The United States has always been and remains to be the leading place for the conduct of clinical trials. According to Clinicaltrials.gov, the largest clinical trials registry, 32% of registered clinical trials were conducted in the U.S. as of May 2022 (1). Factors such as the availability of qualified healthcare professionals, high-quality infrastructure and facilities, cutting-edge research, an efficient regulatory system, and a high standard of ethics and participant protection make the U.S. the leading country for clinical trials. Clinical trials follow extensive preclinical research to test the safety and efficacy of a new drug, medical device, or biological in humans. They are usually divided into three phases: phases I, II, and III which are designed to ascertain safety, pharmacokinetics, efficacy, dosage, and adverse events. Figure 1 shows the typical route from discovery and preclinical studies to the post-marketing phase (phase IV).Clinical trials represent the longest and most expensive step in bringing drugs to the market and have the highest attrition rate, only 10% of drugs that enter phase I trials are granted marketing approval. Therefore, clinical trials should be conducted by experts that are well-versed with all the regulations and guidelines in a particular region to boost the chances of drug approval. The United States Food and Drug Administration (US FDA) is the regulatory body that approves and oversees the conduct of clinical trials for drugs, medical devices, and biologicals that are intended to be marketed in the U.S and is touted to have the most stringent standards for drug approval. The primary role of the FDA is to protect public health by ensuring that medicinal products and devices are safe and efficacious. Therefore, it is necessary for sponsors/investigators or contract research organizations (CRO) that are conducting clinical trials to be familiar with regulations and guidances that govern the conduct of clinical trials.Conducting a clinical trial in the United States requires a deep understanding of the regulations and guidelines set by the FDA. It is important to know what is needed for a successful clinical trial, from selecting an appropriate study site to obtaining informed consent from participants. Additionally, it is essential to understand the requirements for data collection and analysis, as well as how to develop an effective protocol. Clinical trial services in USA can provide guidance on all of these aspects and more, helping you ensure that your clinical trial meets all necessary standards

1. Planning Clinical Trial in USA? Here is what you
should know
Table of Contents
​ 1)What you need to know to conduct a Clinical Trial in the United
States
​ 1. Regulations
​ 2. Good Clinical Practice (GCP) Guidelines
​ 3. Regulatory pathways
​ 4. Ethical considerations
​ 5. Site requirements
​ 2)References

2. The United States has always been and remains to be the leading place
for the conduct of clinical trials. According to Clinicaltrials.gov, the largest
clinical trials registry, 32% of registered clinical trials were conducted in
the U.S. as of May 2022 (1). Factors such as the availability of qualified
healthcare professionals, high-quality infrastructure and facilities,
cutting-edge research, an efficient regulatory system, and a high
standard of ethics and participant protection make the U.S. the leading
country for clinical trials.
Clinical trials follow extensive preclinical research to test the safety and
efficacy of a new drug, medical device, or biological in humans. They are
usually divided into three phases: phases I, II, and III which are designed
to ascertain safety, pharmacokinetics, efficacy, dosage, and adverse
events. Figure 1 shows the typical route from discovery and preclinical
studies to the post-marketing phase (phase IV).
Drug approval pathway. IND: Investigational New Drug, IDE: Investigational Device Exemption, NDA:
New Drug Application, BLA: Biologics License Application
Figure 1. Drug approval pathway. IND: Investigational New Drug, IDE:
Investigational Device Exemption, NDA: New Drug Application, BLA:
Biologics License Application
Clinical trials represent the longest and most expensive step in bringing
drugs to the market and have the highest attrition rate, only 10% of drugs
that enter phase I trials are granted marketing approval. Therefore,
clinical trials should be conducted by experts that are

3. well-versed with all the regulations and guidelines in a particular region to
boost the chances of drug approval.
The United States Food and Drug Administration (US FDA) is the
regulatory body that approves and oversees the conduct of clinical trials
for drugs, medical devices, and biologicals that are intended to be
marketed in the U.S and is touted to have the most stringent standards
for drug approval. The primary role of the FDA is to protect public health
by ensuring that medicinal products and devices are safe and efficacious.
Therefore, it is necessary for sponsors/investigators or contract research
organizations (CRO) that are conducting clinical trials to be familiar with
regulations and guidances that govern the conduct of clinical trials.
What you need to know to conduct a Clinical Trial in
the United States
Conducting a clinical trial in the United States requires a deep understanding of the
regulations and guidelines set by the FDA. It is important to know what is needed for a
successful clinical trial, from selecting an appropriate study site to obtaining informed
consent from participants. Additionally, it is essential to understand the requirements for data
collection and analysis, as well as how to develop an effective protocol. Clinical trial services
in USA can provide guidance on all of these aspects and more, helping you ensure that your
clinical trial meets all necessary standards.

4. Clinical Trial in USA
1. Regulations
Sponsors, investigators, or CROs planning to carry out clinical trials in
theU.S. need to comply with federal regulations that are listed in the Part
21 Code of Federal Regulations (CFR). Details regarding these
regulations are available on the official FDA website
(https://www.fda.gov(2)). The applicable CFR regulations that are
noteworthy include:
● 21 CFR Part 50: Protection of Human Subjects which related to
informed consent from human subjects or legally authorized
representatives. This part describes the elements of informed
consent and exceptions.
● 21 CFR Part 54: Financial Disclosure by Clinical Investigators
which details disclosure of financial agreements between the
sponsor and clinical investigator in cases of the financial interest of
the investigator based on royalties or patents.

5. ● 21 CFR Part 56: Institutional Review Boards provides details on
the standards for the composition, operation, and responsibility of
an IRB.
● 21 CFR 312: Investigational New Drug (IND) Application which
includes procedures, requirements, and submission of INDs.
● 21 CFR 812: Investigational Device Exemptions is related to
clinical investigations of devices.
● 21 CFR Part 814: Premarket Approval (PMA) of Medical Devices
outlines the review process for approval or disapproval of PMAs
2. Good Clinical Practice (GCP) Guidelines
A thorough understanding of and compliance with Good Clinical Practice
(GCP) guidelines by sponsors and investigators is essential in protecting
the rights, confidentiality, and well-being of human subjects along with
ensuring reliable and accurate clinical data. The U.S. uses the GCP
guideline developed by the International Council for Harmonisation of
Technical Requirements for Pharmaceuticals for Human Use (ICH). The
ICH-GCP guideline includes the following information that should be
followed by various parties involved in a clinical trial and the
documentation required (2):
● Institutional Review Board (IRB)/Independent Ethics
Committee (IEC): Responsibilities, composition, function,
procedures, and records
● Investigator: Qualification and training, adequate staff availability
and facilities, contracts with CROs, medical care of trial subjects,
communication with IRB/IEC, compliance with the protocol,
reporting of any protocol deviations, handling the investigational
product (IP), obtaining informed consent, maintenance of source
documentation, safety reporting
● Sponsor: Development of a quality management system using a
risk-based approach, implementation and maintenance of quality
control and quality assurance systems, oversight of any trial
activities conducted by CROs, trial design, management, data
handling, record keeping, investigator selection, financing, IRB/IEC
approval confirmation, adequate nonclinical data to support the IP,
suitable manufacturing and packaging conditions for the IP, supply,
and distribution of the IP, ongoing safety evaluation, and adverse
drug reaction reporting, suitable monitoring, and audit plans

6. ● Clinical trial protocol and protocol amendments: Trial design,
objectives, selection and treatment of subjects, ethics, data
handling, and record keeping, statistics, assessment of safety and
efficacy, financing, and insurance
● Investigator’s brochure contents and format
● Essential documents before, during, and after the trial
3. Regulatory pathways
Understanding the regulatory pathways for the approval of drugs, medical
devices, and biologicals is important to expedite the approval process.
The utilization of abbreviated routes for approval can benefit the sponsor
by saving considerable time and money. The requirements vary for each
pathway and need to be understood. The common pathways for approval
that any sponsor should be familiar with are:
● New drugs: 505(b)(1) pathway for New Drug Application (NDA)
which includes extensive clinical studies (phase I-III)
● Generic drugs: Abbreviated new drug application (ANDA) that
emphasizes the importance of bioequivalence studies
● Repurposed drugs: 505(b)(2) pathway for repurposed or
repositioned drugs which precludes the need for extensive
preclinical and clinical studies. This pathway for regulatory
approval focuses instead on the compilation of existing information
from FDA literature or labeling, and the conduct of gap analysis
and bridging studies
● Medical devices: Premarket notification (PMN) or 501(k) process
for Class II devices that shows substantial equivalence to
predicate devices. Premarket approval (PMA) and Investigational
device exemption (IDE) for Class III medical devices
● In vitro diagnostic (IVD) devices: 510(k) or premarket approval
(PMA) process depending on device classification
● Biologics: Traditional or full biologics license application (BLA)
351(a) for innovator biologicals and biosimilar BLA section 351(k)
for biosimilar biologicals
4. Ethical considerations

7. Although ethics are a part of CFR and GCP guidelines, it is necessary to
emphasize this aspect as the protection of human subjects is of utmost
importance during a clinical trial. The three main principles for ethical
research that are part of the ICH-GCP guidelines and which in turn are
drawn from the Belmont report are respect for persons (informed
consent), beneficence (benefits should outweigh risks), and justice
(equitable selection and treatment of human subjects). It is imperative for
the sponsor/investigator to obtain ethical approval from the IRB/IEC prior
to commencing clinical research as well as voluntary consent from
subjects or their legally authorized representatives (LARs). In addition to
federal regulations, sponsors or CROs must be aware of state legislation
such as protection of human subjects, confidentiality statements, rules
related to consent from minors and prisoners, codes related to parenteral
consent, etc. that may be required for conducting clinical trials in some
states in the U.S.
5. Site requirements
Availability of resources at clinical trial sites, adequate drug storage
facilities, and trained personnel are important when conducting a clinical
trial. It is essential to have a clinical trial coordinator (CRC) at each trial
site who is responsible for the day-to-day activities of the trial. Since
documentation is a critical factor for trials and regulatory submissions, the
site must have a system to store and archive all patient data records in a
secure manner. Any equipment or instruments that are required for
sample collection and processing must be available at the site in addition
to suitable storage facilities such as cold storage to avoid sample
degradation. Sites should also be chosen based on their proximity to
hospitals or nursing homes to allow for the recruitment of a sufficient
number of subjects for the trial to meet enrolment targets.
Successful completion of a clinical trial in the USA requires the sponsor
or CRO to have a strong knowledge of the requirements for clinical trials.
This will help streamline the trial and regulatory approval process.
References

8. ● Trends, Charts, and Maps – ClinicalTrials.gov
● E6(R2) Good Clinical Practice: Integrated Addendum to ICH
E6(R1) Guidance for Industry, March 2018