Randomized trials are an accurate method to identify a causal relationship between therapy and the outcome of a disease, and in addition, the effectiveness of treatment.
general information
In the modern world there are many drugs used to treat various diseases. According to advertisements of drug manufacturers, they are all effective and have virtually no contraindications and adverse reactions. However, the levels of proven effectiveness are different for them. New drugs undergo numerous tests before appearing in the pharmacy network. It should be noted that about 90% of them are rejected at the stages of clinical trials.
Evidence based medicine
Since ancient times, various medications have been used to treat ailments. And only since the nineteenth century began to think about the effectiveness of drug therapy and the possibility of using scientifically-based mathematical approaches in assessing the quality of treatment. Evidence-based medicine - such a concept was first voiced by epidemiologists of a Canadian university when developing a training program in practical medicine. Doctor D.L. Sackett formally defined the term.
Evidence-based medicine is the accurate, conscious, common-sense use of the results of clinical trials confirming the safety and effectiveness of any treatment methods that are best at a given moment. Clinical studies may refute therapeutic treatments that have been successfully used in the past and have yielded good results. And they also form other approaches to treating patients.
Here is one example. During testing of antiviral drugs, it was found that they reduce the risk of pneumonia as a complication after the flu. Therefore, WHO (World Health Organization) made recommendations in which antiviral drugs were included for the treatment of this disease. In the modern world, when choosing a therapy for treating patients, medical workers rely on evidence-based medicine and try to use new drugs. Evidence-based medicine provides an opportunity to predict the course of the disease in a particular individual based on similar cases that have been studied previously.
Placebo - what is it?
This is a substance that in appearance is similar to the test drug, but does not have its properties and does not harm a person when taken. The drug is considered to be effective, the use of which, according to statistics, differs from the placebo drug.
In this case, one important condition must also be fulfilled, namely, the doctor and the patient do not have the right to know what exactly the patient is taking. This technique is called the double blind method. In this case, the subjective opinion of medical workers about the therapy and the indirect effect on the individual are excluded. There is a triple blind method. In this case, the person who tracks the results of the study does not have information on how the patient groups, including the placebo groups, are selected.
Scientific research
Tests are conducted with the participation of individuals in order to assess the effectiveness and safety of a new drug or to expand the indications of a drug already available on the market. Clinical research is an integral stage in the development of new drugs, it precedes its registration. During an experimental study, the drug is studied in order to obtain information about its safety and effectiveness. And already on the basis of the data received, the authorized body of the health system makes a decision on the registration of the drug or refusal.
Medicines that fail these tests cannot be registered and enter the pharmaceutical market. According to the Association of Developers of America, as well as manufacturers of medicines for medical use, of the ten thousand drugs that were developed, only 250 entered the preclinical testing phase. In the next stage, i.e., in clinical trials, only five fall, of which only one is subsequently used by practicing doctors. Clinical studies provide knowledge to both medical professionals in terms of more precise prescriptions and patients in terms of informing about possible adverse reactions and contraindications.
Clinical Research Stages
There are several phases to experimental research.
The first one takes about a year. During this period, indicators are studied: distribution, metabolism, absorption, output, dosage level, and the most convenient dosage form is selected. Healthy volunteers assist in this trial.
In the case of studies of drugs with high toxicity, people with an appropriate pathology are attracted. Tests in such situations are carried out in specialized healthcare institutions, which have the necessary equipment and trained medical personnel. The participation of volunteers, and they usually require from 20 to 30 people, is encouraged in research materially.
The second - during this period, the dosage regimen and dosage of the drug for the subsequent phase are determined. A group of volunteers from 100 to 500 people is recruited.
The third is a randomized study in which a large number of people take part (three or more thousand). In this phase, the data obtained in the second stage on the efficacy and safety of the drug in a certain group are confirmed or refuted. In addition, the dependence of the action of the drug on the dose taken is studied and compared, as well as the administration of the drug at different stages of the disease or its simultaneous use with other drugs.
Fourth - at this stage, clinical trials are carried out, necessary to obtain additional information about the effect of the drug, including with the aim of detecting rare, but very dangerous side effects during prolonged use in a large group of volunteers.
Required Requirements
For the reliability of scientific research when testing drugs requires compliance with certain rules, due to the implementation of which false results are minimal.
- Large sample. The more patients studied, the lower the error.
- Statistical processing of the data. It is carried out taking into account those parameters that are studied and the sample size. In this case, the error should not exceed seven percent.
- Controls or placebo groups. These are patients receiving a placebo drug in place of the study drug or standard treatment.
Types of Clinical Trials
Several types are known, each of which has both advantages and disadvantages.
- Instantaneous, or transverse. A group of patients is examined once. The cost of this type of research is small. Using it, you can evaluate the statistics of the incidence and course of the disease at a certain point in the study group. The dynamics of the disease can not be detected.
- Longitudinal, or cohort. This type of research is considered the most evidence-based and is often carried out. A group of volunteers has been monitored for a long time. The cost of its implementation is high; it is carried out simultaneously in several countries.
- Retrospective. Cheap type of test, evidence base is low, therefore unreliable. Used to determine risk factors. The data of previous studies are being studied.
Randomization or random distribution
This is another rule that must be followed. Patients participating in the study are grouped into spontaneous groups regardless of age and gender, i.e., random selection of candidates occurs, which eliminates the influence of these factors on the results of the study.
Controlled placebo-randomized trials using the blind double or triple method got the name “gold standard”. Thanks to such tests, the information received is most reliable. Unfortunately, due to the rather high cost and complexity, they are rarely carried out. In accordance with the basic tenets of evidence-based medicine, to make a decision on the treatment tactics of a patient, physicians must be guided by a standardized international classification of clinical trials.
Difficulties
The complexity of volunteer selection is considered one of the serious and difficult problems faced by research experts. Basically, about six percent of patients can be included in a single-disease group.
Thus, the results obtained apply only to patients who are identical in characteristics to those studied in groups. Therefore, it is not possible to recommend them for use in other conditions without obtaining a new test result. In addition, it should be noted that randomized trials are not at all the exception of erroneous results in the analysis.
Types of Controlled Tests
They can be:
- One-center when research is carried out in one health facility. Difficulties - it is difficult to make a selection according to all the studied attributes in a short time.
- Multi-center. Several medical organizations are involved in the process, and all work on the same protocol.
- Open. A volunteer and a doctor, after randomization, have information about the type of treatment.
- The blind. The doctor learns about therapy after randomization, and the subject will not know about it (this question is agreed upon in advance and a citizen voluntarily agrees to participate in the research process).
- Double blind. In this case, neither the volunteer nor the doctor knows what type of intervention a particular individual will have.
- Triple blind. This type of test implies that the doctor, the test person and the researcher himself, who processes the results, do not have information about the type of intervention.
Disadvantages of Randomized Controlled Trials
Due to high material costs and a long period:
- tests are carried out over a short period of time on a small group of volunteers or most of the studies are not carried out at all;
- in connection with the payment of tests by pharmaceutical companies, research institutes, universities, their direction is also indicated;
- indirect criteria are used instead of clinical ones.
Systematic errors occur for the following reasons:
- the inclusion in the group of only those volunteers who will give a predictable result when taking the drug;
- imperfect randomization;
- awareness of researchers about finding patients in specific groups, i.e., the blind method is not respected.
Benefits of Randomized Controlled Trials
- The effectiveness of the drug is evaluated compared with the placebo drug in certain groups, for example, in men aged 40 to 50 years.
- Accumulation of information after the study.
- The goal may not be the ability to confirm your own hypothesis, but an attempt to falsify.
- The exception is an error, since there is a comparison in other identical groups.
- The ability to combine the results from several studies (meta-analysis).
Randomized trials are controlled trials with a double or triple blind control method, belonging to the first class. The materials and information obtained from their results, as well as the meta-analysis used in the practice of medical professionals as the most reliable source of information.
Conclusion
For the introduction of evidence-based research into medical practice, it is necessary to clearly describe the groups of volunteers who studied the effect of the drug to treat a specific pathology. Clearly state the selection criteria and the reasons for exclusion from the test of patients, as well as evaluate the results by means available in practical medicine.