What is Clinical Research?

Introduction to Clinical Research

Clinical research refers to studies in which people participate as patients or healthy volunteers. Different terms are used to describe clinical research, including:

Clinical Studies
Clinical Trials

Studies
Research

Trials
Protocols

Goals

Clinical research may have several goals, such as:

Developing new treatments or medications
Identifying the causes of illness
Studying trends
Evaluating ways in which genetics may be related to an illness.

The idea for a clinical research study—also known as a clinical trial—often starts in the laboratory. After researchers test new therapies or procedures in the laboratory and in animal studies, the most promising experimental treatments are moved into clinical trials, which are conducted in phases.

More information is gained about an experimental treatment, its risks, and its effectiveness during a trial.

Strict rules for clinical studies have been put in place by Health Canada and the FDA. Some studies involve promising new treatments that may directly benefit participants. Others do not directly benefit participants but may help scientists learn better ways to help people.

Confidentiality is an important part of clinical research and ensures that personal information is seen only by those authorized to have access. It also means that the personal identity and all medical information of clinical trial participants are known only to the individual patient and researchers. Results from a study will usually be presented only in terms of trends or overall findings and will not mention specific participants.

Difference Between Clincal Research & Medical Treatment

Clinical research is much different from the medical treatment you receive in a Healthcare Provider's office.

Clinical Research Versus Medical Treatment
	Clinical Research	Medical Treatment
Intent	Answers specific questions through research involving numerous research volunteers	Address the needs of individual patients
Intended Benefit	Generally designed and intended to benefit future patients	Intended to benefit the individual patient
Funding	Paid for by drug developers and government agencies	Funded by individual patients and their health plans
Timeframe	Depends on the research protocol	Requires real-time decisions
Consent	Requires written informed consent	Implied verbal consent
Assessment	Involves periodic and systematic assessment of patient data	Based on as-needed patient assessment
Protections	Protected by government agencies, institutional review boards, professional standards, informed consent, and legal standards	Guided by provential colleges, professional standards, peer review, informed consent, and legal standards
Certainty	Tests products and procedures of unproven benefit to the patient	Uses products and procedures accepted by the medical community as safe and effective - evidence-based
Access to Information	Considered confidential intellectual property	Available to the general public through product labeling
Release of Findings	Published in medical journals after clinical research ends	Individual medical records are not released to the general public

Who Should Consider Clinical Trials and Why?

Some people participate in clinical trials because none of the standard (approved) treatment options have worked or cannot tolerate certain side effects. Clinical trials provide another option when standard therapy has failed. Others participate in trials because they want to contribute to the advancement of medical knowledge.

All clinical trials have guidelines, called eligibility criteria, about who can participate. The criteria are based on such factors as age, sex, type and stage of the disease, previous treatment history, and other medical conditions. This reduces the study's variation and ensures that the researchers will answer the questions they plan to study. Therefore, not everyone who applies for a clinical trial will be accepted.

It is important to test drugs and medical products in the people they are meant to help. It is also important to conduct research on various people because different people may respond differently to treatments. Health Canada seeks to ensure that people of different ages, races, ethnic groups, and genders are included in clinical trials.

Are Clinical Trials Safe?

Health Canada works to protect participants in clinical trials and to ensure that people have reliable information before deciding whether to join a clinical trial. The Federal government has regulations and guidelines for clinical research to protect participants from unreasonable risks. Although efforts are made to control participants' risks, some may be unavoidable because we are still learning more about the study's medical treatments.

The government requires researchers to give prospective participants complete and accurate information about what will happen during the trial. Before joining a particular study, you will be given an informed consent document that describes your rights as a participant, as well as details about the study, including potential risks. Signing it indicates that you understand that the trial is research and that you may leave at any time. Informed consent is part of the process that makes sure you understand the known risks associated with the study.

What is a Placebo & How is it Related to Clinical Trials?

A placebo is a pill, liquid, or powder that has no treatment value. It is often called a sugar pill. In clinical trials, experimental drugs are often compared with placebos to evaluate the treatment’s effectiveness.

Is There a Chance I Might Get a Placebo?

In clinical trials that include placebos, neither patients nor their doctors know who is receiving the placebo and how it is treated with the experimental drug. Many cancer clinical trials and trials for other severe and life-threatening conditions do not include placebo control groups. In these cases, all participants receive the experimental drug.

Ask the trial coordinator whether there is a chance you may get a placebo rather than the experimental drug. Then, talk with your doctor about what is best for you.

What is Informed Consent?

As new medical products are being developed, no one knows how well they will work or what risks they will find. Clinical trials are used to answer questions such as:

Are new medical products safe enough to outweigh the risks related to the underlying condition?
How should the product be used? (for example, the best dose, frequency, or any special precautions necessary to avoid problems)
How effective is the medical product at relieving symptoms, treating or curing a condition?

The primary purpose of clinical trials is to “study” new medical products in people. It is essential for people who consider participation in a clinical trial to understand their role as a “subject of research” and not patient.

While research subjects may get personal treatment benefit from participating in a clinical trial, they must understand that they:

May not benefit from the clinical trial
May be exposed to unknown risks
Are entering into a study that may be very different from the standard medical practices that they currently know

To make an informed decision about whether to participate or not in a clinical trial, people need to be informed about:

What will be done to them
How the protocol (plan of research) works
What risks or discomforts they may experience
Participation is a voluntary decision on their part

This information is provided to potential participants through the informed consent process. Informed consent means that the research purpose is explained to them, including their role and how the trial will work.

A central part of the informed consent process is the informed consent document. Health Canada does not dictate the specific language required for the informed consent document but does require certain basic elements of consent to be included.

Before enrolling in a clinical trial, the following information must be given to each potential research subject:

A potential research subject must have an opportunity to:

Read the consent document
Ask questions about anything they do not understand

Usually, if one is considering participating in a clinical trial, he or she may take the consent document home to discuss with family, friend, or advocate.

An investigator should only get consent from a potential research subject if:

Enough time was given to the research subject to consider whether or not to participate
The investigator has not persuaded or influenced the potential research subject

The information must be in the language that is understandable to the research subject.

Informed consent may not include language that:

The research subject is made to ignore or appear to ignore any legal rights of the research subject
Releases or appears to release the investigator, the sponsor, the institution, or its agents from their liability for negligence

Participating in clinical trials is voluntary. You have the right not to participate or to end your participation in the clinical trial at any time. Read the informed consent document carefully. Ask questions about any information you don’t understand or find confusing.

What are the Different Types of Clinical Research?

Different types of clinical research are used depending on what the researchers are studying. Below are descriptions of some different kinds of clinical research.

Treatment Research generally involves an intervention such as medication, psychotherapy, new devices, or new approaches to surgery or radiation therapy.
Prevention Research looks for better ways to prevent disorders from developing or returning. Different kinds of prevention research may study medicines, vitamins, vaccines, minerals, or lifestyle changes.
Diagnostic Research refers to the practice of looking for better ways to identify a particular disorder or condition.
Screening Research aims to find the best ways to detect certain disorders or health conditions.
Quality of Life Research explores ways to improve comfort and the quality of life for individuals with a chronic illness.
Genetic Studies aim to improve disorders' prediction by identifying and understanding how genes and illnesses may be related. Research in this area may explore how a person’s genes make him or her more or less likely to develop a disorder. This may lead to the development of tailor-made treatments based on a patient’s genetic make-up.
Epidemiological Studies seek to identify the patterns, causes, and control of disorders in groups of people.

An important Note: Some clinical research is “outpatient,” meaning that participants do not stay overnight at the hospital. Some are “inpatient,” meaning that participants will need to stay for at least one night in the hospital or research center. Be sure to ask the researchers what their study requires.

Phases of Clinical Trials

Clinical research is used to evaluate new medications and devices. Clinical trials are designed to evaluate and test new interventions such as psychotherapy or medications. Clinical trials are often conducted in four phases. The trials at each phase have a different purpose and help scientists answer different questions.

Phase I Trials

Researchers test an experimental drug or treatment in a small group of people for the first time. The researchers evaluate the treatment’s safety, determine a safe dosage range, and identify side effects.

Phase II Trials

The experimental drug or treatment is given to a larger group of people to see if it is effective and further evaluate its safety.

Phase III Trials

The experimental study drug or treatment is given to large groups of people. Researchers confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information to allow the experimental drug or treatment to be used safely.

Phase IV Trials

Post-marketing studies, which are conducted after a treatment is approved for use by the Health Canada, provide additional information including the treatment or drug’s risks, benefits, and best use.

Examples of Other Kinds of Clinical Research

Many people believe that all clinical research involves testing of new medications or devices. This is not true, however. Some studies do not involve testing medications, and a person’s regular medications may not need to be changed. Healthy volunteers are also needed so that researchers can compare their results to the results of people with the illness being studied. Some examples of other kinds of research include the following:

A long-term study that involves psychological tests or brain scans
A genetic study that involves blood tests but no changes in medication
A study of family history that involves talking to family members to learn about people’s medical needs and history

What Patients Need to Know About Research Ethics Boards

Health Canada has authority over clinical trials for drug, biologic, and medical device products regulated by the agency. This authority includes studies funded by the U.S. Department of Health and Human Services (with joint oversight by the FDA and the Office for Human Research Protections) and studies solely funded by industry or private parties.

Clinical trial procedures are reviewed by research ethics boards (REBs). These boards are composed of at least five members that include scientists, doctors, and laypeople. They review and approve clinical trials taking place within their jurisdiction before the trials can begin.

The purpose of an REB review is to ensure that appropriate steps are taken to protect participants' rights and welfare as research subjects. If the risks to participants are too significant, the REB will not approve the research, or it will specify changes that must be made before the research can be done.

As part of their review, REBs consider participant inclusion and exclusion requirements to ensure that appropriate people have been identified as eligible for the trial. They often look at how and where recruitment for clinical trials will occur.

The REB also reviews how much money participants receive and what those payments are for. Paying research subjects to participate in clinical trials is common and is generally considered an acceptable practice. The REB reviews any payments for participation to ensure they are not coercive and do not have undue influence upon someone’s decision to participate.

In contrast to payment for participation, Health Canada does not consider reimbursement for travel expenses to and from the clinical trial site and associated costs such as airfare, parking, and lodging to raise undue influence issues. Payment for participation in research should be just and fair. The REB should review both the amount of payment and the method and timing of the payment to ensure they are appropriate and follow the laws.

REBs review the adequacy of the informed consent document to ensure that it includes all the elements required by law. It is at an appropriate reading level and understandable to study participants.

To help protect the rights and welfare of volunteers and verify the quality and integrity of data submitted for review, Health Canada performs inspections of clinical trial study sites and anyone involved in the research.

Many groups play important roles in looking out for the safety of research subjects. These groups include Health Canada, other government agencies, and research ethics boards. There is also monitoring of studies by industry or private sponsors and oversight and reporting by investigators and their staff.

The Clinical Research Process

Step 1: Discovery and Development

Typically, researchers discover new drugs through:

New insights into a disease process that allow researchers to design a product to stop or reverse the effects of the disease
Many tests of molecular compounds to find possible beneficial effects against any of a large number of diseases
Existing treatments that have unanticipated effects
New technologies, such as those that provide new ways to target medical products to specific sites within the body or to manipulate genetic material

At this stage in the process, thousands of compounds may be potential candidates for development as a medical treatment. However, after early testing, only a small number of compounds look promising and call for further study.

Development

Once researchers identify a promising compound for development, they conduct experiments to gather information on:

How it is absorbed, distributed, metabolized, and excreted
Its potential benefits and mechanisms of action
The best dosage
The best way to give the drug (such as by mouth or injection)
Side effects or adverse events that can often be referred to as toxicity
How it affects different groups of people (such as by gender, race, or ethnicity) differently
How it interacts with other drugs and treatments
Its effectiveness as compared with similar drugs

Step 2: Pre-Clinical Research

Before testing a drug in people, researchers must find out whether it can cause serious harm, also called toxicity. The two types of preclinical research are:

In vitro
In vivo

FDA requires researchers to use good laboratory practices (GLP), defined in medical product development regulations, for preclinical laboratory studies. The GLP regulations are found in 21 CFR Part 58.1: Good Laboratory Practice for Nonclinical Laboratory Studies. These regulations set the minimum basic requirements for:

Study conduct
Personnel
Facilities
Equipment
Written protocols
Operating procedures
Study reports
System of quality assurance oversight for each study to help assure the safety of FDA-regulated product

Usually, preclinical studies are not very large. However, these studies must provide detailed information on dosing and toxicity levels. After preclinical testing, researchers review their findings and decide whether the drug should be tested in people.

Step 3: Clinical Research

Designing Clinical Trials

Researchers design clinical trials to answer specific research questions related to a medical product. These trials follow a specific study plan, called a protocol, the researcher or manufacturer develops that. Before a clinical trial begins, researchers review prior information about the drug to develop research questions and objectives. Then, they decide:

Who qualifies to participate (selection criteria)
How many people will be part of the study
How long the study will last
Whether there will be a control group and other ways to limit research bias
How the drug will be given to patients, and at what dosage
What assessments will be conducted, when, and what data will be collected
How the data will be reviewed and analyzed

Clinical trials follow a typical series from early, small-scale, Phase 1 studies to late-stage, large scale, Phase 3 studies.

The Investigational New Drug Process

Drug developers, or sponsors, must submit an Investigational New Drug (IND) application to FDA before beginning clinical research.

In the IND application, developers must include:

Animal study data and toxicity (side effects that cause great harm) data
Manufacturing information
Clinical protocols (study plans) for studies to be conducted
Data from any prior human research
Information about the investigator

Clinical Research Phase Studies

Phase 1

Study Participants: 20 to 100 healthy volunteers or people with the disease/condition.
Length of Study: Several months
Purpose: Safety and dosage
Approximately 70% of drugs move to the next phase

Phase 2

Study Participants: Up to several hundred people with the disease/condition.
Length of Study: Several months to 2 years
Purpose: Efficacy and side effects
Approximately 33% of drugs move to the next phase

Phase 3

Study Participants: 300 to 3,000 volunteers who have the disease or condition
Length of Study: 1 to 4 years
Purpose: Efficacy and monitoring of adverse reactions
Approximately 25-30% of drugs move to the next phase

Phase 4

Study Participants: Several thousand volunteers who have the disease/condition
Purpose: Safety and efficacy

Learn more about Clinical Trials.

The Investigational New Drug Process

Drug developers, or sponsors, must submit an Investigational New Drug (IND) application to FDA before beginning clinical research.

In the IND application, developers must include:

Animal study data and toxicity (side effects that cause great harm) data
Manufacturing information
Clinical protocols (study plans) for studies to be conducted
Data from any prior human research
Information about the investigator

Asking for FDA Assistance

Drug developers are free to ask for help from FDA at any point in the drug development process, including:

Pre-IND application, to review FDA guidance documents and get answers to questions that may help enhance their research
After Phase 2, to obtain guidance on the design of large Phase 3 studies
Any time during the process, to obtain an assessment of the IND application

Even though FDA offers extensive technical assistance, drug developers are not required to take FDA’s suggestions. As long as clinical trials are thoughtfully designed, reflect what developers know about a product, safeguard participants, and otherwise meet Federal standards, FDA allows wide latitude in clinical trial design.

FDA IND Review Team

The review team consists of a group of specialists in different scientific fields. Each member has different responsibilities.

Project Manager: Coordinates the team’s activities throughout the review process and is the primary contact for the sponsor
Medical Officer: Reviews all clinical study information and data before, during, and after the trial is complete
Statistician: Interprets clinical trial designs and data and works closely with the medical officer to evaluate protocols and safety and efficacy data.
Pharmacologist: Reviews preclinical studies
Pharmacokineticist: Focuses on the drug’s absorption, distribution, metabolism, and excretion processes. Interprets blood-level data at different time intervals from clinical trials as a way to assess drug dosages and administration schedules
Chemist: Evaluates a drug’s chemical compounds. Analyzes how a drug was made and its stability, quality control, continuity, the presence of impurities, etc
Microbiologist: Reviews the data submitted, if the product is an antimicrobial product, to assess response across different classes of microbes

Approval

The FDA review team has 30 days to review the original IND submission. The process protects volunteers who participate in clinical trials from unreasonable and significant risk. FDA responds to IND applications in one of two ways:

Approval to begin clinical trials
Clinical hold to delay or stop the investigation. FDA can place a clinical hold for specific reasons, including:
Participants are exposed to an unreasonable or significant risk
Investigators are not qualified
Materials for the volunteer participants are misleading
The IND application does not include enough information about the trial’s risks

A clinical hold is rare; instead, the FDA often provides comments intended to improve a clinical trial quality. In most cases, if the FDA is satisfied that the trial meets Federal standards, the applicant is allowed to proceed with the proposed study.

The developer is responsible for informing the review team about new protocols and serious side effects seen during the trial. This information ensures that the team can monitor the trials carefully for signs of any problems. After the trial ends, researchers must submit study reports.

This process continues until the developer decides to end clinical trials or files a marketing application. Before filing a marketing application, a developer must have adequate data from two large, controlled clinical trials.

Step 4: FDA Drug Review / Health Canada Review

Suppose a drug developer has evidence from its early tests and preclinical and clinical research that a drug is safe and effective for its intended use. In that case, the company can apply to market the drug. The FDA review team thoroughly examines all submitted data on the drug and decides to approve or not approve it.

Find out how the FDA is Speeding Up the Approval Process.

New Drug Application

A New Drug Application (NDA) tells the full story of a drug. Its purpose is to demonstrate that a drug is safe and effective for its intended use in the population studied.

A drug developer must include everything about a drug—from preclinical data to Phase 3 trial data—in an NDA. Developers must include reports on all studies, data, and analyses. Along with clinical results, developers must include:

Proposed labeling
Safety updates
Drug abuse information
Patent information
Any data from studies that may have been conducted outside the United States
Institutional review board compliance information
Directions for use

FDA Review

Once the FDA receives an NDA, the review team decides if it is complete. If it is not complete, the review team can refuse to file the NDA. If it is complete, the review team has 6 to 10 months to decide whether to approve the drug. The process includes the following:

Each member of the review team conducts a full review of his or her section of the application. For example, the medical officer and the statistician review clinical data, while a pharmacologist reviews the data from animal studies. Within each technical discipline represented on the team, there is also a supervisory review.
FDA inspectors travel to clinical study sites to conduct a routine inspection. The agency looks for evidence of fabrication, manipulation, or withholding of data.
The project manager assembles all individual reviews and other documents, such as the inspection report, into an “action package.” This document becomes the record for FDA review. The review team issues a recommendation, and a senior FDA official makes a decision.

FDA Approval

In cases where FDA determines that a drug is safe and effective for its intended use, it is then necessary to work with the applicant to develop and refine prescribing information. This is referred to as “labeling.” Labeling accurately and objectively describes the basis for approval and how best to use the drug.

Often, though, remaining issues need to be resolved before the drug can be approved for marketing. Sometimes FDA requires the developer to address questions based on existing data. In other cases, the FDA requires additional studies. At this point, the developer can decide whether or not to continue further development. If a developer disagrees with an FDA decision, there are mechanisms for a formal appeal.

FDA Advisory Committees

Often, the NDA contains sufficient data for the FDA to determine the safety and effectiveness. Sometimes, though, questions arise that require additional consideration. In these cases, FDA may organize a meeting of one of its Advisory Committees to get independent, expert advice and permit the public to make comments. These Advisory Committees include a patient representative that provides input from the patient perspective. Learn more about FDA Advisory Committees.

Step 5: Health Canada Post-Market Drug Safety Monitoring

Even though clinical trials provide important information on a drug’s efficacy and safety, it is impossible to have complete information about a drug's safety at the time of approval. Despite the rigorous steps in the process of drug development, limitations exist. Therefore, the accurate picture of a product’s safety evolves over the months and even years that make up a product’s lifetime in the marketplace. FDA reviews reports of problems with prescription and over-the-counter drugs and can decide to add cautions to the dosage or usage information and other measures for more serious issues.

On this page, you will find information on:

Supplemental Applications

Developers must file a supplemental application if they wish to make any significant changes from the original NDA. Generally, the FDA must approve any formulation, labeling, or dosage strength changes before they can be made.

INDs for Marketed Drugs

If sponsors want to further develop an approved drug for a new use, dosage strength, new form, or different form (such as an injectable or oral liquid, as opposed to tablet form), or if they want to conduct other clinical research or a postmarket safety study, they will do so under an IND.

Manufacturer Inspections

FDA officials conduct routine inspections of drug manufacturing facilities across the United States and abroad if approved products are manufactured overseas. Manufacturers may be informed of inspections in advance, or the inspections may be unannounced. Inspections may be routine or caused by a particular problem or concern. The purpose of these inspections is to make sure that developers are following good manufacturer practice. FDA can shut down a facility if minimum standards are not met.

Drug Advertising

FDA regulates prescription drug advertisements and promotional labeling. By law, a developer is prohibited from advertising unapproved uses of their product.

All advertisements, such as product claims or reminder ads, cannot be false or misleading. They must contain truthful information about a drug’s effectiveness, side effects, and prescribing information. These advertisements can be found in medical journals, newspapers, magazines, and on the Internet, television, or radio.

Promotional labeling differs from drug advertisements in the way it is distributed. Pharmaceutical companies give out brochures or other promotional materials to physicians or consumers. The drug’s prescribing information must accompany promotional labeling. Learn more at Prescription Drug Advertising.

Generic Drugs

New drugs are patent protected when they are approved for marketing. This means that only the sponsor has the right to market the drug exclusively. Once the patent expires, other drug manufacturers can develop the drug, known as a generic version of the drug. Generic drugs are comparable to brand name drugs and must have the same:

Because generic drugs are comparable to drugs already on the market, generic drug manufacturers do not have to conduct clinical trials to demonstrate that their product is safe and effective. Instead, they conduct bio-equivalence studies and file an Abbreviated New Drug Application. Learn more at .

Reporting Problems

FDA has several programs that allow manufacturers, health professionals, and consumers to report problems associated with approved drugs.

MedWatch is a gateway for reporting problems with medical products (drugs and devices) and learning about new safety information. You can subscribe to regular MedWatch safety alerts.
Medical Product Safety Network (MedSun) monitors the safety and effectiveness of medical devices. FDA recruits 350 healthcare providers throughout the United States to report any medical device problems that result in serious injury or death. Each month, FDA publishes the MedSun newsletter. The newsletter gives consumers important information about medical device safety.

Active Surveillance

Under the Sentinel Initiative, the FDA is developing a new national system to spot possible safety issues more quickly. The system will use very large existing electronic health databases—like electronic health records systems, administrative and insurance claims databases, and registries—to keep an eye on approved medical products' safety in real-time. This tool will add to, but not replace, FDA's existing postmarket safety assessment tools. Learn more about the Sentinel Initiative and its major activities.

Additional Resources

If you are seeking additional information about clinical research, we recommend the following websites for anyone considering clinical trial participation.