1. YOUR STEPS ON RESEARCH STAIRS Center of Excellence in Cancer Research Tanta University February 16. 2015 Dr. Mohamed Labib Salem, PhD Prof. of Immunology Director, CECR

2. Search Versus Research

3. “is to see what everybody else has seen, and to think what nobody else has thought" Albert Szent-Gyorgyi, 1937 Nobel Prize; Medicine Laureate Research?

4. RESEARCH

5. Phases of Research Skills Student Technician Researcher Scientists Outstanding scientist

6. Research Skills Intellectual skills Technical skills Expertise (experience)

8. صفات الباحث الامانة العلميه الجدية المعاملة الحسنه التعاون الطموح قارء ومحلل التواضع -----

9. Research Misconduct Falsification Fabrication Plagiarism

11. Systematic solving of scientific problems Using scientific methods System of interconnecting phases and steps Characteristic features of research

12. Steps in the Research Process ● Step I: Define the research problem ● Step 2: Developing a research plan ● Step 3: Collecting data ● Step 4: Analysing research data ● Step 5: Presenting the findings 8- 3

13. 1. Phase of concepcion 2. Phase of elaboration of research plan 3. Empiric phase 4. Analytic phase 5. Disseminative phase Phases of research process

14. The research process should be understood as one of ongoing planning, searching, discovery, reflection, synthesis, revision, and learning.

15. Researchers work in graphic form Searching for scientific problem Review of literature H y p o t h e s i s Aims of research M e t h o d s Plan of research Research Results

16. - The phase in which content and structure of research are created  Conceptualisation refers to the process of developing refining abstract ideas. The activities include thinking, rethinking, theorising, making decision, and reviewing ideas. It is composed of 4 steps: 1) Formulation and set bounds of research problem, determine the purpose of study 2) Searching and review the literature related to the research problem 3) Development of theoretical construction of the future research 4) Creation of hypothesis I. Phase of Conception

17. II. Phase of elaboration of proposal and research plan It is a general plan of research : – selection of patients, animals, other objects used for solving the problem: - creation of representative sample, inclusion, exclusion criteria – selection of the methods –qualitative, quantitative – creation of pilot study – selection of methods – selection of research technology – development a protocol of research – to define the schedule of research

18. III. Empiric phase The aim of this phase is production of results, collection of data, and their preparation for next analysis The results are produced by: – experiment on animals – by clinical study – by using questionaire, interview, observation – by using models - biological, electronic, mathematic....

19. IV. Analytic phase The content of this phase is: – kvantitative analysis of the data – kvalitative analysis of the data – statistic analysis of the data – interpretation of the results Methods used in analytic phase: corelation - corelation: looking for relationships among the two or more values comparation - comparation: comparation of the result obtained in our research with similar research done by other researchers

20. V. Disseminative phase It is the phase when results of the research are published as: research report lectures and posters at the congresses and conferences papers in journals......

21. From an idea to a hypothesis

22. : Problem

23. “All the forces in the world are not so powerful as an idea whose time has come” Victor Hugo Think globally and apply locally Idea? A novel thinking for solving a problem

24. Does it test a hypothesis or a concept? Does it fit the focus of my organization, my department, institution, and profession? Has it or a similar study been done before? Is it important and make a difference? Does it fill a gap in knowledge or lead to a greater understanding? Has it or a similar study been done before? Does it worth to spend considerable time thinking, reading and doing? Coming up with a bright IDEA!

25. Is it translational? Is it based on your preliminary data? Is it based on your own observations? Is it based on your reading? Is it based on others’ expertise? Is it descriptive? Is it mechanistic? Question your Idea

26. State it after you present the problem Provide the solution for a specific problem. It indirectly expresses the goals (SPECIFIC AIMS). It should be testable. Funnel the reader to the hypothesis – at the end of the background/significance section Prof. Mohamed Labib Salem, PhDCompetitive Project Unit (CPU), Tanta University Hypothesis

27. Formalized hypotheses contain two variables One is "independent" and the other is "dependent." The independent variable is the one you, the "scientist" control the dependent variable is the one that you observe and/or measure the results. Hypothesis

29. The 5 W + H: Proposal Railway 1.What (Problem) 2.Why (Significance) 3.Who (PI and Co-PIs) why 4.Where (Facility) why 5.When (Time Line) +How (Methods) why 29

32. The Application of the Scientific Method: Preclinical Trials Copyright 2010. PEER.tamu.edu

33. Phase II study Phase III study In vitro models Preclinical Studies Phase I study Industry (Market) Industry (Market) BENCH Phases of Research From Bench to Clinic Clinical studies

35. Are the processes by which scientists test drugs and devices to see if they are SAFE and EFFECTIVE. Pre-Clinical Trials and Clinical Trials

36. What is a Preclinical Trial? Preclinical trial - a laboratory test of a new drug or a new medical device, usually done on animal subjects, to see if the hoped-for treatment really works and if it is safe to test on humans.

37. There are two types of Research: Basic and Applied Basic Research: discovering new facts about how things work, how they are made, or what causes a biological event to occur. Basic research can explore a topic, explain a topic or describe a topic. For Example: A researcher discovered that genes can be turned off or on by small RNA molecules in the body. This study was conducted on worms. It led to the Nobel Prize in 2006.

38. “Basic” vs. “Applied” Research Applied Research: Taking the information discovered in basic research and investigating how to use it to treat and prevent sicknesses. Example: A researcher uses the information about turning genes off and on to find a drug that is used to turn off genes that cause diseases and disorders in humans. Segment of DNA. Many such segments act as genes.

39. Where Do We Get New Ideas For Research? Ideas come from all kinds of scientists and medical professionals who do research in universities, government labs, and in corporations.

40. Take a Minute to Discuss: What is a Pre-Clinical Trial? What is the difference between basic research and applied research? What sickness or disease would you like to see an effective treatment for?

41. There are several steps involved with doing a Pre-Clinical Trial: File for approval as an Investigational New Drug (IND) 5 4 3 2 1 Establish Effective and Toxic Doses Screen the Drug in the Assay Develop a Bioassay Indentify a Drug Target

42. Steps in Doing a Pre-Clinical Trial: Drugs usually act on either cellular or genetic chemicals in the body, known as targets, which are believed to be associated with disease. Scientists use a variety of techniques to identify and isolate individual targets to learn more about their functions and how they influence disease. Compounds are then identified that have various interactions with the drug targets that might be helpful in treatment of a specific disease. Step One: Get an idea for a drug target.

43. Finding the Right Target Is Not Easy Parkinson’s Disease Example: Parkinson's disease: a disease which causes deterioration of the central nervous system over a period of time. This disease often impairs the patient’s movement, speech, and other functions.

44. Tremors or shaking occurs when cells in one part of brain die. These cells communicate using a chemical called dopamine. Drugs that replace dopamine work only for a few years. Other Parkinson’s symptoms (depression, sleep disorder, digestive problems, loss of brain function) have other causes. Another sign of Parkinson’s disease: many cells have deposits of a protein, synuclein. Four drug companies are developing drugs to counter synuclein, even though nobody knows if it is a cause or a consequence of Parkinson’s. Synuclein could be like a tombstone—a marker, not a cause of cell death. How is Parkinson’s treated? Where should the focus be?

45. targetbiochemical pathways Drugs target specific points in biochemical pathways Biochemical pathways Biochemical pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by chemical reactions. Examples of different types of biochemical pathways: A E B D C A B C D E Any step in the pathway, for example from A to B, or B to C, might be a target for the right drug. * See slide note

46. Bioassay Step Two: Develop a Bioassay A Bioassay is a “live” system that can be used to measure drug effect. It may be a culture of cells or organs or a whole animal. For example: Zebra-fish embryos - you can see effects of drugs on bone density, blood vessel growth and many other systems of the zebra-fish. Steps in Doing a Pre-Clinical Trial:

47. This is the actual test of the drug on the chosen bioassay. This will determine if the drug is SAFE and if it is EFFECTIVE in the bioassay (BEFORE it is ever tested on humans!) Steps in Doing a Pre-Clinical Trial: Step Three: Screen the drug in the Bioassay.

48. Most drugs have a toxic level or an amount at which the drug will become harmful instead of helpful. Steps in Doing a Pre-Clinical Trial: Step Four: Establish what dosage amount of the drug is safe and what dosage amount of the drug is toxic.

49. IND must show how the drug: Is manufactured. Appears (color, solubility, melting point, particle size, moisture content). Formulated (pills, liquid, etc. + inactive ingredients). Will be analyzed for purity, concentration, stability. Will be tested for safety (this will be the basis for allowing first use in humans). Steps in Doing a Pre-Clinical Trial: Step Five: Application is made to the Food and Drug Administration (FDA) as an Investigational New Drug (IND).

50. Think Break: How are these steps like the steps of the Scientific Method? Why would research scientists use a Bioassay instead of a human subject to test a new drug? What percentage of drugs do you think get this far in the process?

51. Review: Steps to New Drug Discovery Pre-Clinical Trials target Get idea for drug target bioassay Develop a bioassay Screen Screen chemical compounds in assay Establish effective and toxic amounts an Investigational New Drug (IND) File for approval as an Investigational New Drug (IND) (leads to clinical trials)

52. Can you summarize the process? With a partner or your group, write a summary of the Pre-Clinical Trial Process. Use the following words to help you: Drug Safe Effective Basic Research Applied Research Target Biochemical Pathway Bioassay Toxic Investigational New Drug (IND)

53. ETHICAL REGULATIONS AND STANDARADS We have to be cared for properly. It’s the law!!!!!!!

54. Institutional Animal Care and Use Committees (IACUCs) Required at all research institutions. Committees consist of veterinarians, scientists, members of the public. Without IACUC approval, no research using animals may proceed. Among IACUC considerations are the measures used to control potential pain and avoid distress as well as the potential value of any scientific outcome from the proposed studies.

55. The Three Rs Three R’s The Three R’s are principles of good science that scientists must adhere to when conducting animal-based research.

56. The Three “Rs” 1.Refine- 1.Refine- consider alternatives to any procedure that causes more than momentary pain or distress. 2.Reduce- 2.Reduce- the number of animals used should be the minimum that is consistent with the aims of the experiment. 3.Replace- 3.Replace- use non-animal models when possible (e.g., in vitro methods).

57. The Three R’s of using animals in research The First R- Replacement Using non-animal alternative wherever they exist in order that the only research done using animals is that which can be done no other way. This is a synthetic skin. It can be used in some research situations.

58. The Second R: Reduction The Second R: Reduction: Using as few animals as possible to attain statistically significant results, as well as finding ways to cut down on the number of animals used for any specific piece of research. The Three R’s of using animals in research

59. This is a laboratory animal care technician. Read about him at: http://www.kids4research.org/teachers_parents/aces_Gary.asp Watch a short video of a technician at: http://www.aboutbioscience.org/laboratory_animal_technician.html http://www.kids4research.org/teachers_parents/aces_Gary.asp http://www.aboutbioscience.org/laboratory_animal_technician.html The Third R: Refinement Improving animal welfare in laboratories by enhanced lab technician training, better enrichment inside the cages for animals, redesign of an experiment, etc. The Three R’s of using animals in research

60. Abstract Introduction Background Oobjectives Experimental Design Methods Facilities and Equipments Budget References Appendices (any additional documents) Project Anatomy

63. خطوات استراتيجية حل المشكلات

65. الملخص: خطة العمل تحديد مجال البحث القراءة حول نقطة البحث ايجاد مشرف من المتخصصين تحديد المشكلة واسبابها طرح فكرة هل المشكلة البحث عن المساعدين كتابه المشروع تقديمه للجهة المنحة

67. « نحن أطفال نلعب علي شاطئ العلم « أينشتاين

68. Mohamed L. Salem Good luck E-mail: mohamedlabibsalem@yahoo.com Tel. 01274272624