What is Clinical Research?

 Research in which people, or data or samples of tissue from people, are studied to understand health and disease. Clinical research helps find new and better ways to detect, diagnose, treat, and prevent disease. Types of clinical research include clinical trials, which test new treatments for a disease, and natural history studies, which collect health information to understand how a disease develops and progresses over time. (1) 

How do Clinical Trials work?

It all starts with the Sponsor deciding to conduct a clinical trial on a study pharmaceutical drug, medical device or biologic. A sponsor is the organization or person who initiates the study and who has authority and control over the study. (2) The FDA defines a Sponsor as a person who takes responsibility for and initiates a clinical investigation. The sponsor may be an individual or pharmaceutical company, governmental agency, academic institution, private organization, or other  organization. (3) 

Depending on the type of test article, (Test article means any drug for human use, biological product for human use, medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the act or under sections 351 or 354-360F of the Public Health Service Act. (4)  , the sponsor will submit a Investigational New Drug Application (IND) for a pharmaceutical drug or biological product, a Investigational Device Exemption (IDE) for a medical device to the Food and Drug Administration (FDA) to begin clinical trials. In the United States, the FDA serves as the regulatory agency for regulating certain foods, drugs, cosmetics and medical products. In order for a pharmaceutical product, a biological product or class III device to be marketed, it must be granted approval by the FDA. For class I and class II medical devices, the FDA may provide a clearance (which is a form of an approval). 

 

Below is a list of the top 10 Pharmaceutical Companies (Sponsors)

  1. Pfizer - www.Pfizer.com
  2. Johnson & Johnson  - www.jnj.com
  3. Eli Lilly - www.lilly.com
  4. Sanofi - www.sanofi.com
  5. Novartis - www.novartis.com
  6. Bayer - www.bayer.com
  7. Roche - www.roche.com
  8. GlaxoSmithKline - www.gsk.com
  9. Merck - www.merck.com
  10. AbbVie - www.abbvie.com                                                                                                                                                                                             

    Drug Development Process

Clinical or Contract Research Organizations (CROs)

A CRO is an organization that is hired by the Sponsor to carry out certain clinical research responsibilities on behalf of the Sponsor. According to E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1), a CRO is a person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor's trial-related duties and functions. Although the sponsor is still obligated to oversee and manage CROs, outsourced trial related duties include project management, monitoring, site recruitment, medical writing, pharmacovigilance, data management, trial master file management and clinical study management just to name a few. 
Here are a few of the top CROs:
  1. IQVIA - www.iqvia.com
  2. PPD - www.ppd.com
  3. ICON - www.iconplc.com
  4. PRA Health Sciences - www.prahs.com
  5. Parexel - www.parexel.com
  6. Covance - www.covance.com
  7. Medpace - www.medpace.com
  8. Syneos - www.syneoshealth.com

 

Institutional Review Board (IRB)/Institutional Ethics Committee (IEC) 

An independent body constituted of medical, scientific, and nonscientific 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 thing, reviewing, approving, and providing continuing review of trial protocols and amendments and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects.5 
IRB/IEC approve the following: Principal investigator to conduct the study at their research site, clinical research protocols (A protocol is the written description of a clinical study. It includes the study's objectives, design, and methods. It may also include relevant scientific background and statistical information.2  (provided by the sponsor), Informed Consent forms, Advertisements (TV, Radio, Newspaper, anything used to recruit subjects for clinical trial participation). 

 

Clinical Research Associate (CRA)/Study Monitor

A representative provided by the study Sponsor to review and monitor subject study files to ensure subject safety, regulatory documents are up to date, perform drug/device accountability, source data review, source data verification, ensure site has enough study supplies and keep track of any staff changes at the site and ensure the site is following the protocol, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1) Guidelines and Code of Federal Regulations. CRAs perform 4 types of visits: Site Qualification Visits (to determine if the principal investigator and site is a good fit for the study), Site Initiation Visits (once the PI is selected for study by the sponsor, the CRA will train the PI and site on the study they are selected for) Interim Monitoring Visits (to monitor the study progress at the research site and to ensure subject safety once they have been enrolled in the study among other on site tasks and responsibilities) and Close Out Visits (to end the study at the site)

 

Principal Investigators (PI) 

Principal Investigators are typically medical doctors (MD) or doctors of osteopathic medicine (DO) that are selected by the sponsor (pharmaceutical company, medical device company or biotechnology company) to implement/execute the clinical trials at their clinical research site. According to clinicaltrials.gov, principal investigator is defined as...the person who is responsible for the scientific and technical direction of the entire clinical study2. In clinical research, a “site” is where the subjects will be seen for the clinical trial. A site can be at the PIs private practice, medical group practice or hospital.  

 Clinical Research Coordinator/Study Coordinators 

Clinical Research Study Coordinators assist the principal investigator in clinical trials. The PI is responsible for delegating responsibilities to the study coordinator (and other research study responsibilities to study team members). They are, most times, responsible for collecting informed consents, coordinating subject study visits, performing study related procedures, collecting and shipping laboratory samples and maintaining regulatory documents. Below you will find a sample schedule of events that the site will follow when it comes to subject visits.

Clinical Trial Participants/Study Volunteers/Subjects

Clinical trial participants (subjects) must qualify for a study before being enrolled in a study. The principal investigator or study staff will identify potential research participants and invite them to participate, this is called pre-screening. Once the potential research participant arrives at the study site, the subject will go through a screening process. If the subject has agreed to participate in the study, they will sign an informed consent form (that is IRB approved and provided to the subject by the site) and then will be evaluated to see if the subject meets the study requirements regarding the inclusion and exclusion criteria. 

Informed Consent Form (ICF)/Process: A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject’s decision to participate. Informed consent is documented by means of a written, signed, and dated informed consent form.5 

New Drug Application 

Once all phases of a study have been completed the study sponsor will then file a New Drug Application with the FDA in hopes of obtaining FDA approval. The NDA application is the vehicle through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing in the U.S.  The data gathered during the animal studies and human clinical trials of an Investigational New Drug (IND) become part of the NDA.6 

Therapeutic Areas, Indications and Medical Specialties

Sponsors are obligated to selected principal investigators that are qualified by EDUCATION, TRAINING, AND EXPERIENCE THAT QUALIFY THE INVESTIGATOR AS AN EXPERT IN THE CLINICAL INVESTIGATION OF THE DRUG FOR THE USE UNDER INVESTIGATION (refer to box 2 of the FDA Form 1572).

To learn more about clinical trials, please visit www.clinicaltrials.gov website.

ClinicalTrials.Gov - is an online registry of clinical trials that are being conducted around the world.  ClinicalTrials.gov is operated by the National Library of Medicine at the National Institutes of Health and can be accessed by anyone who has access to the internet.7 

As of May 2021, there are 378,302 studies being conducted in all 50 states and in 220 countries.  On this website established by the government, you will find information about the sponsoring company, condition, study type, phase, intervention, outcome measures for each study and more!



References

  1. NCI Dictionary of Cancer Terms. National Cancer Institute. (n.d.). https://www.cancer.gov/publications/dictionaries/cancer-terms/search/clinical%20research/?searchMode=Begins.
  2. Glossary of Common Site Terms. ClinicalTrials.gov. (n.d.). https://clinicaltrials.gov/ct2/about-studies/glossary.
  3. CFR - Code of Federal Regulations Title 21. accessdata.fda.gov. (n.d.). http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.3 
  4. Code of Federal Regulations Title 21. accessdata.fda.gov. (n.d.). https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=56.102
  5. https://www.fda.gov/media/93884/download 
  6. Center for Drug Evaluation and Research. (n.d.). New Drug Application (NDA). U.S. Food and Drug Administration. https://www.fda.gov/drugs/types-applications/new-drug-application-nda#:~:text=The%20NDA%20application%20is%20the,become%20part%20of%20the%20NDA
  7. Commissioner, O. of the. (n.d.). Glossary of Terms. U.S. Food and Drug Administration. https://www.fda.gov/patients/clinical-trials-what-patients-need-know/glossary-terms