What does " clinical trial»?
A clinical trial is a scientific study involving humans that is conducted to evaluate the effectiveness and safety of a new drug or to expand the indications for use of an already known drug.
Clinical trials around the world are an integral stage of drug development, which precedes its registration and widespread medical use. During clinical trials new drug is being studied to obtain data on its effectiveness and safety. Based on these data, the authorized health authority makes a decision on registration of the drug or refusal to register. A drug that has not passed clinical trials cannot be registered and brought to market.
When developing a new drug, it is impossible to do without clinical trials, since extrapolation of the results of studies in animals and biological models to humans is possible only in general view, and sometimes it is impossible at all. For example, pharmacokinetics (how a drug enters the bloodstream, is distributed in the body, and is eliminated from the body) in humans differs even from the pharmacokinetics in primates. However, analysis of preclinical studies is very important for assessing the likelihood of development and nature of side effects, calculating the starting dose for studying the properties of the drug in humans.
Clinical studies can be initiated only after encouraging results have been obtained in preclinical studies (studies on biological models and laboratory animals), as well as the approval of the ethical committee and a positive decision from the authorized health authority of the country where the study is planned to be conducted.
Initially experimental medicinal product is being studied in a small number of patients and/or healthy volunteers. As data on its safety and effectiveness accumulate, the number of patients involved in the study increases, and the drug itself is compared with already known and widely used drugs. medical practice medications.
Types of Clinical Trials
The first way to classify clinical trials is by the presence of interference in the usual tactics of patient management, that is, in standard procedures for examining and treating the patient.
Observational (observational) study - a clinical study in which the researcher collects data by simply observing events in their natural course, without actively interfering with them.
Non-interventional study (“non-intervention study”) is a study in which a medicinal product is prescribed in the usual manner in accordance with the conditions set out in the marketing authorization. The question of whether a patient is “allocated” to a particular treatment strategy is not decided in advance in the study protocol. This issue is resolved in accordance with current practice, and the prescription of a drug is clearly separated from the decision to enroll a patient in a study. No other diagnostic or monitoring procedures are used for patients, and epidemiological methods are used to analyze the data collected.
Interventional research is a study of new, unregistered drugs, immunobiological agents, medical equipment, or a study in which drugs, immunobiological agents, medical equipment are prescribed or used in a manner different from the conditions set out in the registered instructions for use (whether it is a new indication, a new drug dosage, new way introductions new way application or a new category of patients).
The criterion for another method of classification is the purpose of the study. This classification method was proposed by the U.S. National Institutes of Health (NIH) and identifies six different types of clinical trials:
- Prevention trials are conducted to find the best ways to prevent diseases in people who have never had them or to prevent relapses in patients. Such studies may examine medications, vaccines, vitamins, minerals, and lifestyle changes.
- Screening trials are conducted to find best way detection of certain diseases or conditions.
- Diagnostic trials are conducted to find the best way to diagnose a certain disease or condition.
- Treatment trials are conducted to study the effectiveness and safety of experimental drugs, new drug combinations, or new techniques in surgery or radiation therapy.
- Quality of life trials are conducted to explore ways to improve the quality of life of patients suffering from chronic diseases.
- Expanded access programs (under exceptional circumstances - compassionate use trials or expanded access) involve the use of an experimental drug in patients with serious or life-threatening diseases that cannot be included in a clinical trial because they do not meet the inclusion criteria. Typically, such programs attract patients for whose diseases there are no effective treatments, or those who have tried all the standard, well-known treatments and for whom they have not helped.
Clinical trial design
Research design is overall plan research, a description of how the research will be conducted.
The main types of observational studies are cohort studies and case-control studies, etc.
- In a cohort study, a selected group of people (cohort) is observed over a period of time. The status of patients in different subgroups of this cohort, those who were or were not exposed (or were exposed in to varying degrees) treatment with the study drug are compared. In a prospective cohort study, a study plan is first drawn up and the procedure for collecting and processing data is determined, then cohorts are drawn up, the study is conducted and the data obtained are analyzed. In a retrospective cohort study, a cohort is selected from archival records and the health status of patients is tracked from the start of observation of the patient to the present.
- A case-control study compares people with a specific disease with people from the same population who do not have the disease to identify associations between clinical outcome and prior exposure to certain risk factors.
There are other types of observational projects - for example, cross-sectional observational study (single-point epidemiological study), etc.
The reference design for clinical trials is randomized, controlled, double-blind trials.
The randomization procedure means that patients are randomly assigned to treatment groups and have the same opportunity to receive the study drug or the control drug. The course of treatment prescribed to a patient usually has an effect regardless of whether he receives the active drug or not. The placebo effect must be taken into account. Today, two main control technologies are used - placebo control and active control. Placebo control means that patients in the control group are given a placebo - a product that does not contain the active principle, which in shape, color, taste, and smell completely imitates the drug being studied. If an active treatment method is used for control, the drug being studied is compared with an already known and widely used therapy today (the so-called “gold standard”).
Giving patients in the control group a placebo raises ethical concerns because it may limit their right to receive the best treatment available today. The use of placebos is limited. The World Medical Association (WMA) Declaration of Helsinki specifies that placebos are used only in two cases:
- firstly, if effective way there is no treatment for the disease,
- second, if compelling scientifically sound methodological reasons are presented for using placebo to evaluate the effectiveness or safety of a drug, and patients receiving placebo or no treatment will not be at risk of causing serious or irreversible harm to their health.
Psychological, or so-called subjective factors, play a great importance when conducting clinical studies. For example, the patient's knowledge that he is receiving therapy active drug, may affect the assessment of the safety and effectiveness of therapy. A physician-researcher who is convinced of the benefits of one of the drugs being compared may unwittingly interpret improvements in the patient's health status in its favor or try to prescribe to a patient with a more severe illness what he considers more effective. To minimize the influence of subjective factors, a blind research method is used.
A study in which the patient does not know and the researcher knows what treatment the patient is receiving is called single-blind. If neither the patient nor the investigator knows about the treatment, the study is called double-blind.
Blinded studies minimize the possibility of intentional biases, and unintentional biases are distributed equally between groups.
Clinical trial protocol
A protocol is a document that describes the purpose, objectives, design, methodology, statistical aspects and organization of the study. Any clinical trial begins with the development of a protocol. This is the most important document of a clinical trial.
Having studied the protocol, authorized health authorities and ethical committees assess the adequacy of the scientific objectives and methodological approaches, the effectiveness of measures to protect the rights of study participants, and decide on the possibility of conducting a clinical trial. During the study, the protocol serves as a guide for the researchers. It allows you to unify the work of research centers around the world. After completion of the study, the protocol is the basis for conducting statistical analysis and a document on the basis of which the study is checked by auditors and inspectors of authorized health authorities.
The protocol for a large study can take several years to develop, and not only employees of the sponsoring company, but also external consultants take part in the work on it.
Informed consent
Informed consent is a process that allows a patient or healthy volunteer to freely confirm their desire to participate in a clinical trial. Informed consent is also a document signed by study participants (patient and researcher). The research physician informs the patient about all aspects of the clinical trial that may affect the decision to take part in the experiment (benefits, risks, time costs, possible side effects, etc.). Therefore, such consent is called informed consent. After all aspects of participation in a clinical trial have been explained to a potential research participant, the investigator provides the patient with written information that describes the details of the trial (duration, procedures, risks, potential benefits, etc.). After carefully studying the document again, the participant decides whether he should sign the consent or not.
A study participant can withdraw from the study at any time without explanation.
Research power
When planning a clinical trial, the sponsoring company, with the help of bio specialists, medical statistics determines how many patients need to be enrolled in a study to obtain a statistically significant result showing a difference in the effectiveness of compared therapies. The number of patients is determined before the start of the study, and the cost of the study depends on it. Based on the cost, the sponsoring company decides on the feasibility of conducting the study.
The number of patients needed to obtain a statistically significant result depends on the disease, the parameters studied, the design, etc. For example, to show the effectiveness of a new drug in the treatment of incurable metastatic kidney cancer in a placebo-controlled study, many fewer patients are needed than in a placebo-controlled study of a well-curable disease. ovarian cancer. The fact is that if the patient can recover without treatment, then spontaneous cases of improvement will “muddy up” the effect of therapy. To identify exactly the part of patients who benefited from the drug, it is necessary to recruit a large number of patients and separate them from those who recovered thanks to standard treatment. If the health status of patients immediately deteriorates sharply without treatment, then the effect of therapy will be visible in a small group - the health status of those who receive effective treatment, will not get worse immediately.
The characteristic of a study that is capable of detecting clinically important differences between the study drug and the comparator drug (eg, in efficacy), if such differences actually exist, is called the power of the test. The larger the sample of patients, the greater the power of the test.
To reliably show a small difference, more patients would need to be recruited. However, by increasing the number of patients, it is possible to statistically prove the presence of such small differences that they will no longer have clinical significance. Therefore, a distinction is made between statistical and clinical significance.
Clinical trial phases
Preclinical studies include in vitro studies ( laboratory research test tubes) and in vivo studies (studies on laboratory animals), in which different doses of a test substance are examined to obtain preliminary data on pharmacological properties, toxicity, pharmacokinetics and metabolism of the drug being studied. Preclinical studies help pharmaceutical companies understand whether a substance is worth exploring further. Human studies can begin if data from preclinical studies shows that the drug can be used to treat a disease, if the drug is reasonably safe and the studies do not expose people to unnecessary risks.
The drug development process is often described as a sequential series of four phases of clinical trials. Each phase is a separate clinical trial; registration of a drug may require several studies within the same phase. If the drug successfully passes trials in the first three phases, it receives a marketing authorization. Phase IV studies are post-marketing studies.
Phase I
Phase I studies typically involve 20 to 100 healthy volunteers. Sometimes high toxicity of the drug (for example, for the treatment oncological diseases and AIDS) makes conducting such studies in healthy volunteers unethical. Then they are carried out with the participation of patients suffering from the corresponding disease. Typically, phase I studies are conducted in specialized institutions where the necessary equipment and specially trained personnel are available. Phase I studies may be open-label and may use a baseline control method. In addition, they may be randomized and blinded. The purpose of phase I studies is to establish tolerability, pharmacokinetic and pharmacodynamic parameters, and sometimes to provide a preliminary safety assessment.
Phase I studies include absorption, distribution, metabolism, excretion, preferred dosage form and safe dosage level. Phase I usually lasts from a few weeks to 1 year.
Remuneration is paid for participation in the study.
There are different types of phase I studies:
Single Ascending Dose studies (SAD) are studies in which a small number of patients are given a single dose of the study drug for the entire duration of their observation. If no adverse reactions are detected and the pharmacokinetic data correspond to the expected level of safety, then the dose is increased and the next group of participants receives this increased dose. Administration of the drug with dose escalation continues until pre-targeted pharmacokinetic safety levels are achieved or unacceptable adverse reactions are detected (at which point the maximum permissible dose is said to have been reached).
Multiple Ascending Dose studies (MAD) are studies conducted to better understand the pharmacokinetics and pharmacodynamics of a drug when administered multiple times. In such studies, a group of patients receive low doses of the drug over and over again. After each administration, blood and other bodily fluids are drawn to evaluate how the drug behaves in the human body. The dose is gradually increased in following groups volunteers - up to a predetermined level.
Phase II
Having assessed the pharmacokinetics and pharmacodynamics, as well as the preliminary safety of the investigational drug in phase I studies, the sponsoring company initiates phase II studies in a larger population (100-500 people).
Phase II study designs may vary, including controlled studies and baseline studies. Subsequent studies are usually conducted as randomized controlled trials to evaluate the safety and effectiveness of a drug for a specific indication. Phase II studies are usually conducted in a small, homogeneous patient population selected according to strict criteria.
An important goal of these studies is to determine the dosing level and dosing regimen for phase III studies. The doses of drug that patients receive in phase II studies are usually (though not always) lower than the highest doses that were administered to participants in phase I. An additional task during phase II studies is the evaluation of possible endpoints, therapeutic regimens ( including concomitant medications) and target group identification (e.g. light form against heavy) for further research during phase II or III.
Sometimes phase II is divided into phase IIA and phase IIB.
Phase IIA is a trial study designed to determine the level of safety of a drug in selected groups of patients with a specific disease or syndrome. The objectives of the study may include determining the sensitivity of patients to various doses of the drug depending on the characteristics of the patient group, frequency of administration, dose, etc.
Phase IIB studies are well-regulated studies designed to determine the effectiveness and safety of a drug in patients with a specific disease. The main objective of this phase is to determine the optimal dosing level for phase III.
Some studies combine phases I and II so that both the efficacy and safety of the drug are tested.
In phase II, it is necessary to have a control group, which in terms of composition and number of patients does not differ from the group receiving the study drug. Patients in the two groups should be comparable in terms of gender, age and previous background treatment. In this case, the effectiveness and tolerability of the new drug is compared either with a placebo or with another active drug, which is the “gold standard” in the treatment of this disease.
Phase III
Phase III studies are randomized, controlled, multicenter studies involving large patient populations (300–3,000 or more, depending on the disease). These studies are designed to confirm the pre-assessed phase II safety and efficacy of a drug for a specific indication in a specific population. Phase III studies may also examine the dose-response effect of the drug or the drug when used in a broader population, in patients with varying degrees of disease severity, or in combination with other drugs.
Sometimes phase III studies continue after registration documents have already been submitted to the appropriate regulatory authority. In this case, patients continue to receive the life-saving drug until it is registered and goes on sale. There may be other reasons for continuing research - for example, the desire of the sponsoring company to expand the indications for the use of the drug (that is, to show that the drug works not only for the registered indications, but also for other indications or in other groups of patients, as well as to obtain additional information about safety). These types of studies are sometimes classified as phase IIIB.
Having confirmed the effectiveness and safety of the drug during phase III studies, the company creates a so-called drug registration dossier, which describes the methodology and results of preclinical and clinical studies of the drug, production features, its composition, and shelf life. The totality of this information constitutes the so-called “registration dossier”, which is submitted to the authorized health authority that carries out registration (each country has its own).
the drug is more effective than known drugs of similar action,
has better tolerability comparable to already known drugs,
effective in cases where treatment with already known drugs is unsuccessful,
more economically profitable
easy to use,
has a more convenient dosage form,
has a synergistic effect in combination therapy without increasing toxicity.
Phase IV
Phase IV is also known as post-marketing studies. These are studies conducted after the drug has been registered for its approved indications. These are studies that were not required for registration of the drug, but are necessary to optimize its use. The requirement for these studies may come from both regulatory authorities and the sponsoring company. The purpose of these studies may be, for example, to gain new markets for the drug (for example, if the drug has not been studied for interactions with other drugs). An important task of phase IV is the collection additional information on the safety of the drug in a sufficiently large population over a long period of time.
Also, the goals of phase IV may include assessment of such treatment parameters as treatment timing, interactions with other drugs or food products, comparative analysis of standard courses of treatment, analysis of the use of different drugs in patients age groups, economic indicators treatment and long-term results of treatment (reduction or increase in mortality among patients taking this drug for a long time).
In addition to phase IV intervention studies (in which the drug is used for a registered indication, but the examination and management of the patient is determined by the study protocol and may differ from routine practice), post-registration observational (non-interventional) studies can be conducted after the drug is approved in the country. Such studies collect information about how the drug is used by doctors in their daily clinical practice, which makes it possible to judge the effectiveness and safety of the drug in “real life” conditions.
If phase IV studies or post-marketing observational studies reveal rare but dangerous side effects, then the drug may be withdrawn from sale, its use may also be limited.
Phase division is a common but approximate way to classify clinical trials because the same trial may be conducted in different phases. For example, although pharmacological studies are typically conducted during phase I, many are initiated in each of the three phases but are still sometimes designated as phase I studies. The results obtained from a study often entail represents an adjustment to the entire research plan. For example, the results of a confirmatory therapeutic study may require additional pharmacological studies in humans.
Therefore, the most preferred classification criterion is the purpose of the study.
Clinical trial design
The design of a clinical trial is the plan for conducting it. The design of a particular clinical trial depends on the goals pursued by the study. Let's look at three common design options:
· clinical trial in one group (single group design)
· clinical trial in parallel groups (parallel group design)
· clinical trial in a “crossover group design”
Single-arm clinical trial
(single group design)
In a single-group study, all subjects receive the same experimental treatment. This study design aims to compare treatment outcomes with baseline conditions. Thus, subjects are not randomized to treatment groups.
The single-arm clinical trial model can be illustrated as follows:
Screening -- Inclusion -- Initial state -- Treatment -- Outcomes
The one-group model can be used in phase I studies. Single arm study designs are not typically used in phase III clinical trials.
The main disadvantage of the single-group study design is the lack of a comparison group. The effects of the experimental treatment cannot be differentiated from the effects of other variables.
Clinical trial in parallel groups
(parallel group design)
In parallel group clinical trials, subjects in two or more groups receive different treatments. For achievement statistical significance(to eliminate systematic error) subjects are distributed into groups using the method random distribution(randomization).
The parallel group clinical trial model can be illustrated as follows:
Treatment a -- Outcomes a
Treatment b -- Outcomes b
Where a, b -- various drugs or different doses or placebo
Clinical trials using parallel group designs are expensive, time-consuming, and require large numbers of subjects (with low event rates). However, clinical studies in parallel groups are the most objective in determining the effectiveness of treatment and accurate in drawing conclusions. Most clinical trials are therefore conducted in a parallel group design.
Sometimes parallel group studies can be used in two ways: factorial and heterogeneous models.
Factorial design-- this is a design based on several (more than 2) parallel groups. Such studies are carried out when it is necessary to study a combination of different drugs (or different doses of the same drug).
The factorial design of a clinical trial can be illustrated as follows:
Screening -- Enrollment -- Preparatory period -- Baseline -- Randomization --
Treatment a -- Outcomes a
Treatment b -- Outcomes b
Treatment with -- Outcomes with
Treatment in -- Outcomes in
Where a, b, c, d are different drugs or different doses or placebo
The factorial model is useful in evaluating drug combinations.
The disadvantage of the factorial model is the need to attract a large number of subjects and, as a result, increased research costs.
Withdrawal (Discontinuation) Design
A heterogeneous design is a type of parallel group study in which all subjects initially receive an experimental treatment, then, to continue the experimental treatment, patients with appropriate responses are randomized into either double-blind or placebo groups. This model is typically used to evaluate the effectiveness of an experimental treatment by stopping the drug immediately after a response occurs and recording relapse or remission. In Fig. Figure 5 shows a diagram of a heterogeneous research model.
Screening - Enrollment - Experimental treatment - Treatment response - Randomization of responders - Treatment or Placebo
The heterogeneous trial design is particularly effective for evaluating drugs intended to treat difficult-to-treat diseases. In such studies, only a small percentage of subjects respond to treatment.
During the treatment period, responses are identified, and a heterogeneous randomization phase is used to demonstrate that the response is real and not a placebo response. In addition, heterogeneous models are used to study relapse.
The disadvantages of heterogeneous models are:
· a large number of subjects who initially receive treatment to detect responses
· significant duration of the study
The preparatory period should last long enough for the patient's condition to stabilize and the effect of the drug to be more clearly identified. It should be noted that the percentage of subjects excluded from these studies may be high.
Ethical standards require careful consideration of the use of this research model due to the fact that it may require the exclusion of drugs that provide relief to patients. Rigorous monitoring and clear definition of endpoint metrics is paramount.
"Cross" model
(Crossover Design)
Unlike parallel group study designs, crossover designs allow the effects of both the study drugs and the comparison treatments to be assessed on the same subjects. The subjects are randomized into groups that receive the same course of treatment, but with a different sequence. As a rule, a “wash-out” period is necessary between courses to ensure that patients’ indicators return to baseline, as well as to eliminate the undesirable influence of residual effects of previous treatment on the effects of subsequent treatment. A “washing out” period is not necessary if the analyzes of the subject’s individual reactions are limited to their comparison at the end of each course, and the treatment period lasts long enough. Some "crossover" models use pre-crossover, meaning that patients who are excluded from studies at the treatment stage can be switched to groups alternative treatment ahead of schedule.
Screening - Preparatory period - Condition monitoring - Randomization - Treatment A in group 1 and Treatment B in group 2 - Washout period - Treatment B in group 1 and Treatment A in group 2
Crossover models are typically used to study pharmacokinetics and pharmacodynamics when the goal is to control for variability within a population of subjects. In addition, it is fair to assume that the effects of the first course do not affect the second course in pharmacokinetic and pharmacodynamic studies with a sufficient washout period.
Crossover designs are more economical than parallel group designs because fewer subjects are required. However, sometimes difficulties arise in interpreting the results. The effects of one therapy may be confounded with the effects of a subsequent one. It can be difficult to distinguish the effects of sequential treatment from the effects of individual courses. When conducting clinical trials, the crossover design usually requires more time than parallel group studies due to the fact that each patient undergoes at least two treatment periods plus a washout period. This model also requires obtaining more characteristics for each patient.
If the clinical conditions are relatively constant throughout the study period, then the crossover design is effective and reliable.
The relatively low sample size requirements make crossover designs useful in early clinical development to facilitate decisions regarding larger parallel study designs. Since all subjects receive the drug being studied, crossover studies are also effective for assessing safety.
RESEARCH DESIGN IN MEDICINE
Prof. A.O.Gusan
Publication of many scientific materials in the domestic and foreign press, as well as experience in editing collections scientific works Conferences of doctors of the Karachay-Cherkess Republic, now in their 11th year, with the participation of many domestic and foreign scientists, allow me to give some recommendations on the implementation of scientific research and the presentation of their results.
In each medical specialty, doctors use its own specific research methods. However, there are general principles methodologies and methods of research work that should be followed in the process of carrying out scientific work in any branch of medicine. Any scientific work must be carried out in accordance with international requirements main methodological and methodological approaches. This is an urgent requirement of the time, given the pronounced integration of Russian medical science into the world.
Unfortunately, to date, the methodology for planning scientific work and especially the issues of biostatistics have not been studied in medical higher education institutions. educational institutions, therefore, I consider it appropriate and useful to briefly consider the basic requirements that a doctor should follow when documenting the results of his scientific research.
In this information message we will focus on the most common form of presenting the results of scientific research - a scientific article.
A scientific article is a scientific work limited in scope, which sets out a reasoned system of views of the author on a specific issue. The most important requirements for a scientific article: the relevance of the issue raised in it, the depth of the phenomena, events and facts covered, the specificity and validity of the conclusions and generalizations made.
Any scientific research includes several blocks of interrelated stages. The first is pre-planned research, drawing up and approval of a research plan. The second includes the research process itself (collection of materials characterizing the problem being studied, accumulation of factual data about it, their systematization, development of certain ideas about the problem). The third part of the research is the presentation of the results of the scientific search (interpretation, report, publication).
When writing any scientific article, the author must provide an analytical review of the literature on the chosen topic justifying the need for this work. Most often, these may be questions on a given topic that have not been sufficiently covered to date, or the author puts forward new research methods that allow deepening knowledge on this issue, etc. The topic of the work may be clinical case, observation relevant for practical work experience, etc.
The next very important section of any research is the characteristics of its design. The results of research work are largely determined by the correctness of the chosen research methods. To evaluate the effectiveness of new methods of diagnosis, prevention and treatment, eliminate errors and correctly interpret the results of clinical studies, they must be carried out in the framework of randomized controlled trials, which are considered the “gold standard” for clinical comparisons.
A controlled clinical trial is a prospective study in which matched groups receive different kinds treatment: patients in the control group received standard treatment (usually the best according to modern concepts), and patients in the experimental group received new treatment. The most important condition for ensuring the reliability of a controlled study is the homogeneity of the group of patients in terms of all characteristics that influence the outcome of the disease (gender, age, presence concomitant diseases, severity and stage of the underlying disease, etc.). Considering the presence of many interrelated factors that determine the prognosis, as well as “hidden” prognostic factors, it is possible to achieve the most complete comparability of observation groups only by using the method of random distribution of patients into groups, i.e. randomization (random). True randomization presupposes mandatory compliance with the unpredictable nature of the distribution of patients into groups (the researcher cannot predict which group the next patient will fall into - “blind selection”). To increase the efficiency of randomization, preliminary stratification is carried out - the distribution of treatment options is carried out in homogeneous groups of patients formed according to leading prognostic signs (stratification randomization).
The section “Materials and methods of research” indicates the number of patients in the control and main groups, their homogeneity by gender, age, severity and presence of concomitant diseases. Reliable clinical results can only be obtained with a sufficient number of observations in both groups.
Determining the optimal number of observation cases is an important stage in experimental planning. Thus, in cases where the results of the study will be expressed qualitatively, much larger number observations than when using quantitative estimates, expressed as arithmetic averages. In addition, it should be remembered that a small number of studies reduces their accuracy and reliability. To increase the accuracy of the study by 2 times, it is necessary to increase the number of observations by 4 times. Moreover, the number of observed cases in the control and experimental groups does not have to be the same. The number of cases required to conduct an experiment is determined when planning research in each specific case individually using special formulas described in a number of reference books on medical statistics.
In accordance with the International Ethical Requirements for Biomedical Research Involving Human Subjects and the International Convention on Civil and Political Rights, all medical research with human participation should be built on three ethical principles: respect for the individual, achievement of benefit, justice. In all biomedical research involving human subjects (patients or healthy), the investigator must obtain informed consent from the subjects who will participate in the trial and, if the research subject (SR) is unable to give it, informed consent from a close relative or authorized representative. Informed consent means the consent of a competent SI who has received all the necessary information, understands it adequately and makes a decision freely, without undue influence, inducement or threat. The SI should receive information about the purposes, methods, duration of the study, expected risks or discomfort, alternative procedures, the degree of confidentiality, and the ability to withdraw from the study at any time.
The section “Material and research methods” should be described in such detail that any other researcher could, if desired, reproduce the work. At the end of this section, methods for statistical processing of the results obtained and the software used for this are indicated. Analysis of statistical data is carried out by appropriate mathematical processing of the results obtained, the techniques and methods of which are described in detail in special manuals on medical statistics. IN last years statistical processing of data began to be carried out on a personal computer using special software packages (for example, Statgraph, etc.), which make it possible to quickly calculate average values and relative coefficients, identify the nature and strength of the relationship, the degree of reliability, and construct analytical tables, charts and graphs.
The scientific processing of the research materials is completed in the “Results and Discussion” section and involves the following main elements: comparison of data, assessment of their reliability and the results of the study as a whole. This section usually includes the necessary illustrative material (tables, figures, graphs, etc.). It must be remembered that the description of the illustrations should not be a repetition of what has already been reflected in the text of the article.
The conclusions of the work must correspond to the title of the article, the goals and objectives set by the author.
The bibliography should contain all sources used. However, the citation system may be different. Every Science Magazine, the editors of any collection of works have their own requirements for the structure of the article, the design of illustrative material and the list of references used. In this regard, each author should familiarize himself with the rules of the publication to which he is preparing to submit his research materials.
In the domestic medical literature, the Harvard system is the most common. After referring to the author’s opinion, his initials, surname, and the year of publication of the work are indicated in parentheses. In the bibliography, sources are presented in alphabetical order by author's last name. A more advanced version of this system involves replacing the names of the authors and the year of publication with the serial number of the work in the attached list of references, also compiled in alphabetical order. This number is usually placed in square brackets.
You should carefully check the output data of each literary source, indicating the surname and initials of the author (or authors), the title of the article or section of the monograph, then the name of the journal or other printed edition, indicate the year (for books - year and place) of publication, volume, journal number, pages. First, a list of domestic authors is compiled in alphabetical order, then foreign ones.
Examples of compiling a list of references.
Samples of bibliographic writing of literature (GOST R 7.0.5-2008. Bibliographic reference. General requirements and rules for compilation. - M.: Standardinform. - 2008. - 19 p.)
1. VoyachekV. I. Fundamentals of otorhinolaryngology. - L.: Medgiz, 1963. - 348 p.
2. Blotsky A. A., Pluzhnikov M. S. The phenomenon of snoring and obstructive sleep apnea syndrome. - St. Petersburg: Spets.lit., 2002.-176 p.
3. Preobrazhensky B. S., Temkin Ya. S., Likhachev A. G. Diseases of the ear, nose and throat. - M.: Medicine, 1968. - 495 p. More than three authors
4. Fundamentals of audiology and hearing aids / V. G. Bazarov [et al.]. - M.: Medicine, 1984. - 252 p.
5. Borzov E. V. The role of perinatal factors in the formation of pathology of the pharyngeal tonsil // news of otorhinolaryngology and logopathology. - 2002. - No. 2. - P. 7-10.
6. Kovaleva L. M., Mefedovskaya E. K. Etiology and pathogenesis of sphenoiditis in children // News of otorhinolaryngology and logopathology. - 2002. - No. 2. - P. 20-24.
7. Vocal cord injection with autogenous fat: A long-term magnetic resona. nee imaging evaluation / J.H. Brandenburg // Laryngoscope. - 1996. - Vol. 106, N 2, pt. 1. - P. 174-180.
By the same principle, articles from collections of works and (or) abstracts of reports are cited.
Articles from collections:
8. Korobkov G. A. Rate of speech. Contemporary issues physiology and pathology of speech: collection. tr. Moscow Research Institute of Ear, Throat and Nose; Leningr. Research Institute of Ear, Throat, Nose and Speech. - M., 1989. - T. 23. - P. 107-111.
Theoretical validation in sociological research: Methodology and methods
IN social sciences There are a variety of types of research and, accordingly, opportunities for the researcher. Knowing about them will help you solve the most difficult problems.
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Research Strategies
In the social sciences, it is customary to distinguish two most common research strategies - quantitative and qualitative.
Quantitative strategy involves the use of a deductive approach to test hypotheses or theories, based on a positivist approach natural sciences and is objectivist in nature. A qualitative strategy focuses on an inductive approach to developing theories, rejects positivism, focuses on the individual interpretation of social reality, and is constructivist in nature.
Each strategy involves the use of specific data collection and analysis methods. The quantitative strategy is based on the collection of numerical data (coding data from mass surveys, aggregated testing data, etc.) and the use of mathematical statistics methods for their analysis. In turn, the qualitative strategy is based on the collection of textual data (texts of individual interviews, participant observation data, etc.) and their further structuring using special analytical techniques.
Since the early 90s, a mixed strategy began to actively develop, which consists of integrating the principles, methods of collecting and analyzing data from qualitative and quantitative strategies in order to obtain more valid and reliable results.
Research designs
Once the purpose of the study has been determined, the appropriate type of design must be determined. Research design is the combination of requirements regarding the collection and analysis of data necessary to achieve the objectives of the study.
Main types of design:
Cross-sectional design involves collecting data regarding large number units of observation. Typically involves the use of a sampling method to represent the general population. Data is collected once and is quantitative in nature. Next, descriptive and correlation characteristics are calculated, and statistical conclusions are drawn.
A longitudinal design consists of repeated cross-sectional surveys to establish changes over time. It is divided into panel studies (the same people take part in repeated surveys) and cohort studies (the same people take part in repeated surveys). different groups people who represent the same general population).
Experimental design involves identifying the influence of an independent variable on a dependent variable by leveling threats that may affect the nature of change in the dependent variable.
Case study designs are designed to study one or a small number of cases in detail. The emphasis is not on the distribution of the results to the entire population, but on the quality of the theoretical analysis and explanation of the mechanism of functioning of a particular phenomenon.
Research objectives
Among the goals of social research are description, explanation, evaluation, comparison, analysis of relationships, and study of cause-and-effect relationships.
Descriptive tasks are solved by simply collecting data using one of the methods suitable for a given situation - questioning, observation, document analysis, etc. One of the main tasks is to record data in such a way that in the future it will allow their aggregation.
To solve explanatory problems, a number of research approaches (for example, historical studies, case studies, experiments) are used to deal with the analysis of complex data. Their goal is not only to simply collect facts, but also to identify the meanings of a large set of social, political, cultural elements associated with the problem.
The general purpose of evaluation studies is to examine programs or projects regarding awareness, effectiveness, achievement of goals, etc. The results obtained are usually used to improve them, and sometimes simply to better understand the functioning of the programs and projects concerned.
Comparative research is used to gain a deeper understanding of the phenomenon being studied by identifying its common and distinctive features in different social groups. The largest of them are carried out in cross-cultural and cross-national contexts.
Research to establish relationships between variables is also called correlation research. The result of such studies is the production of specific descriptive information (for example, see pairwise linkage analysis). This is fundamentally quantitative research.
Establishing cause-and-effect relationships involves experimental research. In the social and behavioral sciences, there are several types of this type of research: randomized experiments, true experiments (involve the creation of special experimental conditions that simulate the necessary conditions), sociometry (of course, as Ya. Moreno understood it), garfinkeling.
Theoretical validation in sociological research: Methodology and methods
The very essence of research mixed type- These are exploratory designs. Having gone almost all the way through the “Training Materials”, you are ready to receive this lesson.
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Research design is a combination of requirements regarding the collection and analysis of data necessary to achieve the objectives of the study. If we talk about information technology, then the corresponding research designs relate, first of all, to the peculiarities of the combinatorics of elements of qualitative and quantitative approaches within the framework of one study.
The main principles of organizing designs in information technology are: 1) awareness of the theoretical drive (theoretical drive) research project; 2) awareness of the role of borrowed components in a research project; 3) compliance with the methodological assumptions of the basic method; 4) working with the maximum available number of data sets. The first principle has to do with the purpose of research (search vs confirmation), the appropriate types of scientific reasoning (induction vs deduction) and suitability in in this case methods. According to the second principle, the researcher should pay attention not only to basic strategies for collecting and analyzing data, but also to additional ones that could enrich the main part of the research project with data that is important and cannot be obtained using basic methods. The third principle is related to the need to adhere to the fundamental requirements of working with data of one type or another. The essence of the last principle is quite obvious and has to do with attracting data from all available relevant sources.
Often IST is “situated” on a continuum between qualitative and quantitative research (see Figure 4.1). So, in the presented figure, zone “A” indicates the use of exclusively qualitative methods, zone “B” - mainly qualitative, with some quantitative components, zone “C” - equal use of qualitative and quantitative methods (fully integrated research), zone “D” - mostly quantitative with some qualitative components, zone “E” - exclusively quantitative methods.
Rice. Qualitative-mixed-quantitative continuum
If we talk about specific IST designs, there are two main typologies. One is suitable for cases where qualitative and quantitative methods are used at different stages of the same study, the other for cases where alternating or parallel qualitative and quantitative studies are used within a research project.
The first typology includes six mixed-type designs (see Table 4.2). An example of a study that uses qualitative and quantitative methods at different stages is concept alignment. In this research strategy, data collection is done using qualitative methods (e.g., brainstorming or focus groups) and analysis is quantitative (cluster analysis and multidimensional scaling). Depending on the tasks being solved (search or descriptive), it can be classified as either the second or sixth design.
According to the second typology, nine mixed-type designs can be distinguished (see Table 3). This typology is based on two main principles. First, in a mixed-type study, it is important to determine the status of each of the paradigms - whether qualitative and quantitative research have the same status, or whether one of them is considered as the main one, and the second - subordinate. Secondly, it is important to determine how the research will be conducted - in parallel or sequentially. In the case of a sequential solution, it is also necessary to determine which of them is first and which is second in the time dimension. An example of a research project that fits this typology would be a case where the first phase is a qualitative study to build theory (for example, using Anselm Strauss' grounded theory), and the second is a quantitative survey of a specific group of people, to to which the developed theory is applicable and in relation to which it is necessary to formulate a forecast for the development of the corresponding social phenomenon or problem.
Table 1. Mixed research designs using qualitative and quantitative methods within the same study*
Objectives of the study |
Data collection |
Data analysis |
|
Qualitative goals |
Qualitative data collection |
||
Quantitative data collection |
|||
Qualitative data collection |
Conducting quantitative analysis |
||
Quantitative data collection |
Carrying out qualitative analysis |
||
Quantitative goals |
Qualitative data collection |
Conducting qualitative analysis |
|
Quantitative data collection |
Conducting quantitative analysis |
||
Qualitative data collection |
Conducting quantitative analysis |
||
Quantitative data collection |
Conducting qualitative analysis |
* in this table, designs 2-7 are mixed, design 1 is completely qualitative, design 8 is completely quantitative.
Table 2. Mixed-method research designs using qualitative and quantitative research as different phases of the same research project*
* “quality” means qualitative research, “quantity” means quantitative research; "+" - simultaneous research, "=>" - sequential; capital letters indicate the main status of the paradigm, small ones indicate the subordinate status.
Of course, these typologies do not limit the variety of research designs, and they should be considered as possible guidelines in IST planning.
IST designs in evaluation research.
According to the typology of IST designs used in assessment, two main types can be distinguished - component and integrative. In component design, although qualitative and quantitative methods are used within the same study, they are used separately from each other. In integrative design, on the other hand, methods belonging to different paradigms are used together.
The component type includes three types of designs: triangulation, complementary and expansive. In a triangulation design, results obtained from one method are used to confirm results obtained from other methods. In the case of complementary design, the results obtained using the main method are specified and refined on the basis of the results obtained using methods of secondary importance. When using an expansive design, different methods are used to obtain information regarding different aspects of the assessment, that is, each method is responsible for a specific piece of information.
The integrative type includes four types of designs: iterative, nested, holistic and transformational. In iterative design, the results obtained from a method suggest or guide the use of other methods that are relevant to the situation. Untested design deals with situations where one method is integrated into another. Holistic design involves the combined, integrated use of qualitative and quantitative methods to comprehensively evaluate a program. Moreover, both groups of methods have equivalent status. Transformational design occurs when different methods are used together to capture values that are subsequently used to reconfigure dialogue in which participants hold different ideological positions.
