Clinical trials are often performed to identify the effect of a drug, its side effects, its treatment cure effectiveness, and dosage limits. Often drugs are verified for all these in all phases. Phase 1 is for basic test to determine the approximate range for the dosage of drug and to find the side effects. Phase 2 involves in proper estimation of the dosage and the side effects with over bigger population than the phase 1. Phase 3 involves in exact estimation of the dosage, side effects the drug causes and the treatment effectiveness in comparison with the methods that are already available in current standard. After all these tests are performed, still the drug may cause some side effect over a very long period of time. Such things are to be considered in phase 4.

Phase 4 Trial

Phase 1 trials evaluates completely on the dosage of the drug and the side effects. It does not actually calculate the exact amount of dosage that can be allowed on certain individuals. In Phase 2 trials, these things are taken into account, the dosage amount is set, and the side effects are analyzed for predetermined dosage level on a relatively larger test subjects. However, it is in the phase 3 trial, that the exact working of the drug and the comparative working of treatment available on market currently is analyzed. If the treatment found is as good as or much better than the one available on the market, the drug can be used for phase 3 trials. Phase 3 trials include test with over a large group of test subjects, divided into two. One group gets the new treatment, while the other gets the standard treatment. With the effectiveness in the drug, they can be compared and data are analyzed. Often, in market the phase 3 trials can be ongoing. Such on going trials are considered as phase 4. Phase 4 includes the post surveillance to the market trials.

With only the three phase trials (phase 1, 2 and 3), it is often enough to determine the treatment cure efficacy. However, sometimes, there could be patients who are not test subjects. In that case, the effects of the drugs on them are not known. Example, pregnant women are not likely to be the test subjects. Therefore, the drug effect on them is unknown or uncertain. So, the company or the sponsors take a special technical care in support of the drug after it is sold in the market. The regulatory authorities may themselves take steps to undertake the phase 4 trials. The companies also do phase 4 trials to identify newer potential market for the drug often. The safety surveillance of the phase 4 trial are designed so as to determine and identify any long or rare side effects due to the drug over a very large amount of time, which was not possible to be analyzed through the three phase trials. Any harmful effect identified or reported by the drug may require the drug never be sold on the market or sold under some regulations and restricted use.

Aims of phase 4 Trials

Phase 4 trials aims at finding out
1.    How well the drug actually works with wide population rather than smaller amount of test subjects
2.    The side effects that could be caused by used by various patients at various conditions, environment and more about the side effects.
3.    What is the long-term risk associated with the drug?
4.    What are the benefits with the drug, rather than the ones used currently?

Companies run phase 4 trials to know how efficient the drugs the doctors prescribe are from their product. These trials are performed once after the drug is sold in market. Phase 4 trials can also be used to identify the sale pattern of the drug and identify the market scope of the drug.

Conclusion:

Phase 4 is nothing but technical supports offered by the company willing to accept any reports and reconsider their product. Companies often use phase 4 studies to identify newer market and analyze the market scope of the product in comparison with the existing treatment.

Clinical trials are performed to test the effectiveness of the drug on human subjects and to find the acceptable dosage of usage of the drug. In addition, clinical trials are performed to evaluate the side effects caused by the drug. They also lead to solutions on how to manage them. Clinical trials also determine the quality of the drug from the manufacturers and its effectiveness in curing the disease or symptom under consideration. There could be better ways other than the one under study, all such possibilities are analyzed, and the data are managed well for the future studies. With phase 1 and phase 2 trials, the drug has passed the preliminary tests in identifying the side effects and dosage to be given to a patient. Not only with these, it has passed on to the phase 3 trial because it is as good as the drugs already available or much better treatment than the ones available for cure.

Phase 3 Trial

Unlike Phase 1 and Phase 2 Trials which involved only relatively fewer number of subjects, this phase 3 trial is larger and requires a large number of test subjects say from 300 - 3000 on average. The amount of test subjects depends on the disease under consideration. The phase 3 trials assure in developing the trials to find the definite amount of dosage and side effects caused by the drugs in comparison with the currently available ‘best standard treatment’ the ‘gold’ treatment. They require very large amount of test subjects and are multi centered. Test subjects may be subjected to the trials from various centers in the country or in various countries. Due to its vast requirement, it is highly expensive and time consuming. Along with these, it is highly complex to design and conduct trials, since the definite value of dosage and side effects are to be predicted.

The phase 3 trials continue to exist and test subjects even while the regulatory information for the usage of the drug is submitted to the concerned regulatory agency. This is an opportunity to serve the medicines which could be life saving for the patients considered until the drug is actually available on market for purchase. The phase 3 trials are alternatively performed for the sponsors for what they call as ‘label expansion’. The label expansion is to include the patients or animals, for them the drug works other than the patients considered for the disease under study. For example, a drug might have developed to cure body pain, but it can also be used on mild doses for headache, then the label expansion will include this information. The label expansion cannot be done simply, some phase III b companies take phase III b studies to support data for the label expansion procedure for the medical company.

Once a drug is approved, the information on the tests conducted, methods, test subjects, trials, designs, and the conditions involved are all compiled together which forms the regulatory submission. The entire compilation includes the method of preparation, its effects on animals, humans, formula, and manufacturing process. The regulatory authorities verify these and may approve the company or sponsor for marketing of the drug. Once in the market also, the drug is constantly under the phase III trial. If the drug is well and does not prove any adverse side effects, the drug goes on sale on the market for the consumers. However, if an issue arises on the side effects the drug caused or the toxicity of the drug is identified or a consumer reports an abnormal result of using the drug, the drug has to be recalled from the market from future sale.

Aims of Phase 3 trials

Phase 3 trials are aimed to find out
1.    How effective is the current treatment in comparison with the already existing best standard of treatment
2.    Idea to get a broader view on how the treatment works as a whole
3.    All the phase trial results are sometimes combined to form the Meta analyses.
4.    The side effects of the drug once released onto the market

Conclusion

With combining the results from phases 1, 2 and 3 trials, it is easy to determine how well the treatment identified now works in comparison with the treatment already available. By using these results, they can be used for estimating the effectiveness of the drug to all kind of people who can use it. In addition, the toxicity of the drug can be reported by public and the company can revise it.

Clinical trials are conducted on individuals to identify the functioning of a drug, its safety, tolerance and other effects of the drug within the body. The clinical trials are performed usually on one center in a country or if needed multiple centers in the country. With these clinical trials, newer products are brought into market. When a drug is introduced in the market, it has to undergo various trial phases. This includes phase 1 to phase 4. In phase 1 trial, the drug is used and checked for its tolerance and safety limit. With the data manipulated, the organization manages the data collected and carries it over to the phase 2 trials.

Phase 2 trial

The phase 1 trial is performed to a smaller group of individuals. Usually 20 - 80 people are involved in the phase 1 trials. Not all drugs tested in the phase 1-trial passes to the phase 2 trials. Sometimes the drugs may be eliminated due to adverse side effects with even the minimum dose range in the phase 1 trial itself. However, typically if a drug is tested to fail, it is through the phase 2 trials. Phase 2 trials typically involve a larger group of test subjects from 20 - 300.

The drugs effects of pharmacokinetics and pharmacodynamics are again tested, but with a larger group of volunteers. The drug tests fail and the drug is rejected if the test results are not as planned or the tolerance to the drug is high. The toxicity of the drug can be well identified with the phase 2 trials. Phase 2 trials continue to assess the phase 1 trials with the larger number of volunteers. The phase 2 trials include the early clinical preliminary studies to obtain the preliminary data results of the drug behavior for a particular symptom or a specific disease or a specific condition of patients. This test also helps to determine the short-term side effects of using the drug and the common risks associated with using the drug and the dosage of the drug. Phase 2 trials are well controlled and monitored under supervision of experts.

Characteristics

Phase 2 trials are sometimes written as phase II. The trials of the Phase II are even further classified as Phase II a and Phase II b.

Phase II a:
This test is performed to assess with the dosage requirements. The dose escalation study is employed here. The groups of test subjects are given various dosages of the drugs over a period. Their test results are manipulated over a period to identify any effect caused due to the dosage of the drug.

Phase II b:
This test is usually performed to study how well the drug works with the subjects at the doses specified. For example, some drugs may work well for with minor dosage for age limits 15-18, while some may require higher dosage, depending on age factors, stage of the disease or the symptoms. All such things are analyzed in the phase II b trials.

Sometimes trials of phase 1 and phase 2 are combined and performed together to study the effects of the drug. The trials of phase II are either case series, where the subjects are given treatments and tracked with a similar treatment that was used previously for curing the disease. Other design of the trial may include randomized trial 2, in which case, few patients randomly receive the drug/dosage and few others receive normal treatment / standard treatment for the cure of the disease. Such variety of patients or subjects are compared over a period and evaluated.

Aims of Phase II trials

The phase II trials aim in finding out,

1.    If the treatment of the phase 2 works good enough to pass to the Phase 3 trials
2.    Which stages or type of disease considered, the treatment works well. Example: cancer. Various types of cancer patients may be involved. The drug may perform well for leukemia rather than lung cancer. Under circumstances, the effectiveness of the treatment is evaluated specific to the type of the cancer.
3.    Greater information on the dose and side effects of the drug used and how to manage them

The phase 1 trials include the dosage and side effects. Still, the doctors may not know the side effects occurring in the patients, which he might consider is a normal effect. Such information and details on the side effects of the drug and the drug dosage are finally evaluated.

With a relatively more population of several hundred people, the phase 2 trials perform the task very similar to Phase 1 trials. However, when slight side effects are not identified in phase 1 trials, they are identified and the treatment is tested for its effectiveness. When the treatment is found as good as the one available now, or much better than the one, the drug passes on to the larger phase 3 trials.

A phase 1 clinical trial comprises the preliminary tests performed on a smaller group of human subjects. Here the human subjects taken for the clinical tests are really smaller in amount, i.e. about 20 to 80 persons are considered for the trial. The human subjects are normally healthy volunteers. The phase contains tests that are used to determine the drug tolerance and safety limit of the drug. For example, some drugs on continuous usage they themselves become a burden. Similarly, the tolerance to some drugs may be limited by the human beings. Such features of the drug called the pharmacokinetics and pharmacodynamics are evaluated in the phase 1 tests.

The best place to perform these tests is an inpatient clinic, where there are full time staffs that can monitor the subjects closely. The subjects who have been injected with the drugs are monitored for over several half-life of the drug is completed. The half-life of the material is the time taken for the material to lose half of its activities, which may be physiologic, radioactive, or pharmacologic. Dose ranging of the drug are also included normally in the phase 1 trials. The tested dose ranges are very less and do not cause harm in animal testing. The human subjects sometimes could be the patients themselves. For example, in cancer and HIV drug testing, the patients themselves are volunteered. The sponsors or the pharmaceutical industries pay the volunteers for their inconvenience in time spent for the tests. Pay ranges may vary from smaller amount to huge amount as much as $4000 depending on the time spent.

Kinds of Phase 1 Trials

There are various kinds of phase 1 trials. They are,
SAD:
It stands for Single Ascending Dose. Here in this test, small groups of subjects are given single dose of the drug. If the subjects do not exhibit any adverse effects over a period of time from the drug, then the pharmacokinetics of the drug data are calculated to be on the line. So, the safety limits are within. Then a set of new subjects are given higher dose. This is repeated as long as the safety limit of using the drug is reached or an effect shows up due to intolerance to the drugs. This is the point where the drug has reached its Maximum tolerated dose (MTD).

MAD:
It stands for Multiple Ascending Dose. Here the group of individuals are given multiple dose of the drug and their blood samples and other body fluids are checked for the activity of the dose within the body and they are analyzed. This MAD testing is usually done for better understanding of the pharmacokinetics and pharmacodynamics of the drug. The dose of the drug is increased for small to a maximum amount of predetermined level.

Food Effect:
The varying effect before eating or after eating is tested here. Two healthy subjects are given doses of the drug over a period of time, one while fasting and the other during well fed.

Aims of Phase 1 Trial:

Phase 1 trials are conducted to find out

1.    Safe dosage range of the drug tested. This is done by the SAD and MAD tests on the subjects chosen
2.    Side effects. Again, with the SAD and MAD tests, the side effects or the adverse effects of the drug can be identified.
3.    How the body cope with the new drug. This is very essential. Since, a drug may cure a disease, but it may leave the body vulnerable to other attacks or the drug itself may affect the body.
4.    If the treatment has shrunk the occurrence of the disease. The treatment in this phase itself could be enough for shrinking the effects of the disease. Such possibilities are analyzed.
5.    The ‘dose escalation study’ is performed with the dose of the drug.

The phase 1 trials are performed on individuals of smaller quantity. The results manipulated are carried over to phase 2 trials investigations are not actually used to identify the perfect working of the drug on the individuals. However, with these phase 1 trials the adverse effects, tolerance limits of the drug is identified and used for performing other tests.

Aims of phase 1 trial:

Phase 1 trials are conducted to find out,
1.    Safe dosage range of the drug tested. This is done by the SAD and MAD tests on the subjects chosen
2.    Side effects. Again, with the SAD and MAD tests, the side effects or the adverse effects of the drug can be identified.
3.    How the body cope with the new drug. This is very essential. Since, a drug may cure a disease, but it may leave the body vulnerable to other attacks or the body may be affected by the drug itself.
4.    If the treatment has shrunk the occurrence of the disease. The treatment in this phase itself could be enough for shrinking the effects of the disease. Such possibilities are analyzed.

5.    The ‘dose escalation study’ is performed with the dose of the drug.

Aims of Phase 2 trials:

The phase II trials aim in finding out,
1.    If the treatment of the phase 2 works good enough to pass to the phase 3 trials.
2.    Which stages or type of disease considered, the treatment works well for.
3.    Example: cancer. Various types of cancer patients may be involved. The drug may perform well for leukemia rather than lung cancer. Under circumstances, the effectiveness of the treatment is evaluated specific to the type of the cancer.
4.    Greater information on the dose and side effects of the drug used and how to manage them.

Aims of Phase 3 trials:

Phase 3 trials are aimed to find out,
1.    How effective is the current treatment in comparison with the already existing best standard of treatment
2.    Idea to get a broader view on how the treatment works as a whole
3.    All the phase trial results are sometimes combined to form the Meta analyses.
4.    The side effects of the drug once released onto the market

Clinical trials are often considered as the ways to test a new drug or medicine. However, they can also be used to diagnose or prevent a disease from occurrence. The various types of clinical trials currently in use are,

Prevention trials:

1. The substances or the ways that could cause a particular disease are seen in these prevention trials.
2. For example: the lung cancer is caused by excessive smoking and smoking long time. While performing prevention trials, this is identified.

Screening trials:

1. The stage of diagnosis of a disease is done in screening trial.
2. It is performed to see the stages of development of the disease and the stage when it can be cured.

Diagnostic trials:

1. This is performed to perfectly identify the presence of the disease in the person.
2. This trial more accurately determines the stage of the disease.

Treatment trials:

1. Here the effectiveness of drugs, surgery, or radiations that can cure the disease is tested.
2. For example: cancer in its earliest stages can be cured by radiations. The Treatment trials involve using radiations; medications etc and try to cure the disease.

Support care trials:

1. They are also known as the quality of life trials.
2. They are done to study the ability of the drug to suppress the behavior or symptom of a disease.
3. Sometimes a procedure can also suppress the symptom of a disease. All these are studied in this trial.

Phases of clinical Trials

There are three phases of trials. They are phase 1, phase 2 and phase 3 trials. Each is performed at various levels and has various goals.

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Things to consider for Clinical Trial

People should know about the clinical trial as much as possible. They must be comfortable with the tests and take them with interest. This could lead to better results. In addition, for people who want to contribute to the medical field, these tests are great start. For few, the clinical trials can afford economical living.

Potential risks

The clinical trials are generally associated with few known and unknown risks. They are

•    the drug may cause a greater side effect on the patient, which could be irreversible or even life threatening
•    the drug may not be effective to a particular participant
•    the protocol may need the participant to spend more time and attention than the standard requirements, which may require the participant to visit the clinic often and meet with the staff and report

Potential benefits

The clinical trials are even more beneficial

•    They get the participants or patients with good and active health care
•    The patients or participants are exposed to newer researches that could be life saving until the drug is available for sale on the market
•    Since the staff are often specialist on the field, the affected patient is exposed to a greater care and can possibly get a better treatment without spending money
•    It contributes to the medical research

Other considerations to the participant

The test subjects are paid some amount of money as compensation due to time spent or their discomfort in using the drug during any part of the trial. The compensation amount will vary depending on the time spent on the trial. The more the time and stay longer, the compensation can be higher. In addition, some companies provide the participant with the drug even after the trial period ends which can benefit spending amount on purchasing the drug, while some companies do not. The amount to be paid and other information regarding the compensation amount and payment options are spoken with the potential participants before the consenting process while the applications are accepted. This information can also be included in the clinical trial protocol. Some organizations, companies or sponsors or the federal agency conducts the clinical trials. So, the venue or location of the tests will be informed to the participants. The locations usually are universities, doctor’s clinic, inpatient clinic where every participant gets individual attention under the supervision of a staff.

Purpose of clinical trial

Clinical trials are conducted to answer specific health questions. They are done to study:

1.    Newer prevention options on certain diseases they may be threatening
2.    newer treatment options that are much more effective than the ones currently available
3.    newer screening and diagnostic tests for certain diseases which are very much essential
4.    for improving the quality of medicines received by patients with serious medical conditions

A protocol is a predefined set of principles used. Similarly, a clinical trial protocol contains a study plan that has to be carried over in the form of clinical trials. The protocol includes information that includes the type of people who can participate in the clinical trial, number of participants, methods used to perform the clinical trials, procedures followed during the trial, dosage of medicines to be given during the trial, schedule of the tests and the time limit of performing the trial. It aims at safeguarding the participants’ health without any adverse effects. The clinical trials are performed generally in an inpatient atmosphere, where the staff can monitor the participants’ health and effectiveness of the drug or its adverse effects.

The staffs generally are doctors or nurse well versed in the field of test. When clinical trials are considered at multiple centers following different procedures it results in confusion and wrong analysis of the available data. That is the reason; the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has standardized the clinical trial protocol based on the Good Clinical practice guide. In most countries like USA, Japan, China, and European Union, the protocol is standardized. Therefore, when the clinical trials are run on various centers, they still follow exactly the same procedures and same tests. Therefore, with the data generated, all the data can be grouped and analyzed as though they have been obtained by working together.