Who does What in Clinical Research?

WHAT position should I be applying for? WHERE should I be applying? Pharmaceutical companies? Hospitals? CROs? Wait, what is a CRO?

Sound familiar?  These were the exact questions I was asking when I was first introduced to the field of Clinical Research.  Don't worry, I've got you covered!  But to answer these questions we first have to know the "who does what" in Clinical Research?


So let's try to break it down first with some definitions.

Sponsor

ICH GCP E6(R2) Section 1.53 defines a Sponsor as "An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial."  So in most cases these are pharmaceutical, biotech and/or device companies who initiate a clinical trial using their drug or technology, but they don't actually conduct the investigation themselves, as in they don't actually treat the subjects themselves. 

Investigator

ICH GCP E6(R2) Section 1.34 defines an Investigator as "A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator."  So, Investigators are selected and contracted by the sponsors to run the clinical trials at their trial sites.  The Principal Investigator (PI) may delegate trial related activities to members of his or her clinical team, but is ultimately responsible for all trial related activities at the site.  There may also be some cases where the Investigator is also the sponsor.

Trial Site

ICH GCP E6(R2) Section 1.59 defines a Trial Site as "The location(s) where trial-related activities are actually conducted."  For instance a Trial Site is where patients go to receive their clinical trial treatment - hospitals, clinics, private physician's offices, or institutions. 

Trial Subject

ICH GCP E6(R2) Section 1.57 defines a Trial Subject as "An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control."  In oncology trials, "control" refers to the standard of care (SOC) treatment for the patient's cancer, or some sort of combination therapy with the investigational drug.  Placebo ("sugar pill")-controlled trials are uncommon in oncology trials, as it would be considered unethical if a SOC already exists for the subject.  Remember, the number one focus of any clinical trial is human subject safety!

Regulatory Authorities

ICH GCP E6(R2) Section 1.49 defines Regulatory Authorities as "Bodies having the power to regulate.  In the ICH GCP Guidelines the expression Regulatory Authorities includes the authorities that review submitted clinical data and those that conduct inspections.  These bodies are sometimes referred to as competent authorities."  Each country has their own regulatory authorities, examples listed below, each with their own nuances and complexities around clinical trial start-up all the way through investigational drug approval, and beyond to post-market surveillance. 

  • US: Federal Food and Drug Administration (FDA)
  • EU: European Medicines Agency (EMA)
  • Japan: Pharmaceuticals and Medical Devices Agency (PMDA)
  • UK: Medicines and Healthcare products Regulatory Agency (MHRA) 

Institutional Review Board (IRB)

ICH GCP E6(R2) Section 1.31 defines IRBs as "An independent body constituted of medical, scientific, and non-scientific members, whose responsibility is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial by, among other things, reviewing, approving, and providing continuing review of trial protocol and amendments and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects."  This sounds very broad, but the IRBs apply the regulations and guidances of the Regulatory Authorities to oversee that the Investigator and the Trial Site are compliant in conducting the clinical trial.  IRBs are ultimately responsible for safeguarding the rights, safety, and well-being of all trial subjects. 


Here's a simple diagram of how they all interact together.

 Regulatory authorities provide the overarching regulations and guidances for the Sponsor, IRB/IEC, Investigators and their delegates.  The sponsor and Clinical Site work harmoniously to ensure trial subject safety, protocol compliance and data integrity.

Regulatory authorities provide the overarching regulations and guidances for the Sponsor, IRB/IEC, Investigators and their delegates.  The sponsor and Clinical Site work harmoniously to ensure trial subject safety, protocol compliance and data integrity.

 

Ok; so we have the basic definitions, now let's talk about the players on the sponsor side and the trial site.  Note that these are generalizations since every company and institution will have their own naming convention and organizational charts.   Also note that my experience is in Oncology research, so the information below will be geared towards sponsors and trial sites involved in oncology clinical trials.  Much of the information will apply to other therapeutic areas, but there may be some nuances. 


Sponsor

Clinical Operations (ClinOps)

Like the name suggests this department is responsible for all things operational through planning, start-up, conduct and close-out of clinical trials.  They manage the day-to-day activities and is usually the largest and most dynamic group, but then again I'm biased!  Often times called "ClinOps" or just "Ops", doesn't it have a nice ring? :) Below is a general list of common positions found within ClinOps, which of course will vary from company to company, but hopefully it'll be a useful starting point.

Clinical Research Associate (CRA)

CRAs are responsible for interfacing with the site.  For many studies CRAs may be the "face" of the sponsor since they may be the only ones who the sites will ever see during their visits.  Think of them as a "dual agent" since they're a conduit of information from the sponsor to the site, and in turn, from the site back to the sponsor.  Their major responsibilities may include to:

  • Monitor the progress of the study at sites by providing site management and clinical monitoring of data
  • Ensure that all personnel at the site are aware of their obligations and that they are conducing the trial within the protocol, sponsor, GCP and applicable regulatory guidances
  • Ensure that the site is equipped with adequate supplies and investigational product to conduct the trial per protocol requirements.

Aren't there different types of CRAs?

Yup!  To make it even more confusing, there are differences even within the CRA role.  Some are considered "in-house" CRAs and others may be called "regional" CRAs or "monitors".  The difference is that in-house CRAs, like the name suggests, are located in-house and perform duties from the sponsor location and only occasionally visit the trial sites.  So they perform all of the tasks of a CRA but without having to go to the trial sites on a routine basis.  Regional CRAs, or often times just called monitors, are the "road warriors" and are constantly on the road traveling to various trial sites in their region. 

Different companies have different models for their clinical monitoring and some prefer to have both in-house and regional CRAs.  In this case the in-house CRAs may be tasked with more of the site management piece and communication with the sites, and the regional monitors are tasked with going to the sites to perform the Source Data Verification (SDV) and reviews of Investigational Medicinal Product (IMP) and regulatory documents.  Or, another model is to have only regional CRAs/monitors, in which case they take on all responsibilities for the site including site management, SDV, etc.  Some sponsors outsource the monitoring/management of sites all together to Contract Research Organizations (CRO).  More about this later.

Clinical Project Manager (CPM)

CPMs are pretty much responsible for the overall execution of the trial and manage the entire operational piece from start-up to close out.  They are also a source of information to the Trial Sites, but the information is usually delivered through the CRA.  Key responsibilities include to:

  • Oversee CRA activities and ensure Trial Site oversight/management is adequate
  • Collaborate with cross-functional groups (Data Management, Regulatory, Product Safety, etc) to execute/manage/develop protocols
  • Manage Trial Site contracts and budget negotiations
  • Manage study timelines, budgets and deliverables

Clinical Trial Associate (CTA)

CTAs provide administrative support to the CPM and CRAs on various study-related tasks such as to:

  • Maintain Trial Master Files (TMF)
  • Maintain Clinical Trial Management Systems (CTMS)
  • Create/maintain trackers for study management
  • Draft meeting minutes and coordinate clinical study team meetings

Document Specialist

Responsible for supporting paper/electronic-based TMF activities

Usual job duties include to:

  • Maintain the clinical document storage room
  • File and maintain paper TMF documents per defined structure
  • Scan paper TMF documents to the electronic TMF (eTMF) system
  • Ensure document version control and maintain revisions

Clinical Development/Medical Affairs

The name of this department depends on the "stage" of the company.  As in, usually if a company has a drug already approved in the market the department will most likely be called Medical Affairs.  If not, companies may call it something else like Clinical Development.  But overall the purpose of this group is to oversee the medical aspects of the trials with regard to subject safety and strategic clinical planning within the market space. 

Medical Monitor

Are MDs who provides medical oversight and clinical development expertise to the study team.  They interact with the Investigators to:

  • Discuss Trial Subject safety management
  • Assess adverse events and their relationship to the investigational product
  • Analyze safety and efficacy data for scientific reports

Medical Science Liaison

Are typically MDs (but some are also PhDs or PharmDs) who establishes and maintains collaborative relationships with Key Opinion Leaders (KOL) and Investigators out in the field conducting the clinical trials.  They're sort of like your pharmaceutical sales reps in that they promote and advertise the clinical trials and development for the company, but they have a strong understanding of the scientific merits of the drug and the emphasis is on the exchange of scientific information and training. 

Product Safety/Pharmacovigilance

The name of this department may also depend on the stage of the company, but whether or not they have a drug approved the group serves to manage all aspects of adverse event monitoring and reporting per regulatory regulations.  They ensure safety data are comprehensive, accurate and are maintained in the clinical safety database.  Below are couple positions.

Product Safety Coordinator:

  • Ensure proper safety data reporting per reporting requirements
  • Assist with Serious Adverse Events (SAE) reconciliations
  • Maintain clinical safety database

Product Safety Physician:

  • Review clinical safety data and collaborate with Medical Monitors to review/determine impact on trial protocol. 
  • Analyze safety data for continual monitoring and updates to study documents: Protocols, Informed consents, Investigator Brochures, etc

Data Management (DM)

This department is ultimately responsible for the quality and integrity of the clinical data entered into the database by the Trial Site.  Although ClinOps plays a large role to facilitate proper data entry at the Trial Sites, as well as data cleansing activities, the Data Management group is ultimately responsible for the clinical database and data management activities, timelines and to drive the processes forward.  ClinOps and DM work closely with sites to ensure data integrity.  Below are some common positions.

Data Manager:

  • Design/validate/maintain clinical database
  • Review data in clinical database with regard to quality and integrity
  • Generate queries to the site regarding non-conformant data or data requiring clarification
  • Train site personnel and provide data entry guidelines

Entry-level data entry positions within DM may also be an option for those interested in ClinOps.  I've heard of many Data Managers becoming CRAs and even vice versa. 

Statistician:

  • Responsible for all statistical aspects of the clinical protocol
  • Analyze and report on clinical trial data
  • Provide statistical consultation for clinical protocol design, conduct, efficacy evaluation and data review

Regulatory Affairs

Group responsible for liaising with the regulatory authorities.  Manages all aspects of compliance and submissions from initiation of study to conduct to application of market approval.  Often also called RegOps.

Regulatory Coordinator:

  • Prepare/assist submissions packages for regulatory authorities
  • Author/review study documents such as Protocols, Informed Consents, Investigator Brochures, etc.
  • Review study- and site-level regulatory documents for completeness/accuracy per regulations/guidelines

Entry-level positions within RegOps may also be a means of getting your foot in the door!  Their interactions with ClinOps and familiarity with regulatory documents will definitely be transferable skills.

Quality Assurance

Responsible for ensuring a trial is conducted per regulations and guidelines put forth by the regulatory authorities, and per company Standard Operation Procedure (SOP).

Clinical Quality Assurance Manager:

  • Author/review SOPs
  • Assist/conduct study/site audits
  • Serve as resource for study team with regard to compliance per regulations/guidelines

Trial Site

Even more so than the sponsor side, the trial site has more variations in terms of how they are organized. This is partly because there are so many different types of Trial Sites.  For instance, some are university hospitals, others may be community hospitals, or some may be private clinics dedicated solely for the purposes of clinical trials.  And these differences affect the way the trials are initiated and conducted at the sites, which I can go into detail in another post…  Below is a list of some key roles at the Trial Sites.

Principal Investigator (PI):

Investigators are ultimately the sole responsible person at the trial site.  And because it is rare that a trial is conducted by only one investigator, there is a distinction between the Principal Investigator (PI) and the Sub-Investigators (Sub-I).  The PI is ultimately responsible for the trial, which means although he can delegate work to his team, he is the accountable person!

Sub-Investigator (Sub-I):

Sub-Investigators are part of the study team at the site who have been delegated a defined set of tasks by the PI to support various aspects of the trial.  So does this mean anyone who is delegated a task is a Sub-I?  Well, not quite.  To be a Sub-I, one has to be listed on the FDA Form 1572; and yes, the FDA does provide guidance around who should be listed as a Sub-I, but there are definitely different interpretations.  Ok, now I'm rambling, this topic will have to be an entirely different post!  

Clinical Research Coordinator (CRC):

Key part of the study team, and an entry-level position I highly recommend!  They pretty much do the day-to-day activities of managing and running the trial at the site per the protocol and within local guidances, and interacts closely with the sponsor's CRA.  This means they do everything from scheduling patient visits for required assessment per the protocol, to serving as a liaison for information from the sponsor to the study team, to addressing queries from the sponsor and vendors, to coordinating regulatory requirements by the sponsor, and in some institutions they even enter the study data into the sponsor's clinical database.  Some institutions hire CRC's with nursing degrees so they even provide the patient care.  

Data Manager/Entry Personnel:

They have the sole responsibility of entering patient data collected by the clinical team, and entering it accurately and timely into the sponsor's database.   They interact with the sponsor's CRA and the Data Manager to resolve any queries or address any concerns around the data.  This is also a great entry-level position since although you are not directly involved in the data collection or the day-to-day activities, you are still close enough and can familiarize yourself with the protocol, the procedures, and the fundamentals of running a trial. 

Study Nurse:

So some sites have nurses who are their CRCs, but for other sites they have a separate Study Nurse.  So they pretty much do all of the patient care aspect, within their scope of practice of their nursing degree - pretty much like the PI/Sub-I's right-hand person!  Some sites might even list them as a Sub-I.   

Regulatory Manager:

Counterpart of the Regulatory Affairs personnel on the sponsor side.  They liaise with the sponsor to provide and maintain the required regulatory documents.  They are responsible for meeting the regulatory requirements of the sponsor, the IRB and the regulatory authorities. 


That seemed like a lot!  I hope this helps to give you a better sense of the various positions within clinical research and their roles, and how they may differ from the Sponsor side and the Trial Site.  Below is a simple diagram to tie it all together~

 The teams on the Sponsor side and the Clinical Site work together to ensure trial subject safety, protocol compliance and data integrity. 

The teams on the Sponsor side and the Clinical Site work together to ensure trial subject safety, protocol compliance and data integrity. 


So now we know what the roles and responsibilities are for positions on the Sponsor side and at the Trial Site, but what are CROs? 

Contract Research Organization (CRO)

Many sponsors outsource their work to Contract Research Organizations (CRO).  A CRO is a company which holds a contract with the sponsor to perform work on their behalf.  The sponsor can outsource any or all activities ranging from protocol development to monitoring to statistical analysis.  When the obligations of the sponsor are transferred to a CRO, the CRO becomes responsible, from a legal and regulatory standpoint, for fulfilling the obligations. 

The most common activity outsourced to CROs is clinical monitoring.  Which means you can be a CRA working for a sponsor or for a CRO - even more options!  I won't list the positions within CROs since they essentially mirror those of the sponsor side, which makes sense since they are doing work on their behalf and will have a similar organizational structure.  So, CROs are also great sources for entry-level positions!  

 

 CROs are contracted by sponsors to do work on their behalf, which means it is another great source for jobs in Clinical Research!

CROs are contracted by sponsors to do work on their behalf, which means it is another great source for jobs in Clinical Research!

Hope this post wasn't too dry!  I remember being so confused and lost about the various positions within clinical research during my job hunt, and I hope this may add value to anyone also on the hunt!  I hope it gives you a sense of what the groups are and what they do.  Use it to your advantage on your hunt for entry-level positions.  For instance, if you find that you are interested in the functions of Regulatory Affairs, try Googling: "Entry-level positions in Regulatory Affairs".   Or my favorite, try to find someone you know in that field - a friend, a friend's friend, or a colleague… and ask them for an Informational Interview to learn more about what they do!

Remember, stop Analysis-Paralysis and TAKE ACTION!

If you enjoyed the post, please hit that like button and feel free to share with someone you think may enjoy!  See you in the next one~

Thanks for reading! 😘

Cheers~

Jenny

PS: Did I forget to mention a group?  Or would you like more detail on a subject?  Feel free to leave a comment!  Would love to hear your feedback!  Let's get some discussions going!