Design of scientific research in medicine. Professor A.O.Gusan

What is a "clinical study"?

Clinical trial - a scientific study involving people, which is conducted to evaluate the efficacy and safety of a new drug or to expand the indications for the 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. In clinical trials, a new drug is being studied to obtain data on its efficacy and safety. Based on these data, the authorized health authority decides whether to register the drug or refuse registration. A drug that has not passed clinical trials cannot be registered and put on the 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 a general form, and sometimes it is impossible at all. For example, the pharmacokinetics (how a drug enters the bloodstream, is distributed in the body and excreted from it) in humans differs even from the pharmacokinetics in primates. However, the analysis of preclinical studies is very important for assessing the likelihood of development and nature side effects, calculation of the starting dose to study the properties of the drug in humans.

Clinical trials can only be initiated after encouraging results have been obtained in the course of preclinical studies (studies on biological models and laboratory animals), as well as the approval of the ethical committee and a positive decision by the authorized health authority of the country where the study is planned.

Initially, an experimental drug is studied in a small number of patients and/or healthy volunteers. As data on its safety and efficacy accumulate, the number of patients involved in the study increases, and the drug itself is compared with drugs already known and widely used in medical practice.

Types of clinical studies

The first way to classify clinical trials is by the presence of interference in the usual tactics of patient management, that is, in the standard procedures for examining and treating a patient.

An observational study is 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 way in accordance with the conditions set out in the marketing authorization. The issue of “assigning” a patient to a specific treatment strategy is not decided in advance in the study protocol. This issue is decided according to current practice, and the prescription of the drug is clearly separated from the decision to include the patient in the study. No other diagnostic or monitoring procedures are applied to patients, and epidemiological methods are used to analyze the collected data.

Interventional study - a study of new, unregistered medicinal products, immunobiological agents, medical equipment, or a study in which medicinal products, immunobiological agents, medical equipment are prescribed or applied in a way different from the conditions set forth in the registered instructions for use (whether it be a new indication, a new drug dosage, new route of administration, new route of administration, or new category of patients).

The criterion for another classification method is the purpose of the study. This classification method was proposed by the U.S. National Institutes of Health (NIH) and distinguishes six different types of clinical trials:

• Prevention trials are conducted to find the best ways to prevent diseases in people who have never suffered from them, or to prevent the recurrence of the disease in patients. These studies may include drugs, vaccines, vitamins, minerals, and lifestyle changes.
• Screening trials are conducted to find the best way to detect certain diseases or conditions.
• Diagnostic trials are conducted to find the best way to diagnose a particular disease or condition.
• Treatment trials are conducted to study the efficacy and safety of experimental drugs, new combinations of drugs, 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 who cannot be included in a clinical trial because they do not meet the inclusion criteria. Typically, such programs involve 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 Research Design

The study design is the overall design of the study, a description of how the study will be conducted.

The main types of observational studies are cohort and case-control studies, etc.

• In a cohort study, a selected group of people (cohort) is observed for some time. The condition of patients in different subgroups of this cohort, those who were or were not treated (or were treated to varying degrees) with the study drug, are compared. In a prospective cohort study, a study plan is first drawn up and the order of data collection and processing is determined, then cohorts are compiled, the study is conducted and the data are analyzed. In a retrospective cohort study, a cohort is selected from archival records and the health status of patients is tracked from the time the patient was followed up to the present.
• A case-control study compares people with a particular disease with people in the same population who do not have the disease in order 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 (one-shot epidemiological study), etc.

The reference design for clinical trials is randomized, controlled, double-blind trials.

The randomization procedure means that patients are assigned to treatment groups at random and have the same chance of receiving the study or control drug. The course of treatment prescribed to the patient usually has an effect, regardless of whether he receives an 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 an active principle, which completely imitates the study drug in shape, color, taste, smell. If an active method of treatment is used for control, then the studied drug is compared with the therapy already known and widely used today (the so-called "gold standard").

Giving patients in the control group a placebo raises some ethical concerns, as it may limit their right to receive the best treatment currently available. Placebo options are limited. The Declaration of Helsinki of the World Medical Association (WMA) specifies that a placebo is used in only two cases:

• first, if effective way there is no cure for the disease
• secondly, if there are compelling scientifically sound methodological reasons for using a placebo to assess the efficacy or safety of a drug, and patients receiving placebo or no treatment will not be at risk of causing serious or irreversible damage to their health.

Psychological or so-called subjective factors are of great importance in clinical trials. For example, the patient's knowledge that he is receiving therapy with an active drug may affect the assessment of the safety and efficacy of therapy. A research physician who is convinced of the benefits of one of the compared drugs may unwittingly interpret improvements in the health of patients in its favor or try to prescribe a treatment that he considers more effective for a patient with a more severe disease. To minimize the influence of subjective factors, a blind method of research is used.

A study in which the patient does not know and the researcher knows what treatment the patient is receiving is called simple blind. If neither the patient nor the researcher knows about the prescribed treatment, such a study is called double-blind.

Blind studies allow you to minimize the possibility of intentional distortions, and unintentional - to distribute between groups in equal proportions.

Clinical study protocol

A protocol is a document that describes the purpose, objectives, design, methodology, statistical aspects, and organization of a study. Any clinical trial begins with the development of a protocol. It is the most important document of a clinical trial.

Having studied the protocol, the authorized health authorities and ethical committees evaluate the adequacy of the set scientific tasks 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 investigators. It allows you to unify the work of research centers around the world. After the end 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 of a large study can be developed over several years, 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 that is signed by the participants in the study (patient and research physician). The research physician informs the patient about all aspects of the clinical trial that may affect the decision to take part in the experiment (benefit, risks, time costs, possible side effects, etc.). Therefore, such consent is called informed. After all aspects of participation in a clinical trial are explained to a potential research participant, the investigator provides the patient with written information that describes the details of the study (duration, procedures, risks, potential benefits, etc.). Once again carefully studying the document, the participant decides whether he should sign the consent or not.

A participant in the study can withdraw from the study at any time without giving reasons.

Research Power

When planning a clinical trial, the sponsoring company, with the help of biomedical statisticians, determines how many patients need to be enrolled in the trial in order to obtain a statistically significant result showing the difference in the effectiveness of the 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 sponsor company decides on the appropriateness of the study.

The number of patients required to obtain a statistically significant result depends on the disease, parameters studied, 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, far fewer patients are needed than in a placebo-controlled study of a well-cured ovarian cancer. The fact is that if the patient can recover without treatment, then spontaneous cases of improvement will “obscure” the effect of therapy. In order to single out exactly the part of patients who were helped by 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 without treatment immediately deteriorates sharply, then the effect of therapy will be visible in a small group - the health status of those who receive effective treatment will not deteriorate immediately.

The characteristic of a study that reveals clinically important differences between the investigational product and the comparator product (eg, in efficacy), if any, actually exists, 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 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 no longer have clinical significance. Therefore, a distinction is made between statistical and clinical significance.

Phases of clinical trials

Preclinical studies include in vitro studies ( laboratory research in vitro) and in vivo studies (studies in laboratory animals) in which various doses of a test substance are examined to provide preliminary data on the pharmacological properties, toxicity, pharmacokinetics and metabolism of the study drug. Preclinical studies help pharmaceutical companies understand whether a substance is worth investigating further. Human studies may be initiated if evidence from preclinical studies indicates that the drug can be used to treat the disease, if the drug is sufficiently safe and the studies do not put people at unnecessary risk.

The drug development process is often described as a sequence 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 the 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 the high toxicity of the drug (for example, for the treatment of cancer and AIDS) makes 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 that have the necessary equipment and specially trained staff. Phase I trials may be open-label and may also use baseline controls. 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.

During phase I, indicators such as absorption, distribution, metabolism, excretion, as well as the preferred form of application and a safe dosage level are investigated. Phase I usually lasts from a few weeks to 1 year.

Remuneration is paid for participation in the study.

There is different types phase I studies:

Single Ascending Dose studies (SAD) are studies in which a small number of patients receive a single dose of an investigational drug for as long as they are under observation. If no adverse reactions are detected and the pharmacokinetic data corresponds 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 the pre-targeted levels of pharmacokinetic safety are reached or unacceptable adverse reactions are detected (they say that the maximum allowable dose has been reached).

Multiple Ascending Dose studies (MAD) are studies that are conducted to better understand the pharmacokinetics and pharmacodynamics of a drug with repeated administration. During such studies, a group of patients receive low doses of the drug repeatedly. After each injection, blood and other bodily fluids are taken to evaluate how the drug behaves in the human body. The dose is gradually increased in the following groups of volunteers - up to a predetermined level.

Phase II

Having assessed the pharmacokinetics and pharmacodynamics, as well as the preliminary safety of the investigational product during phase I studies, the sponsor company initiates phase II studies in a larger population (100-500 people).

Phase II studies can be designed in a variety of ways, including controlled studies and baseline studies. Follow-up studies are usually conducted as randomized controlled trials to evaluate the safety and efficacy of a drug in a given indication. Phase II studies are usually conducted on a small homogeneous patient population selected according to strict criteria.

An important goal of these studies is to determine the dosage level and dosing regimen for phase III studies. The doses patients receive in Phase II trials are usually (though not always) lower than the highest doses administered to participants during Phase I. An additional challenge in Phase II trials is to evaluate potential endpoints, the therapeutic regimen ( including concomitant drugs) and target grouping (eg, mild versus severe) for further studies during Phase II or III.

Sometimes phase II is divided into phase IIA and phase IIB.

Phase IIA are pilot studies designed to determine the 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 different doses of the drug, depending on the characteristics of the patient group, frequency of administration, dose, etc.

Phase IIB are well-regulated studies designed to determine the efficacy and safety of a drug in patients with a specific disease. The main task of this phase is to determine the optimal dosing level for phase III.

Some phase I and II studies are combined so that both the efficacy and safety of the drug are tested.

In phase II, a control group is mandatory, which does not differ in composition and number of patients from the group receiving the study drug. Patients in the two groups should be matched in terms of sex, age, and prior background treatment. At the same time, the efficacy 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 trials are randomized, controlled, multicentre trials with a large patient population (300-3,000 or more, depending on the disease). These studies are designed to confirm the safety and efficacy of a drug previously assessed during phase II for a specific indication in a specific population. Phase III studies may also investigate the dose-response effect of a drug or drug when used in a wider population, in patients with disease of varying severity, or in combination with other drugs.

Sometimes phase III trials continue when registrations have already been filed with the appropriate regulatory authority. In this case, patients continue to receive the life-saving drug until it is registered and available for 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 registered indications, but also for other indications or in other groups of patients, as well as to obtain additional information about security). Studies of this kind are sometimes classified as phase IIIB.

Having confirmed the efficacy and safety of the drug in the course of phase III studies, the company forms the so-called registration dossier of the drug, which describes the methodology and results of preclinical and clinical studies of the drug, production features, its composition, expiration date. The totality of this information is the so-called "registration dossier", which is submitted to the authorized health authority that performs registration (each country has its own).

the drug is more effective than known drugs of similar action,

has better tolerability compared with already known drugs,

effective in cases where treatment with already known drugs is unsuccessful,

economically more 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 research. These are studies conducted after registration of the drug in accordance with the approved indications. These are studies that were not required for registration of the drug, but are necessary to optimize its use. The requirement to conduct these studies may come from both regulatory authorities and the sponsoring company. The purpose of these studies may be, for example, to conquer 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 to collect additional information on the safety of the drug in a sufficiently large population for a long time.

Also among the goals of phase IV may be the evaluation of such parameters of treatment as the timing of treatment, interactions with other drugs or foods, a comparative analysis of standard treatments, analysis of the use in patients of various age groups, economic indicators of treatment and long-term results of treatment (decrease 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 according to the registered indication, but the scheme of examination and patient management is determined by the study protocol and may differ from routine practice), after the approval of the use of the drug in the country, post-registration observational (non-interventional) studies can be conducted. 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 rare but dangerous side effects are found during phase IV studies or post-registration observational studies, the drug may be withdrawn from the market, its use may also be limited.

Phase division is a common but approximate way of classifying clinical trials because the same trial can be conducted in different phases. For example, although pharmacological studies are usually conducted during Phase I, many of them are initiated in each of the three phases, but are still sometimes referred to as Phase I studies. is an adjustment to the entire research plan. For example, the results of a confirmatory therapeutic study may require additional human pharmacological studies.

Therefore, the most preferred classification criterion is the purpose of the study.

SCIENTIFIC RESEARCH IN SOCIOLOGY, ITS ORGANIZATION

Every exploration begins with a basic question: why things are the way we observe them. We are looking for an explanation for the phenomena we observe. Where to begin?

First of all, with search for the necessary literature. If we are lucky, this search leads to a ready-made explanation in the form of a theory - a theory formulated by someone who has observed similar phenomena before us. More often than not, we have to use literature in a more creative way, trying to construct the most appropriate possible explanation. The rest of the research process is then devoted to testing this explanation: in order to understand how much it contributes to our understanding - understanding the essence of the phenomenon under study.

The first step in this process verification our theories consists in the formulation of some hypotheses, which, from a logical point of view, must correspond to reality - if our initial assumptions regarding the essence of the observed phenomenon are observed. These – working – hypotheses serve for the following:

- they determine the variables that will appear in our study;

- they dictate the ways and methods of organizing research in the most optimal way, in terms of obtaining irrefutable evidence of the correctness of our understanding.

If our theory is a prototype building, then a separate working hypothesis is element this building. Necessary brick of this particular building the theory we use. The working hypothesis explains one of the possible connections that form - in a complex - the process we are studying.

When formulating a hypothesis, it is necessary to be aware of whether it is practically possible to observe the connection of phenomena explained by it. Will we be able to find the data we need, do we have the opportunity to do so? It seems essential that the researcher select hypotheses that can be adequately tested, taking into account the time, resources and abilities of the researcher himself. Otherwise, we will fail.

Then the variables used in the study should be operationalized in such a way that we can work with them, and that as a result we can draw conclusions that are significant for our study. Here again, the question of resources arises - if we do not have the time, money necessary for measurements, assistance (from, say, persons participating in the survey public opinion), - there is no point in getting to work. In addition, it is necessary to ask oneself the question: is there a substitution of concepts in the process of research in connection with the use of an unacceptable method? The scientific value of a method must be very carefully considered before we start collecting data, for no matter how carefully they are collected, the inadequacy of the research method can invalidate the results of the study.

In developing the method of our research, we must also think about the future analysis of the collected data. The researcher must determine, based on the working hypothesis he has accepted, what specific mathematical and statistical comparisons will be needed to test it. The main problem here is to find correct ratio between the level of measurement resulting from accepted operationalization of variables, and the level of measurement adopted in those standard statistical procedures that will be used in research; that is, the data obtained at the time of collection must be suitable for use in the statistical processing process. You need to make sure that they are not only the same data that are usually used in these procedures, but also accurate enough to be processed. The distribution of the received data must also correspond to the standard statistical distribution - otherwise it will be difficult to process them.

The next step is to design, designing our study in such a way that the measurement procedure, data collection was applied with the greatest efficiency. The main task of design is to make sure, to be completely sure, that the connection between the phenomena that we observe is explained by our working hypothesis, and is not a random phenomenon or the product of a completely different system of relationships. Alternative working hypotheses must be rejected - and not without evidence, but on the basis of serious analysis. Therefore, good design begins, first of all, with a review of the literature relevant to our field of study. This literary review, the review - together with a logical analysis of the situation - should have the aim of rejecting other possible working hypotheses even before we give place to our own explanation of the observed phenomena.

Exploratory design should be developed through:

1) identification of comparisons used in testing the working hypothesis;

2) determining what kind of observations should be carried out (whom or what, in what order, by what means, under what conditions);

3) determining the place of the data collected during the comparative study (no connection, positive connection, negative connection, etc.);

4) determining the main competing hypotheses that also claim to explain the possible outcome of the study, and

5) organizing a set of observations in such a way that additional comparisons (testing the applicability of the main competing hypotheses) are carried out (regardless of the actual results of the study).

When choosing the design of our study, it is necessary to know which statistical methods of analysis it is desirable to apply, because. design determines the nature of the collected data. In the process of designing our study, as well as in choosing a hypothesis and choosing a method, it is absolutely necessary to ask ourselves if the task we have set is not impossible given the resources, time and our abilities that we have. The best design won't do anything if we don't have the ability to implement it. Therefore, one should be careful about the cost and logic of the data collection process in the process of designing a study.

DATA COLLECTION AND ANALYSIS

As mentioned above, the collection of data and their analysis are aimed at checking the compliance of the working hypothesis with reality. Here it is necessary to note the following.

Various methods of data collection can be applied both individually and in combination. Miscellaneous Methods serve different purposes. A researcher may, for example, engage in direct observation of a certain political group in order to collect information of a general nature in order to develop a working hypothesis, come to some preliminary conclusions, and then, in order to obtain accurate data, test this hypothesis, resort to a survey. . Besides, the use of several methods in one study increases the scientific value of its result. For example, in a study of variations in the quality of public services in the vicinity of a city, one may find it desirable to corroborate the results obtained by public opinion polling with statistics, official documents, interviews with officials, and the judgments of professionally trained observers. If all these methods of data collection lead to the same results regarding the relative position of each of these areas on the quality of service scale, the researcher can be sure of their applicability to the task at hand.

empirical research may take on the character of discovery. Instead of testing hypotheses that stem from the explanations accepted by the researcher, he can collect data that give rise to fundamentally new interpretations - usually each study raises new questions, suggests new explanations, and leads to new studies.

DETERMINING THE SCIENTIFIC VALUE OF RESEARCH

In designing your own or evaluating someone else's research, it is important to be able to assess whether it meets the general but well-defined criteria of objective value. The list below is quite extensive and a single study may contain some minor technical inaccuracies. But if the researcher can answer these questions in the affirmative (at least in the main), he can be sure that his project is free from fundamental errors that annul the significance of the work done.

1. Is the question to be answered correctly formulated? Do we know the objectives of the study in their entirety? Is the research related to a more fundamental question or problem? Is the object of study important?

2. Are the main objects of analysis correctly selected, clearly identified and consistently applied?

3. Are the concepts on which the study is based clearly articulated and adequately used? Where are they taken from?

4. Is it clear which explanations need to be tested? If a theory is used, is it logically correct? Where is the source of the theory and its constituent explanations?

5. Is the theory or explanation consistent with existing literature on the subject? Has the literature been researched in detail? Does the project relate to previous research or to more principled research questions?

6. Are working hypotheses clearly identified and formulated? Do they follow logically from the explanation or theory being tested? Are they subject to empirical testing?

7. If more than one hypothesis is being tested, what is the relationship between them? Are all hypotheses relevant to the theory, is their role in testing the theory obvious?

8. Are all variables clearly defined and their status (dependent or independent) stated in the working hypothesis?

9. Are variables included in the study that could modify the proposed relationship?

10. Are the concepts clearly operationalized? Are measurement procedures detailed so that others can use them? Have they been used by other researchers?

11. Can these procedures be relied upon as fully appropriate for the object of analysis? Have they been verified for this?

12. Is the design of the study clearly defined, does it correspond to the task set - testing the working hypothesis? Are alternative competing hypotheses taken into account and are the conditions created during the project design to test them in light of possible alternative explanations? Is there a logically coherent basis for the relationships to be identified?

13. Is the “population” of interest to the researcher defined correctly? Is the sample representative? If not, is the researcher aware of the limitations this places on their results? Is the sampling procedure adequately explained?

14. Is the data collection technique (survey, content analysis, etc.) appropriate for the purpose of the study with its objects of study and the type of information collected? Have all the rules of this method of collecting information been followed?

15. Is the data collection process clearly presented? Are their sources fully identified and can others identify them?

16. Is the coding system chosen fully defined and justified (such as the reduction of certain income groups to more general categories, or the treatment of “support” or “against” responses?).

17. Is the design of the scales or indices used in the study explained? Are they one-dimensional? Does their use preserve the original meaning of the concepts?

18. Have the tools been checked?

19. Have there been attempts to verify the results with other sources?

20. Is the graphic design appropriate for the nature of the data collected? Is it noted in the text? Do the tables and graphs distort the results?

21. Are these graphs and tables easy to interpret?

22. Is the proposed interpretation correct?

23. Is the statistical method of data processing chosen correctly? Is it suitable for summing them up in tables and graphs?

24. When investigating the relationship between variables, does the researcher provide data on their strength, direction, shape and meaning?

26. Does the level of statistics used correspond to the level of the selected variables, as well as the purpose of the study?

27. Do the obtained data correspond to the possibilities of the method and how is it shown by the researcher?

28. Does the researcher confuse the concepts of statistical and substantive significance of the results obtained? Does he use them one instead of the other?

29. Have alternative hypotheses been statistically investigated, and have the results of this study been presented and interpreted correctly?

30. Does each stage of data analysis relate to the main conclusion of the study? Are the proposed interpretations consistent with the underlying theory or explanation?

31. Does the study report contain:

a) a clear statement of the objectives of the study;

b) a necessary review of the literature to demonstrate the place of research in the general context of this direction in science;

c) an adequate explanation of the design, data and research methods;

d) a clear statement of conclusions?

32. Are the conclusions reached supported by the data presented and the choice of study design? Does it represent a serious contribution to the literature on the problem, or does it seem too general?

It must be emphasized that the above criteria for the scientific value of research have a very wide scope - they are by no means tied to sociology - they are universal.

Topics for abstracts

1. The program of political sociological research is the addition of new knowledge to the existing one.

2. Hypothesis - the locomotive of political and sociological research.

3. Types of sociological research - how many can there be?

4. Interpretation of basic concepts - what method of philosophical knowledge is similar to this interpretation?

5. Problematic situation, its significance in the program of political and sociological research.

Questions and tasks for repetition

1. Where does any serious research begin? Why?

2. What role does theory play in research? What is the ratio between theory and working hypothesis?

3. What dictates the choice methodology research? Isn't he random? Justify.

4. Why does the use of several methods in one study increase its value? Give examples.

5. What is study design? What should be guided by when choosing a design?

6. What does the term mean correctness of the study? How is it defined?

7. What numerical methods are used in applied sociology? What is the criterion for their selection?

8. What is the difference between statistical and substantive the significance of the result?

9. What kind ethical problems can arise in the course of sociological research and how should they be resolved?

• evidence-based medicine

• Medical Research Design

• Pivina L.M., PhD, assistant

• Department of Internal Diseases № 2

Previous events

• Reducing infant mortality and rapid population growth

• Change in the structure of morbidity from acute diseases to the predominance of chronic

• Changing the etiological nature of diseases - from infectious agents to behavioral factors

• The rapid development of medical science and the growth of medical technology

• Development of social insurance systems

What does evidence-based medicine mean?

• “…conscientious, accurate and meaningful use of the best results of clinical research to make decisions in the care of a particular patient.”

• (Sackett D., Richardson W., Rosenberg W., Haynes R. Evidence-based medicine. How to practice and teach EBM. Churchill Livingstone, 1997.)

The concept of evidence-based medicine

• The purpose of the concept of evidence-based medicine is to give doctors the opportunity to find and use evidence-based facts obtained in the course of correctly conducted clinical trials in making clinical decisions, to increase the accuracy of predicting the outcomes of medical interventions.

• The concept is based on two main ideas:

• Every clinical decision of a physician must be based on scientific evidence.

• The weight of each fact is the greater, the stricter the methodology of scientific research, during which it was obtained.

• Fingers M.A. 2006

When did evidence-based medicine appear?

• 1940 - First randomized trials (use of streptomycin in tuberculosis)

• 1960 thalidomide tragedy

• 1962 - The US Food and Drug Administration introduced regulations requiring controlled trials of new drugs.

• 1971 - Cochran raised the issue of lack of scientific evidence

• 1980-90 - Drawing attention to the need to include systematic reviews in clinical guidelines

• 1994 - First Cochrane colloquium at Oxford

• 1994 - EBM term

• 1996 - most British doctors already know the term EBM

• 1996 - The British Minister of Health declared that his main task was to promote the concept of EBM

• 1996 EBM headlines in leading British newspapers

• 1999 - BMJ publishes EBM handbook (US circulation ½ million)

• 2001 - German, Spanish, Russian, Japanese editions

• DM was named after Archie Cochrane, an English epidemiologist, who pointed out the need to evaluate the role of a particular clinical intervention using controlled clinical trials and store the results in a special database on the effectiveness of medical care.

• He was the first to formulate the concept of evidence-based medicine.

• Research has shown that

• for 2/3 patients doctors

• need information, but

• receive it only in

• a small number of cases. Where to get the necessary information?

• Observations show that in some domestic journals up to ½ of the articles are of an advertising nature in terms of content, design, or are associated with print advertising.

To keep up with the times…….

• “… a doctor needs to read 10 journals, approximately 70 original abstract articles per month….”

• Sackett D.L. (1985)

• "... you need to read 15 articles 365 days a year ..."

• McCrory D.C. (2002)

• Less than 1 hour per week available to practitioner for reading

Relationship between practitioner and medical information

• Information boom

• Difficulties in finding reliable ("evidence") information

• Difficulties in analyzing information

• Difficulties in making effective clinical decisions

• medical errors

• Appointment of unreasonable interventions

Justification for the need for regulation

• In the US, 98,000 deaths per year from medical errors (IOM, 2000)

• Only 30% of medical interventions with reliably proven effectiveness

• Ineffective (and sometimes harmful) interventions are widespread

• Interventions with proven effectiveness are far from being received by all those in need

• The use of cocarboxylase, riboxin, asparkam

• Parenteral administration of vitamins as an adjuvant treatment

• Appointment of angioprotectors, absorbable drugs

• Prophylactic administration of iron and folic acid to pregnant women– positive impact on maternal and newborn health

• Mammography for early detection of breast cancer

Effect of rehabilitation training programs on CAD outcomes in patients with myocardial infarction over 3 years of rehabilitation (meta-analysis)

Components of quality medical care (Haynes et al'96)

Clinical epidemiology

• DM is based on clinical epidemiology which is a branch of medicine that uses the epidemiological method to obtain medical information based only on strictly proven scientific facts, excluding the influence of systematic and random errors.

Feelings that scientific research evokes in us

FraminghamHeartStudy ( Framingham Study ) Massachusetts, under the auspices Heart, Lungand Blood

FraminghamHeartStudy ( Framingham Study ) a typical example of clinical epidemiology. This study began in 1948 to investigate cardiovascular health in Framingham, Massachusetts, under the auspices National Heart Institute (later renamed National Heart, Lung and Blood Institute: NationalHeart, Lungand Blood Institute; NHLBI). Initially, the study covered 5209 men and women. In 1971, it included 5124 representatives of the second generation of participants - “offspring”. Now the researchers are planning to start a survey of 3,500 grandchildren of those who entered the study more than 50 years ago - the "third generation". The study is unparalleled in terms of the duration and size of the cohort, and its significance for modern medicine, and primarily cardiology, can hardly be overestimated. Over the years of careful monitoring of study participants, the main risk factors leading to diseases of the cardiovascular system have been identified: high blood pressure, elevated blood cholesterol, smoking, obesity, diabetes, etc. Since its inception, the results of the study have been published in about 1,200 articles in the world's major medical journals.

• Deviation from the norm Healthy or sick

• Diagnosis How accurate are the methods

• Frequency How common is the condition

• Risk What factors are associated with an increased risk of the disease

• Prognosis What are the consequences of the disease

• Treatment How will the course of the disease change with treatment?

• Prevention Are there methods to prevent disease in healthy people? Does the course of the disease improve with early recognition and treatment?

• Cause What factors lead to the disease?

• Cost How much does this treatment cost?

• diseases?

Frequency

• Frequency

• Risk

• Forecast

• Treatment

• Prevention

• Cause

retrospective

• retrospective(retrospective study) - past events are evaluated (for example, according to medical records)

• prospective(prospective study) - first, a research plan is drawn up, the procedure for collecting and processing data is established, and then a study is conducted according to this plan.

Classification of research by design

• 1. Observational studies (studies - observations)

• one or more groups of patients are described and observed for certain characteristics

• 2. Experimental studies

• the results of the intervention are evaluated (drug, procedure, treatment, etc.), one, two or more groups participate. The subject of research is observed

Classification of scientific clinical trials

Research structure

• By time:

• Cross-sectional studies

• Longitudinal studies

Longitudinal Research

Description of cases

• Descriptive reviews- the most "readable" scientific publications that reflect the author's position on a specific issue

• Most often present the medical history of one patient

• One way to comprehend complex clinical situations

• But no scientific proof

Series of clinical cases and clinical cases

Types of observational studies Case series or descriptive studies

• A case series description is a study of the same intervention in individual consecutively included patients without a control group.

• For example, a vascular surgeon may describe the results of carotid revascularization in 100 patients with cerebral ischemia.

Types of observational studies Case series or descriptive studies, features

• describes a certain number of characteristics of interest in observed small groups of patients

• relatively short study period

• does not include any research hypotheses

• has no control groups

• precedes other studies

• this type of study is limited to data on individual patients

Study case - control (case control study)

• A study that is designed to compare two groups of participants with developed and non-developed clinical outcomes (usually poor) in order to identify differences in the influence of certain risk factors on the development of this clinical outcome.

• This study design is most useful when trying to determine the cause of rare diseases, such as the development of CNS disorders in children after pertussis vaccine.

Occasions:

• Occasions: the presence of a disease or outcome

• Control: no disease or outcome

• Possible causes or risk factors for the disease are assessed retrospectively, but this is not a historical control

• Answers the question "What happened?"

• Longitudinal or longitudinal study

Case-control studies

• Design

Advantages and disadvantages

• Advantages

• Best Design for rare diseases or conditions requiring long periods of time
• Used to test primary hypotheses
• Very short term
• Least Expensive

• Flaws

• A large number of biases and systematic errors
• Depends on the quality of primary descriptions and measurements
• Difficulties in selecting an appropriate control group

• A study that is designed to follow a group (cohort) of participants and identify differences in their rates of certain clinical outcomes.

• A group of patients is selected for a similar sign, which will be traced in the future

• Begins with an assumption of a risk factor or outcome

• Exposed to RF and Unexposed

• Prospective in time, determination of the desired factors in the exposed group

• Answers the question "Will people get sick if they are exposed to a risk factor?"

• Mostly prospective, but there are also historical cohort (retrospective)

Design

• Design

Advantages and disadvantages of cohort trials

• Advantages

• The best design for studying the causes of conditions, diseases, risk factors and outcomes.
• Enough time to obtain rigorous evidence
• Many systematic errors can be avoided (occur if the outcome is known in advance)
• Evaluates the relationship between exposure to a risk factor and several diseases

• Flaws

• Longitudinal
• Expensive (research more of people)
• Evaluates the relationship between disease and exposure to a relatively small number of factors (those identified at the start of the study)
• Cannot be used for rare diseases (sample size must be larger than the number of individuals with the disease under study)

Types of observational (descriptive) studies Cross-sectional study (prevalence)

• Data is collected at a specific point in time

• Types:

• Prevalence of disease or outcome
• Studying the course of the disease, staging

• Answer the question "How much?"

Prevalence studies

• Design

TERMINOLOGY

• Prevalence- prevalence. Example: CHD prevalence in a population number of people with CHD/total population as a percentage.

• Incident- primary morbidity. Example: asthma incident in children in Semey = number of new cases of asthma in children in Semey / number of children living in Semey.

• The higher the incidence (I) and the longer the disease or condition, the higher the prevalence (P)

• P = I x L

RANDOMIZED CONTROLLED TEST (RCT) (Controlled Clinical Trials, CCT)

• - THE GOLD STANDARD FOR ANY DIAGNOSIS AND TREATMENT METHOD.

• Typically, this is a study in which participants are randomly assigned (randomized) into two groups - the main group (where the intervention under study is used) and the control group (where a placebo or other intervention is used. This design of the study allows you to compare the effectiveness of interventions.

Scheme of a typical RCT

Design

• Design

placebo control

• placebo control

• Active treatment

• Comparative characteristics of doses

Flaws

• Flaws

• often takes a long time
• Very expensive
• Not suitable for rare diseases
• Limited generalizability

• Advantages

• the best data for patients
• less bias (systematic error)
• best for evaluating effectiveness and validating interventions
• If randomized, most rigorous in design and valid

Development of the Study Protocol

• The protocol (program) of a clinical trial is a document that contains instructions for everyone who takes part in a clinical trial, with specific tasks for each participant and instructions for completing these tasks.

• The protocol provides qualified research, as well as the collection and analysis of data, which are then submitted for review to the authorities of the control and licensing system.

Development of an Individual Registration Card

• The Individual Registration Card (CRC) is a means of collecting data from a paper-based study conducted at a study center. Some studies also use electronic means for this purpose.

• In the first phase (Phase 1) of a clinical trial, researchers study a new drug or treatment in a small group of people (20-80 people) to first determine its safety, establish a safe dose range, and identify side effects.

• In the second phase (Phase II), the study drug or treatment is given to a larger group of people (100-300 people) to see if it is effective and to further test its safety.

Stages (phases) of a clinical trial

At the third stage (Phase III), the study drug or treatment method is prescribed to even larger groups of people (1000-3000 people) to confirm the effectiveness and safety, control side effects, as well as to compare with commonly used drugs and treatments, to accumulate information that will allow it is safe to use this medicine or treatment.

The fourth stage (IV phase) of research is carried out after the drug or treatment method has been approved for use by the Ministry of Health of the Republic of Kazakhstan. These studies continue testing the study drug or treatment to further gather information about its effects on different groups of people and identify any side effects that appear with long-term use.

• A review is a solid scientific study that clearly articulates the question under study, describes in detail the methods used to search, select, evaluate and synthesize the results of various studies relevant to the question under study. A systematic analysis may include meta-analysis (but its use is optional).

Meta-analysis (meta-analysis)

• Summarizing the results of several studies on the same topic

It is mainly compiled on the basis of systematic reviews. A method of statistical analysis that combines the results of several studies and presents the final score as a single weighted score (with more weight usually given to large studies or studies of higher methodological quality).

Medical Research Design Conclusions

• RCT– maximum strength, but often expensive and time-consuming

• well prepared observational studies give good results in identifying the causes of diseases, but not enough evidence

• Cohort studies–best for studying the course of diseases and identifying risk factors

• Case-control studies fast and cheap

Choice of research methodology

• Quantitative research: designed to answer the questions: “How much” and “How much?” Aimed at identifying relationships, usually causal relationships between variables.

• Collection of information on the problem of interest and mathematical analysis of the obtained quantitative data.

• The goal is to identify general patterns that are characteristic not only for the surveyed group of people, but for the entire population as a whole, which will allow the researcher to interpret the problem and make predictions.

Qualitative Research

• It is designed to answer the questions: “Who? Why? When? and where?" and aimed at a deeper study of the problem.

• The problem is considered from different points of view.

• The purpose of the study is to reveal the principles (patterns) characteristic of the studied population, according to which the phenomena of interest to us proceed and which will allow us to give a deeper understanding of the problem.

Qualitative Research

Data collection methods:

• quantitative

• Tests and various measurement methods

• Questionnaires, questionnaires

• Formalized data collection

• Important elements are:

• Presence of a control group
• Randomization

Data analysis

• quantitative

• Statistics

Reliability of evidence

Clinical Research 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. Consider three common design options:

Clinical study in one group (single group design)

Clinical study in parallel groups (parallel group design)

Clinical study in a crossover group design

Clinical study in one group

(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. Thus, subjects are not randomized to treatment groups.

The single-group clinical trial model can be illustrated as follows:

Screening -- Inclusion -- Baseline -- Treatment -- Outcomes

The single group model can be used in Phase I studies. Single-arm study models are generally not used in Phase III clinical trials.

The main disadvantage of the single-arm study model is the lack of a comparison group. The effects of experimental treatment cannot be differentiated from the effects of other variables.

Clinical study in parallel groups

(parallel group design)

When conducting clinical trials in parallel groups, the subjects of two or more groups receive different therapy. To achieve statistical significance (to eliminate systematic errors), the subjects are divided into groups by the method of 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 are different drugs or different doses or placebo

Clinical trials in parallel group design are costly, time consuming, and require a large number of subjects (with a low event rate). However, clinical studies in parallel groups are the most objective in determining the effectiveness of treatment and accurate in formulating conclusions. Most clinical trials are thus conducted in parallel group design.

Sometimes studies in parallel groups can be used in two versions - these are factorial and heterogeneous models.

factorial design-- this is a design based on several (more than 2) parallel groups. Such studies are performed when a combination of different drugs (or different doses of the same drug) needs to be studied.

The factorial model of clinical research can be illustrated as follows:

Screening -- Inclusion -- Run-up -- 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 combination drugs.

The disadvantage of the factorial model is the need to involve a large number of subjects and, as a result, an increase in the cost of research.

Withdrawal (Discontinuation) Design

A heterogeneous model is a variant of parallel-group studies where all subjects are initially treated with experimental treatment, then patients with appropriate reactions are randomized into groups using double-blind or placebo technology to continue experimental treatment. This model is usually used to assess the effectiveness of experimental treatment by discontinuing the drug immediately after the onset of the reaction and registering relapse or remission. On fig. 5 is a diagram of a heterogeneous research model.

Screening - Inclusion - Experimental treatment - Treatment response - Randomization of responders - Treatment or placebo

A heterogeneous design of studies is particularly effective for the evaluation of medicines intended for the treatment of intractable diseases. In such studies, only a small percentage of subjects show responses 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 response to placebo. In addition, heterogeneous models are used to study relapses.

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 patients to stabilize and the effect to be more clearly identified. medicinal product. It should be noted that the percentage of subjects excluded from these studies can be high.

Ethical considerations require careful consideration of the use of this research design, as it may require the drug to be excluded from therapy if it provides relief to patients. Rigorous monitoring and clear definition of endpoint indicators are of paramount importance.

"Cross" model

(Crossover Design)

Unlike parallel-group study designs, cross-sectional models allow the effects of both study drugs and comparative treatments to be assessed in the same subjects. The subjects are randomized into groups in which the same course of treatment is carried out, but with a different sequence. As a rule, a "washout" period is necessary between courses in order for the indicators in patients to return to baseline, and also in order to exclude the undesirable influence of the residual effects of the previous treatment on the effects of the subsequent one. A "washout" period is not necessary if the analyzes of individual reactions of the subject are limited to their comparison at the end of each course, and the treatment period lasts long enough. Some crossover models use pre-crossover, which means that patients who are excluded from studies at the treatment stage can be transferred to alternative treatment groups earlier than planned.

Screening - Preparation period - Condition control - 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

"Cross-over" models are commonly used to study pharmacokinetics and pharmacodynamics when the goal is to control 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 in pharmacokinetic and pharmacodynamic studies with a sufficient "washout" period.

"Crossover" models are more economical than parallel group models because they require fewer subjects. However, sometimes there are difficulties in interpreting the results. The effects of one therapy can be mixed with the effects of the next. It can be difficult to distinguish the effects of sequential treatments from the effects of individual courses. In clinical trials, the crossover model usually takes longer than parallel group studies because each patient goes through at least two treatment periods plus a washout period. This model also requires more characteristics for each patient.

If the clinical conditions are relatively constant throughout the duration of the study, then the "cross-over" model is effective and reliable.

Relatively low sample size requirements make cross-sectional models useful in early clinical development in order to facilitate decisions on larger parallel study models. Because all subjects receive the study drug, cross-over studies are also effective for assessing safety.

Theoretical Validation in Sociological Research: Methodology and Methods

The very essence of mixed research is research designs. Going almost all the way" teaching materials"You're ready for that lesson too.

0 Click if it's useful =ъ

Research design is a combination of data collection and analysis requirements necessary to achieve research objectives. If we talk about ICT, then the corresponding research designs are related, first of all, to the peculiarities of the combinatorics of the elements of qualitative and quantitative approaches within the framework of one study.
The main principles of design organization in ICT are: 1) awareness of the theoretical drive of the research project; 2) awareness of the role of borrowed components in a research project; 3) compliance with the methodological assumptions of the base method; 4) work with the maximum available number of data sets. The first principle has to do with the purpose of the inquiry (search vs. confirmation), the appropriate types of scientific reasoning (induction vs. deduction), and the appropriate methods. According to the second principle, the researcher should pay attention not only to the main data collection and analysis strategies, but also to additional ones that could enrich the main part of the research project with data that are important and cannot be obtained using the main 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 is related to the attraction of data from all available relevant sources.
Often ICTs are “placed” on a continuum between qualitative and quantitative research (see Figure 4.1). So, in the presented figure, zone "A" denotes the use of exclusively qualitative methods, zone "B" - mostly qualitative, with some quantitative components, zone "C" - the equivalent use of qualitative and quantitative methods (fully integrated studies), zone "D" - mostly quantitative with some qualitative components, zone "E" - exclusively quantitative methods.

Rice. Qualitative-mixed-quantitative continuum

If we talk about specific designs of ICT, then there are two main typologies. One is suitable for the case when qualitative and quantitative methods are used on different stages one study, the other - for the case when the research project uses alternating or parallel qualitative and quantitative research.
The first typology includes six mixed designs (see Table 4.2). An example of research that uses qualitative and quantitative methods at different stages is concept alignment. Within this research strategy, data collection is carried out using qualitative methods (for example, brainstorming or focus groups), and analysis is quantitative (cluster analysis and multivariate scaling). Depending on the tasks being solved (search or descriptive), it can be attributed either to the second or to the 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 mixed-type research, 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 one is 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 the first and which is the second in the time dimension. An example of a research project that fits this typology is when the first phase is qualitative research in order to build a theory (for example, using the “grounded theory” of Anselm Strauss), and on the second - a quantitative survey of a specific group of people 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 study designs using qualitative and quantitative methods within the same study*

* In this table, designs 2-7 are mixed, design 1 is completely qualitative, design 8 is completely quantitative.

Table 2. Mixed Research Designs Using Qualitative and Quantitative Research as Different Phases of the Same Research Project*

* "quality" means qualitative research, "quant" - quantitative; "+" - simultaneous research, "=>" - sequential; capital letters indicate the main status of the paradigm, small - subordinate.

Of course, these typologies are not limited to the full range of research designs and should be considered as possible guidelines for ICT planning.
ICT Designs in Evaluation Studies.
According to the typology of ICT 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 framework of one study, they are used separately from each other. In integrative design, methods belonging to different paradigms, on the other hand, are used together.
The component type includes three types of designs: triangular, complementary, and expansive. In triangulation design, results from one method are used to validate results 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 that are of secondary importance. When using expansive design, apply various methods to obtain information on various aspects of evaluation, i.e. each method is responsible for a specific piece of information.
The integrative type includes four types of designs: iterative, unstitched, holistic, and transformational. In iterative design, the results of one method prompt or direct other methods that are relevant to the situation. Nested design is associated with situations where one of the methods is integrated into another. Holistic design involves the combined use of integrated qualitative and quantitative methods in order to comprehensively evaluate a program. In this case, both groups of methods have an equivalent status. Transformational design takes place when different methods are applied together to fix value views, which are subsequently used to reconfigure a dialogue whose participants adhere to different ideological positions.