinical Monitoring Strategy

Posted by Brook White on Thu, Jul 17, 2014 @ 05:06 PM

don't assign clinical monitors by geography

If you ask most CROs and Sponsor companies how clinical monitors (CRAs) are assigned to clinical study sites, the answer will be consistent: geography. Traditionally, CROs have employed a regional monitoring strategy for clinical trials, meaning a set of regionally-based CRAs (who often work remotely) are assigned to clinical study sites in their region. The main benefit of this model is a potential reduction in travel time and associated costs, since CRAs live and work in the same region as the study sites.

While travel related cost savings can be compelling, it’s important to consider the entire picture. In a traditional regional model, CRAs are often assigned to multiple studies at any given time, are required to handle grueling travel schedules with multiple site visits a week, and are forced to cope with the challenges of working remotely. Job satisfaction, monitoring quality, and project team cohesiveness can suffer and leave us wondering if there are alternatives to the regional model.

One viable alternative to the traditional regional model is a non-regional monitoring strategy. In a non-regional model, CRAs work in a central location (e.g. in the CRO’s local area) and are assigned to studies based on therapeutic expertise and availability, instead of geography. As a rule of thumb, for a typical Phase II study, 1 CRA is assigned to 8 to 10 study sites. Site assignments are made with efficiency in mind—one CRA might be assigned to all sites in a particular area of the country to allow for visit looping. There are many potential benefits to this alternative model, and we list four of the most significant benefits below:

1.  Increased monitoring efficiency and quality

In a non-regional monitoring model, CRAs are assigned to protocols and sites based on experience, not location, which means that CRAs can be assigned to fewer protocols simultaneously (preferably just one protocol). This model allows CRAs to be true experts on their assigned protocol(s), instead of juggling several different protocols. Protocol-focused CRAs are able to provide higher quality monitoring and better attention to their study sites. This model also reduces the number of CRAs that are needed to monitor a study and leaves the project team with a smaller, more focused team, which reduces administrative costs and leads to a more cohesive team.

2.  Reduces CRA burnout

CRA burnoutOne of the most reported causes of work-associated stress for CRAs is the need to juggle multiple protocols, which is a necessity in the traditional regional model.  CRA burnout can have significant cost and time implications for clinical trials, negatively affect monitoring quality and efficiency and team dynamics can suffer.  Using the non-regional monitoring model allows CRAs to focus on fewer priorities, which leads to more engagement and less burnout.

3.  Better project team integration

team integrationIn a non-regional monitoring model, CRAs are more fully integrated into the project team, both logistically (e.g. either working in the same office or able to easily attend meetings in the office) and functionally (e.g. being a true expert on one or two projects). This structure provides a sense of belonging, better team cohesiveness, more efficient meetings and increased ownership. Overall, this model contributes to CRA job satisfaction and a greater loyalty to the company, which often results in better CRA retention rates.

4.  Better set-up for risk-based monitoring

As the industry moves toward risk-based and centralized monitoring, it will be more critical than ever that CRAs work closely with the rest of their project team. Specifically, they will need to have strong relationships and seamless handoffs with project team members in data management and biostatistics who can assist with some of the strategies necessary to successfully implement a risk-based strategy. This type of team integration is more feasible in a non-regional monitoring model.

The clinical trial monitoring landscape is changing right now. The FDA’s recent issuance of its “Guidance for Industry:  Oversight of Clinical Investigations—A Risk-Based Approach to Monitoring” demonstrates that the industry’s traditional approach to clinical monitoring can be re-configured in favor of more agile, efficient, and creative strategies. A non-regional monitoring model has the potential to increase the quality and efficiency of monitoring while increasing overall CRA job satisfaction and project team cohesiveness. 


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