(I) MEDICAL RESEARCH_ UNIT_III_RESEARCH METHODOLOGY & BIOSTATISTICS.pptx

Research Methodology and Biostatistics syllabus:
Medical Research: History, values in medical ethics, autonomy, beneficence, non-maleficence, double effect, conflicts between autonomy.
Medical research has a long and varied history. It has evolved from rudimentary practices to sophisticated, evidence-based methodologies. Some key milestones include the development of the scientific method, the use of randomized controlled trials, the discovery of antibiotics, and the mapping of the human genome. Ethical concerns have also played a significant role in shaping the history of medical research, especially in response to various ethical violations, such as the Tuskegee Syphilis Study and the Nuremberg Trials.
Resolving conflicts between these principles often requires careful consideration, ethical analysis, and, in some cases, consultation with ethics committees or boards. The specific course of action may vary based on the individual circumstances and ethical frameworks employed by healthcare professionals and researchers. Ethical guidelines and regulations also play a significant role in addressing and preventing these conflicts in medical research.

1. MEDICAL RESEARCH : “RESEARCH METHODOLOGY & BIOSTATISTICS” PRESENTED & WRITTEN by: *Prachi Pandey, RAHUL PAL M. PHARM (PHARMACEUTICS), IiI rd Sem. DEPARTMENT OF PHARMACEUTICS, NIMS INSTITUTE OF PHARMACY, NIMS UNIVERSITY, JAIPUR, RAJASTHAN, 303121, India.

2. INTRODUCTION Medical research in clinical settings is the study of human health and disease in people. It is the primary way that researchers determine if a new form of treatment or prevention, such as a new drug, diet, or medical device, is safe and effective in people. A clinical trial is designed to learn if a new treatment is more effective or has less harmful side effects than existing treatments . Clinical trail is basically have 4 phases. Phase I, Phase II, Phase III, Phase IV

3. PHASES OF CLINICAL TRAILS

4. HISTORY T he most important figures in the history of medical research is Louis Pasteur. Pasteur was is known as medical microbiologist. A French chemist and microbiologist who made significant contributions to the understanding of infectious diseases. In the 1860s, Pasteur showed that germs caused disease and that they could be killed by heat. This discovery led to the development of pasteurization, a process of heating food to kill harmful bacteria .

5. HISTORY T he history of medical research is Robert Koch. Koch is also known as Father of modern microbiologist. He was a German physician and microbiologist who is credited with discovering the bacteria that cause tuberculosis and cholera. Koch's work led to the development of new treatments and preventive measures for these diseases . He was awarded the Nobel Prize in Medicine in 1905 . He is one of the founders of microbiologist Robert Koch (1843 - 1910)

6. HISTORY In the 20th century, medical research accelerated rapidly. This was due to a number of factors, including the development of new technologies, such as the electron microscope and the DNA sequencing machine. These technologies allowed scientists to learn more about the human body and disease than ever before.

7. Value in medical ETHICS Medical ethics in medical research is a complex and evolving field. It is concerned with the ethical implications of research involving human subjects. The goal of medical ethics is to ensure that the rights and well-being of research participants are protected, while still allowing for valuable research to be conducted. There are a number of ethical principles that guide medical research involving human subjects. These principles include: Autonomy Beneficence Non-maleficence

8. Autonomy Autonomy in medical research is the principle that research participants should have the right to make their own decisions about whether or not to participate in research, and they should be provided with all of the relevant information about the research before they make a decision. This principle is important because it respects the right of individuals to make their own choices about their bodies and their health. It also helps to ensure that research participants are fully informed about the risks and benefits of the research, and that they are not coerced into participating. Inform Concent form

9. How to apply Autonomy Informed consent:  Research participants must be given all of the relevant information about the research before they consent to participate. This information should include the purpose of the research, the methods that will be used, the risks and benefits, and the alternatives to participation. For example, in a clinical trial for a new drug, participants must be informed of the potential side effects of the drug, as well as the risks of taking a placebo. Right to refuse : Research participants have the right to refuse to participate in research at any time, without giving a reason. Researchers should not try to pressure or coerce participants into participating in research. Respect for participant preferences:  Researchers should respect the preferences of research participants. For example, participants may have preferences about the type of research they are willing to participate in, or the procedures that they are willing to undergo. Researchers should also respect the participants' right to withdraw from research at any time.

10. Examples of autonomy in medical research A patient is diagnosed with a terminal illness. The patient is offered the opportunity to participate in a clinical trial of a new drug that is being developed to treat the illness. The patient is given all of the information they need about the clinical trial, including the potential risks and benefits. The patient decides to participate in the clinical trial, but later changes their mind and wants to withdraw. The researchers must respect the patient's decision and allow them to withdraw from the clinical trial at any time . A pregnant woman is offered the opportunity to participate in a clinical trial of a new drug to prevent a rare genetic disease. The drug has not been tested in pregnant women before, and there is a risk that it could harm the fetus. The woman is given all of the information she needs about the clinical trial, including the potential risks and benefits. The woman decides to participate in the clinical trial, but she also wants to have the option to terminate her pregnancy if she decides that the risks are too high.

11. Beneficence Beneficence in medical research is the ethical principle of promoting the welfare of research participants and maximizing the potential benefits of research while minimizing any potential harm. It is one of the four core ethical principles of research ethics, along with respect for persons, justice, and nonmaleficence . The principle of beneficence is based on the belief that we have a moral obligation to help others and to do what is best for them. In the context of medical research, this means that researchers have a responsibility to design and conduct research studies in a way that minimizes the risks to participants and maximizes the potential benefits. Data safety monitoring boards ( DSMBs)

12. How to apply Beneficence Careful design of research studies:  Researchers should carefully design their studies to minimize the risks to participants and maximize the potential benefits. This includes carefully considering the study population, the interventions being studied, and the methods being used. Informed consent:   Research participants must be fully informed of the risks and benefits of participating in a study before they can give their consent. Researchers have a responsibility to provide participants with all of the information they need to make an informed decision about whether or not to participate. Continuous monitoring of participants:   Researchers should continuously monitor participants during the study to identify any potential harms. If any harms are identified, researchers should take steps to mitigate them. Data safety monitoring boards (DSMBs ):  DSMBs are independent groups of experts who review data from clinical trials to assess the safety and efficacy of the interventions being studied. DSMBs can recommend that a trial be stopped early if the risks to participants outweigh the potential benefits.

13. Examples of beneficence in medical research Developing new vaccines and treatments for diseases:   This is one of the most important and direct ways in which beneficence is promoted in medical research. By developing new vaccines and treatments, researchers can help to prevent and cure diseases, thereby improving the health and well-being of individuals and society as a whole. Conducting clinical trials to ensure the safety and efficacy of new medical interventions:  Before a new medical intervention can be widely used, it must be thoroughly tested to ensure that it is safe and effective. Clinical trials are essential for this purpose. By participating in clinical trials, research participants help to ensure that new medical interventions are safe and effective for everyone.

14. Examples of beneficence in medical research Studying the long-term effects of medical treatments. Many medical treatments have long-term effects, both positive and negative. Researchers have a responsibility to study these long-term effects so that they can better understand the risks and benefits of different treatments and make recommendations to patients and healthcare providers. Conducting research to improve the quality of life for patients with chronic diseases. Chronic diseases, such as cancer, heart disease, and diabetes, have a significant impact on the quality of life of patients and their families. Researchers are constantly working to develop new ways to improve the management of chronic diseases and improve the quality of life for patients. Developing new methods for diagnosing and treating diseases. New diagnostic and treatment methods can help to improve the accuracy and timeliness of diagnosis, as well as the effectiveness of treatment. Researchers are constantly working to develop new and improved methods for diagnosing and treating a wide range of diseases .

15. Non- Maleficence Non-maleficence in medical research is the ethical principle of avoiding or minimizing harm to research participants. It is one of the four core ethical principles of research ethics, along with beneficence, autonomy, and justice. Non-maleficence is important in medical research because it ensures that research participants are not subjected to unnecessary risks. It also helps to ensure that research is conducted in a safe and responsible manner. Continuous Monitoring

16. How to apply Non- Maleficence Careful design of research studies:  Researchers should carefully design their studies to minimize the risks to participants. This includes carefully considering the study population, the interventions being studied, and the methods being used. Informed consent:   Research participants must be fully informed of the risks and benefits of participating in a study before they can give their consent. Researchers have a responsibility to provide participants with all of the information they need to make an informed decision about whether or not to participate. Continuous monitoring of participants:   Researchers should continuously monitor participants during the study to identify any potential harms. If any harms are identified, researchers should take steps to mitigate them. Data safety monitoring boards (DSMBs ):  DSMBs are independent groups of experts who review data from clinical trials to assess the safety and efficacy of the interventions being studied. DSMBs can recommend that a trial be stopped early if the risks to participants outweigh the potential benefits .

17. How to apply Non- Maleficence Use validated research methods and instruments :   This will help to ensure that the research is conducted in a safe and reliable manner. Pilot test new methods and procedures before using them with participants :  This will help to identify any potential risks and make necessary adjustments. Use the least invasive methods possible :  This means using methods that are less likely to cause discomfort or harm to participants. Provide participants with appropriate support and resources :  This may include providing participants with access to medical care, financial assistance, or counseling. Respect the confidentiality and privacy of participants:  This means taking steps to protect participants' personal information and ensuring that they are not identified in any published reports or presentations .

18. Examples of NON- MALEFICENCE in medical research A researcher is developing a new drug for treating cancer. The researcher knows that cancer is a serious and deadly disease, and that there is a need for new and effective treatments. However, the researcher also knows that developing new drugs is a complex and challenging process, and that there is always the risk of side effects, even serious ones. The researcher carefully considers the potential risks and benefits of the new drug before starting a clinical trial. The researcher also takes steps to minimize the risks to participants. For example, the researcher starts by testing the drug in a small group of healthy adults to assess its safety. Once the drug is shown to be safe in this group, the researcher expands the trial to include more participants, including people with cancer. The researcher also continuously monitors participants for any potential harms. If any harms are identified, the researcher takes steps to mitigate them. For example, if a participant experiences a serious side effect, the researcher will remove the participant from the trial and provide them with appropriate medical care .

19. Double effect The doctrine of double effect (DDE) is a moral principle that can be applied to medical research to justify actions that have both intended and unintended effects, where the intended effects are good and the unintended effects are unavoidable. The DDE is often used in medical research to justify the use of animal models and the conduct of clinical trials, which both have the potential to harm participants but also have the potential to benefit society as a whole. The DDE has four main criteria: The intended effect must be good. The unintended effect must be foreseen but not intended. The unintended effect must not be a means to achieving the intended effect. The good effect must outweigh the bad effect.

20. Examples of DOUBLE EFFECTS in medical research Researchers develop a new drug to treat cancer, but the drug has the potential to cause serious side effects, including death. The researchers conduct a clinical trial of the drug, and some of the participants experience serious side effects, but the drug is also effective in treating cancer. The ethical justification for conducting the clinical trial is that the good effect (developing a new and effective cancer treatment) outweighs the bad effect (the potential to harm participants). Researchers study a new experimental treatment for Alzheimer's disease in mice. The treatment is effective in reducing the symptoms of Alzheimer's disease in mice, but it also causes some of the mice to experience pain and distress. The ethical justification for using mice in this research is that the good effect (developing a new and effective treatment for Alzheimer's disease) outweighs the bad effect (the harm caused to the mice).

21. Medical Ethics Definition Examples Autonomy The right of patients to make their own decisions about their healthcare, even if those decisions are not in their best interests. A patient has the right to refuse a life-saving blood transfusion, even if it means that they will die. Beneficence The duty of healthcare professionals to act in the best interests of their patients. A doctor prescribes a medication to a patient to relieve their pain, even though the medication has some side effects. Non-maleficence The duty of healthcare professionals to avoid harming their patients. A surgeon refuses to perform a risky surgery on a patient, even though the surgery could potentially save their life. Double effect A principle that allows healthcare professionals to perform an action that has both good and bad effects, as long as the good effect is the primary intention and the bad effect is an unavoidable side effect. A doctor gives a patient a chemotherapy drug that kills cancer cells, but also damages healthy cells. Conflicts between autonomy and beneficence/non-maleficence Situations where a patient's autonomous decision is not in their best interests, or where acting in the patient's best interests would violate their autonomy. A Jehovah's Witness patient refuses a blood transfusion, even though they need it to survive. A doctor wants to force-feed a patient who is refusing to eat, even though the patient is competent and understands the consequences of their decision.

22. REFERENCES Guraya , S. Y., London, N. J. M., & Guraya , S. S. (2014). Ethics in medical research.  Journal of Microscopy and Ultrastructure ,  2 (3), 121-126 . Hoeyer , K., & Hogle , L. F. (2014). Informed consent: The politics of intent and practice in medical research ethics.  Annual Review of Anthropology ,  43 , 347-362.