Clinical trials are sets of tests in medical research and drug development that generate safety and efficacy data (or more specifically, information about adverse drug reactions
and adverse effects of other treatments) for health interventions
(e.g., drugs, diagnostics, devices, therapy protocols). They are
conducted only after satisfactory information has been gathered on the
quality of the nonclinical safety, and health authority/ethics committee approval is granted in the country where approval of the drug or device is sought. Previously, many emerging countries
did not require local trials for product approvals. Now, though
emerging countries still accept data from U.S./Europe, they also require
some local trials.
Depending on the type of product and the stage of its development, investigators initially enroll volunteers and/or patients into small pilot studies, and subsequently conduct larger scale studies in patients that often compare the new product with others already approved for the affliction of interest. As positive safety and efficacy data are gathered, the number of patients is typically increased. Clinical trials can vary in size, and can involve a single research entity in one country or many such entities in multiple countries.
A full series of trials may incur sizable costs, and the burden of paying for all the necessary people and services is usually borne by the sponsor, which may be a governmental organization or a pharmaceutical, biotechnology or medical device company. When the diversity of required support roles exceeds the resources of the sponsor, a clinical trial is managed by an outsourced partner, such as a contract research organization or a clinical trials unit in the academic sector.
OVERVIEW
Clinical trials often involve patients with specific health conditions who then benefit from receiving otherwise unavailable treatments. In early phases, participants are healthy volunteers who receive financial incentives for their inconvenience. During dosing periods, study subjects typically remain on site at the unit for durations of one to 40 nights, and occasionally longer, although this is not always the case.
Usually, one or more pilot experiments are conducted to gain insights for design of the clinical trial to follow. In medical jargon, effectiveness is how well a treatment works in practice and efficacy is how well it works in a clinical trial. In the US, the elderly comprise only 14% of the population, but they consume over one-third of drugs.[1] Despite this, they are often excluded from trials because their more frequent health issues and drug use produce unreliable data. Women, children, and people with unrelated medical conditions are also frequently excluded.[2]
In coordination with a panel of expert investigators (usually physicians well known for their publications and clinical experience), the sponsor decides what to compare the new agent with (one or more existing treatments or a placebo), and what kind of patients might benefit from the medication or device. If the sponsor cannot obtain enough patients with this specific disease or condition at one location, then investigators at other locations who can obtain the same kind of patients to receive the treatment would be recruited into the study.
During the clinical trial, the investigators: recruit patients with the predetermined characteristics, administer the treatment(s), and collect data on the patients' health for a defined time period. These patients are volunteers and they are not paid for participating in clinical trials. These data include measurements like vital signs, concentration of the study drug in the blood, and whether the patient's health improves or not. The researchers send the data to the trial sponsor, who then analyzes the pooled data using statistical tests.
Some examples of what a clinical trial may be designed to do:
Except for very small trials limited to a single location, the clinical trial design and objectives are written into a document called a clinical trial protocol. The protocol is the 'operating manual' for the clinical trial and ensures the researchers in different locations all perform the trial in the same way on patients with the same characteristics. (This uniformity is designed to allow the data to be pooled.) A protocol is always used in multicenter trials.
Because the clinical trial is designed to test hypotheses and rigorously monitor and assess what happens, clinical trials can be seen as the application of the scientific method, and specifically the experimental step, to understanding human or animal biology.
The most commonly performed clinical trials evaluate new drugs, medical devices (like a new catheter), biologics, psychological therapies, or other interventions. Clinical trials may be required before the national regulatory authority[3] approves marketing of the drug or device, or a new dose of the drug, for use on patients.
HISTORY
The history of clinical trials before 1750 is brief.[4][5]
The concepts behind clinical trials, however, are ancient. The Book of Daniel
chapter 1, verses 12 through 15, for instance, describes a planned
experiment with both baseline and follow-up observations of two groups
who either partook of, or did not partake of, "the King's meat" over a
trial period of ten days. Persian physician and philosopher, Avicenna, gave such inquiries a more formal structure.[6] In The Canon of Medicine in 1025 CE, he laid down rules for the experimental use and testing of drugs and wrote a precise guide for practical experimentation in the process of discovering and proving the effectiveness of medical drugs and substances.[7] He laid out the following rules and principles for testing the effectiveness of new drugs and medications:[8][9][verification needed]
Frederick Akbar Mahomed (d. 1884), who worked at Guy's Hospital in London,[11] made substantial contributions to the process of clinical trials during his detailed clinical studies, where "he separated chronic nephritis with secondary hypertension from what we now term essential hypertension." He also founded "the Collective Investigation Record for the British Medical Association; this organization collected data from physicians practicing outside the hospital setting and was the precursor of modern collaborative clinical trials and t123."[12]
Depending on the type of product and the stage of its development, investigators initially enroll volunteers and/or patients into small pilot studies, and subsequently conduct larger scale studies in patients that often compare the new product with others already approved for the affliction of interest. As positive safety and efficacy data are gathered, the number of patients is typically increased. Clinical trials can vary in size, and can involve a single research entity in one country or many such entities in multiple countries.
A full series of trials may incur sizable costs, and the burden of paying for all the necessary people and services is usually borne by the sponsor, which may be a governmental organization or a pharmaceutical, biotechnology or medical device company. When the diversity of required support roles exceeds the resources of the sponsor, a clinical trial is managed by an outsourced partner, such as a contract research organization or a clinical trials unit in the academic sector.
OVERVIEW
Clinical trials often involve patients with specific health conditions who then benefit from receiving otherwise unavailable treatments. In early phases, participants are healthy volunteers who receive financial incentives for their inconvenience. During dosing periods, study subjects typically remain on site at the unit for durations of one to 40 nights, and occasionally longer, although this is not always the case.
Usually, one or more pilot experiments are conducted to gain insights for design of the clinical trial to follow. In medical jargon, effectiveness is how well a treatment works in practice and efficacy is how well it works in a clinical trial. In the US, the elderly comprise only 14% of the population, but they consume over one-third of drugs.[1] Despite this, they are often excluded from trials because their more frequent health issues and drug use produce unreliable data. Women, children, and people with unrelated medical conditions are also frequently excluded.[2]
In coordination with a panel of expert investigators (usually physicians well known for their publications and clinical experience), the sponsor decides what to compare the new agent with (one or more existing treatments or a placebo), and what kind of patients might benefit from the medication or device. If the sponsor cannot obtain enough patients with this specific disease or condition at one location, then investigators at other locations who can obtain the same kind of patients to receive the treatment would be recruited into the study.
During the clinical trial, the investigators: recruit patients with the predetermined characteristics, administer the treatment(s), and collect data on the patients' health for a defined time period. These patients are volunteers and they are not paid for participating in clinical trials. These data include measurements like vital signs, concentration of the study drug in the blood, and whether the patient's health improves or not. The researchers send the data to the trial sponsor, who then analyzes the pooled data using statistical tests.
Some examples of what a clinical trial may be designed to do:
- Assess the safety and effectiveness of a new medication or device on a specific kind of patient (e.g., patients who have been diagnosed with Alzheimer's disease)
- Assess the safety and effectiveness of a different dose of a medication than is commonly used (e.g., 10-mg dose instead of 5-mg dose)
- Assess the safety and effectiveness of an already marketed medication or device for a new indication, i.e. a disease for which the drug is not specifically approved
- Assess whether the new medication or device is more effective for the patient's condition than the already used, standard medication or device ("the gold standard" or "standard therapy")
- Compare the effectiveness in patients with a specific disease of two or more already approved or common interventions for that disease (e.g., device A vs. device B, therapy A vs. therapy B)
Except for very small trials limited to a single location, the clinical trial design and objectives are written into a document called a clinical trial protocol. The protocol is the 'operating manual' for the clinical trial and ensures the researchers in different locations all perform the trial in the same way on patients with the same characteristics. (This uniformity is designed to allow the data to be pooled.) A protocol is always used in multicenter trials.
Because the clinical trial is designed to test hypotheses and rigorously monitor and assess what happens, clinical trials can be seen as the application of the scientific method, and specifically the experimental step, to understanding human or animal biology.
The most commonly performed clinical trials evaluate new drugs, medical devices (like a new catheter), biologics, psychological therapies, or other interventions. Clinical trials may be required before the national regulatory authority[3] approves marketing of the drug or device, or a new dose of the drug, for use on patients.
HISTORY
The history of clinical trials before 1750 is brief.[4][5]
- The drug must be free from any extraneous accidental quality.
- It must be used on a simple, not a composite, disease.
- The drug must be tested with two contrary types of diseases, because sometimes a drug cures one disease by its essential qualities and another by its accidental ones.
- The quality of the drug must correspond to the strength of the disease. For example, there are some drugs whose heat is less than the coldness of certain diseases, so that they would have no effect on them.
- The time of action must be observed, so that essence and accident are not confused.
- The effect of the drug must be seen to occur constantly or in many cases, for if this did not happen, it was an accidental effect.
- The experimentation must be done with the human body, for testing a drug on a lion or a horse might not prove anything about its effect on man.
Frederick Akbar Mahomed (d. 1884), who worked at Guy's Hospital in London,[11] made substantial contributions to the process of clinical trials during his detailed clinical studies, where "he separated chronic nephritis with secondary hypertension from what we now term essential hypertension." He also founded "the Collective Investigation Record for the British Medical Association; this organization collected data from physicians practicing outside the hospital setting and was the precursor of modern collaborative clinical trials and t123."[12]
