outstanding sites - imarc...examining the publication and podium presentation history of the...

Selecting investigators and sites is a very important and underrated part of the clinical research process as

many factors depend on those individuals navigating the day to day of the journey to approval, including:

1 www.imarcresearch.comW E ’ L L E A R N Y O U R A P P R O V A L .

Introduction

Selecting sites is the responsibility of the sponsor as outlined in ICH-GCP 5.6.1, 21 CFR 812.43, 21 CFR

312.50, and ISO 14155:2011(E) 5.8. All require that the investigator be qualified by training and experience

and have adequate resources to conduct the study. In many cases, sponsors collect Curriculum Vitaes and

Medical Licenses as a means to verify qualification and experience, and generally speaking, a tour of the

facility and an introduction to the various key staff members who will be participating in the clinical study is

conducted by the sponsor to verify the adequacy of the site and resources.

The Federal Regulations do not provide any further details or guidance for the sponsors in selecting

outstanding sites or additional requirements to ensure sponsor compliance in site selection. It is truly

the sponsor’s responsibility to take the time at the start of a study to carefully examine potential sites

and ask important questions during their review process. Rushing through the site selection process

S e l e c t i n g Outstanding sites

out·stand·ing – an adjective meaning; Standing out or superior among others of its kind; prominent; distinguished.

Patient recruitment, informed consent, liaising with family members, care takers, and other medical professionals, data collection and submission

Reporting to the sponsor and providing pertinent information as it relates to the study and the patients, communicating with the iRB, product accountability


could potentially leave the sponsor stranded and lead to costly delays in product approval. Patient

protection could be compromised and the data left incomplete, unreliable or not suitable to analyze.

In addition, selecting sites that do not have an established high level of study execution could cost

the sponsor additional time and resources for various reasons, including:

• May need to increase training and/or monitoring efforts in response to repeated non-compliance or a demonstrated lack of knowledge regarding gcP requirements

• May need to add additional sites if those selected fail to enroll adequately or fail to produce evaluable data

• Anticipated enrollment timeline may be extended due to sites not having an adequate patient population to meet the needs of a study

Today’s clinical research landscape typically allows for minimal resources under tight timelines, requiring

sponsors to quickly, yet effectively decide which sites are the right fit for the job. Sponsors, ideally, want to

select outstanding sites, so that they are not left stranded in the middle or at the end of a study. Having a

procedure in place to guide them is critical to ensuring adequate site assessment. Incorporating the

OUTSTANDING acronym, as described below, into your site assessment procedure may be one

step forward in ensuring high performing, compliant sites.


An organized site has well established systems for the key functions of executing a research study such as;

4 Training staff

4 Recruitment

4 Obtaining informed consent

4 Ensuring protocol compliance

4 Maintaining study related documents

4 Communicating with

• Subjects

• Sponsor

• Study Staff

• iRB

Organization is a tricky element to examine, as it may mean different

things to different people. From a sponsor’s perspective, just asking a site

what their standard operating procedures are for the above items may be the gateway into understanding

a site’s level of organization. If the site does not have standard operating procedures for research, this may

be a warning sign for the sponsor. Perhaps the site has a proficient system for obtaining informed consent

but has unkempt regulatory binders. Identifying this potential weakness at the start of the study provides

the sponsor with awareness. This awareness can allow for detailed planning for additional monitoring

focusing on regulatory maintenance support.

A site may have detailed, written procedures that they are eager to provide the sponsor. More importantly,

is the site aware of what these procedures are or do they know when the procedures were last updated

or if recent changes were made? A discussion with key study personnel focusing on standard procedures

will also give the sponsor a glimpse into the organization and preparedness of a site.

A sponsor should pay close attention to sites that have multiple locations. By what means does the

staff communicate between locations? The sponsor may want to visit all locations during the selection

process to establish if the organization and standard operating procedures are uniform across locations.

It may be helpful for the sponsor to step through the doors of the locations first as a patient, and then

from the perspective of a monitor during a site visit. Are the multiple locations helpful for the patients

to follow-up during the study or are the multiple locations a source of confusion that might lead to

decreased patient retention? For monitoring visits, where will study related documents be stored and

how will the monitor obtain access?


Execution of a successful clinical research study takes hard work from a study team working together to

protect the patients and produce quality data. Prior to the sponsor teaming up with the investigator and

the site, the research team at the site must be unified and operating with high efficiency and clear, well

defined roles and responsibilities. Leading every team is a strong captain, or lead research coordinator/

research manager. Does the site have a lead contact with whom the sponsor can easily communicate?

How many other coordinators is this lead coordinator responsible for updating on the status of the study or

changes in the protocol? Does the site have multiple Co-Investigators or just a Principal Investigator? Where

are the coordinators located in relation to where protocol-related procedures are conducted or in relation

to the physicians’ offices? Does the site have separate staff for IRB communication and scheduling, and

how is pertinent study-related information communicated to them? Most importantly, is there a sense of

accountability at the site? Accountability to:

4 The patients

4 The study

4 The study team

4 The sponsor

It may be appealing to a sponsor to select a site that has a large staff that can seemingly meet the

requirements of the protocol. However, if the team is not operating effectively, this can lead to a

breakdown in communication between staff members resulting in multiple protocol deviations, poor

treatment of the subjects, and delayed reporting to the sponsor and IRB.


A sponsor can use the site selection process to determine the site’s institutional requirements for

training research staff and then ensure that all staff members that will be participating in the study have

received the training and are up to date on any continuing education required by the institution or IRB.

The sponsor can also collect CVs of staff in addition to the investigator to determine if the staff has

previous training that is relevant to the study and therapeutic area. Clearly, a psychologist would not be

a considered for a study that involves an endovascular procedure. However, what about a psychologist

as a principal investigator of a psychological pharmacological study? Is that appropriate, is that safe?

The sponsor should first consider the nature of the study, focusing on the study procedure and risk to

the subject. If the procedure is standard of care routinely performed in clinical practice and the study

is asking for several additional data points to be captured, the specific training or background of the

physician may not weigh as heavily in the sponsor’s decision.

Another important consideration often overlooked by sponsors is the therapeutic area interest and

experience of the support study staff, for example: the research coordinators/research nurses. The

PIs may have been working with these nurses for 10 years with great success, but when it comes to

capturing detailed data points specific to the nature of the study, nurses may not have been exposed

to that area of medicine since nursing school. This doesn’t mean the sponsor does not select the site

or that the site is not outstanding. It just may require the sponsor to conduct more therapeutic area

specific training prior to initiating the study at a site.

Examining the publication and podium presentation history of the investigators is also an excellent

way of determining their experience with research in general and their interest in the therapeutic

area under investigation.

During the selection, sponsors can also collect current licensure or documentation of continued

education from:

4 Physicians

4 Nurses

4 Physician Assistants

4 Technicians or Allied Health Professionals affiliated with the study


The first step in determining staff is very basic - who is the Principal Investigator (PI) and to whom and what

responsibilities will he/she delegate? Some sites have several physicians that divide principal investigator

responsibilities between several studies. There is one Principal Investigator and all other physicians are

then co-investigators.

Next step - coordinators. It is not entirely uncommon for a site to have the PI (or a co-investigator) fulfill the

coordinator role. But will this work for your study?

Consider the more common scenario, several coordinators:

4 Is there a lead coordinator with back-up coordinators or do the coordinators share equal responsibility in study-related procedures?

4 Do the coordinators have other non-research responsibilities? If yes, how much time can be dedicated to this study specifically?

4 What is the typical research protocol load of the coordinators?

4 Is the coordinator responsible for study recruitment?

4 Who communicates with the IRB? Is it the study coordinator or is there a specific IRB coordinator?

4 How does the site allocate study back-up personnel?

4 What about technicians for imaging? Is the site using the hospital staff or are there dedicated research technicians?

Asking the site the questions above and truly considering the answers related to the needs of the study

will help identify potential issues. It may be that the research coordinator is overwhelmed and stretched

thin, deep into a study with too many subjects already. This could result in incomplete data that is loaded

with protocol deviations and submitted beyond agreed upon timelines.


Time and cost are important considerations when selecting sites. During the site selection process, the

sponsor can ask the following questions to determine the differences in time and cost between sites so

that the sponsor can compare apples to apples.

4 When can the study begin at the site?

• time from iRB submission to approval

• time to negotiate budgets and other legal considerations

• Staff availability to provide study start-up essential documents

• Study initiation training or meetings

4 When can the study be completed at the site?

• Potential pool of subjects for recruitment

• Staff dedicated time for research recruitment

4 What are the budget considerations?

• Research supported in a revenue neutral manner or as a for-profit center

4 How will the site bill and how will the sponsor pay?

• Understand research related procedures vs. standard of care procedures at the site and then obtain site specific costs for research related procedures

• Discussion of how payments to the site will be made paying special to the following;

• evaluable data

• Screen failures

• lost-to-follow-up subjects

• Payment schedules


Take a tour! If you have the opportunity of visiting the site during the

selection process - tour it! Start from the parking garage

or main door. Imagine you are a subject and you are

visiting this doctor’s office for a study visit.

If you don’t have the luxury of visiting, the same questions

can be asked by the sponsor:

Where does the subject park in relation to where the follow-up procedures will be conducted?

Is the site location easily accessible considering the patient population?

Consider a study for subjects with venous leg ulcers, a condition causing great discomfort in walking long distances. Would an ideal site be one that the subject must park and walk a half mile to the clinic and then climb stairs to get to the doctor’s office?

Take a close look or ask for a detailed description of the procedure rooms and exam

rooms/offices for follow-ups.

4 Confirm the number of each of these rooms available for research use. Inquire about the times that research subjects will be seen by study staff.

4 Confirm that the number and available times meet the needs and expectations of the time and events table of the protocol.

4 Confirm the site has adequate storage for study supplies and that the site can maintain security of the investigational product according to the sponsor’s requirements.

4 Confirm where study testing will be obtained. Does the site have a research lab, research radiology department? If the site is using the hospital labs/departments, inquire how the staff ensures that the testing is obtained according to the protocol requirements.

4 Confirm where monitors will review study related documents.

4 Confirm the location of and compliance with privacy for subjects when informed consent is obtained.


The experience level of the research staff can be both beneficial and a challenge, no matter where the

staff member sits on the experience continuum. Understanding the different levels of experience with

the study staff can help sponsors identify strengths and weakness of a study team.

Newer study staff:Challenge: A sponsor may tailor certain trainings toward newer research staff or provide additional

support via telephone calls or monitoring visits. This may take additional time and resources at the

beginning of the study.

Benefit: A sponsor may see the eagerness of newer staff to learn and the opportunity to introduce

the sponsor’s preferred method of conducting research as a benefit.

Experienced study staff:Benefit: The coordinator is well versed in the Federal Regulations and GCP. These coordinators

often have systems in place for executing clinical protocols.

Challenge: “But this is the way I have been doing it for 20 years.” At times, well experienced

coordinators are not as open to different or updated ways of executing clinical protocols. Take electronic

data capture as an example. Coordinators with years of experience are accustomed to paper based case

report forms. These coordinators may not welcome electronic data capture and might take extended

periods of time to enter data and resolve queries.


Everyone has a reputation-whether good or bad, personal or professional. Sites also have reputations.

Their reputation is supported by the quality and timeliness of the data submissions. As the sponsor, it is

your job to find sites with a good reputation. A site that is known for good, clean data that is submitted

in a timely matter with minimal queries has a good reputation. How do you find out if a site has a good

data reputation?

Ask the site! No one is going to tell you - “I don’t turn data in on time and my monitor visits are filled with queries and sticky notes”. However, asking these questions can help you gauge the site’s data quality:

• What do you use for source documents at your site?

• Do you have electronic or paper medical records? Does the monitor have access to these records during visits?

• Do you review medical records for adverse events? How and how often?

• Some sponsors have tight turnaround times for data entry- what is your typical turnaround time from visit to entry?

• Is the same person who is capturing source data entering the data into the CRF?

• Do you have a quality assurance system for reviewing your data?

• Describe a typical monitoring visit to me? About how much time is spent sitting with the monitor resolving queries or addressing source document clarifications?

• If you exceed sponsor agreement data submission timelines, what is your course of action?

• If you experience high enrollment for this study, do you have a plan in place for maintaining data submission timelines?

• How do you make corrections to your source documents and CRFs?

• This study has ____ expected turnaround timelines for data. Are you able to reasonably meet this expectation?

• Can I borrow your white-out?

Clearly, the last question is a trick (white-out is a no-no in clinical research!!). But asking “about”

their data may give the sponsor a snap shot of the quality of work a site is producing.


Begin by establishing if the site intends on utilizing a local or central IRB. Next, confirming if the primary

coordinator will be responsible for IRB activity or if the site has a dedicated IRB coordinator will help

the sponsor identify the workload of the primary coordinator or assess study specific training needs

of the IRB coordinator. Noting how often the IRB meets, collecting a membership list and reporting

policies for adverse events and non-compliances will help the sponsor ensure the site is compliant

with IRB requirements and confirm that the site is operating under an IRB that is 21 CFR 56 compliant.

In addition to collecting the policies and procedures, the sponsor may consider querying the site

staff to gain a sense of the personnel’s familiarity with the IRB requirements. If the IRB has specific

requirements for obtaining informed consent, confirm the site has processes in place that documents

compliance with the requirements.

By gaining a sense of IRB functioning, the sponsor can appropriately establish timelines for initial study

submission, expected review and approval turn-around time, requirements for on-going study review,

and reporting policies and procedures.

For most studies the number one challenge is recruitment. Sponsors spend hundreds and thousands of

dollars in marketing materials and third party marketing groups to boost and maintain enrollment numbers

during a study. Identifying OUTSTANDING sites with a large population of appropriate patients for the

study can save the sponsor money and time during the study. For example, a pharmaceutical company

that is conducting a study for 6-12 year old age group with attention deficit hyperactivity disorder would

not target areas that have a high retirement age population. It is unlikely that even the retirees

would have children in that age range. The Sponsor should approach physicians that have

a strong practice in the therapeutic area of interest which can

demonstrate their ability to recruit patients or who are likely to

get referrals from practice patients that have received good

care. If your company has a sales team, start there. The

sales people are on the front line and can provide you

with valuable information on the physicians that use your

company’s products often and with good outcomes.

Lastly, the sponsor should consider the size of the hospital

or physician group in relation to the recruitment goals of the site.

For more information on how you can help prepare your sites for a better outcome, starting from Day

One, please contact John Lehmann at 440.801.1540 or via e-mail at [email protected].

22560 Lunn Road, Strongsville, Ohio 44149 • tel 440.801.1540 • fax 440.801.1542

[email protected] • imarcresearch.com

W E ’ L L E A R N Y O U R A P P R O V A L .

Jacqui Lingler, Clinical Research Associate

Jacqui joined IMARC in 2011 and has over nine years of clinical research experience. Having worked many years at an investigative site, Jacqui understands and appreciates the importance of the Research Coordinator and their impact on compliance. In addition to monitoring on several clinical trials, Jacqui has also provided training to project managers, research coordinators and new monitors on various topics in regulatory compliance.

Jacqui holds a Bachelor of Science degree in Psychology from John Carroll University, OH. She is also a member of the Society of Clinical Research Associates (SoCRA). Additional writing/support provided by Brandy Chittester, Mary Lewis, and Sandra Maddock.

Research the researchers! Check FDA warning letters for potential PI and Co-I names and reasons that

they received warning letters or who were otherwise restricted in their research activities. Talk with your

sales staff. As mentioned earlier, these are the individuals on the front lines that are interacting with the

physicians regularly and can offer insight into the relationships that the PIs and Co-Is maintain with their

staff and patients. Also as mentioned earlier, reach out to colleagues in the industry that may have an

established relationship with the site and the physicians and identify any potential challenges that may

be presented working with the PI or the Co-Is.

Selecting outstanding sites is key in running a well-controlled clinical trial. Failure to identify outstanding

sites could result in added costs and could lead to delays in bringing much needed products to the

bedside. The upfront work put into site selection will likely yield a positive return. Going beyond a phone

call or an email survey by visiting the sites, doing the research on the institutions, and evaluating them

on the OUTSTANDING continuum will not only help sponsors fulfill their regulatory obligation to select

qualified and experienced sites, it will help them SELECT OUTSTANDING SITES.

outstanding sites - imarc...examining the publication and podium presentation history of the...

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