Clinical studies. BARBORA VLKOVÁ INSTITUTE OF MOLECULAR BIOMEDICINE

Transcription

1 Clinical studies BARBORA VLKOVÁ INSTITUTE OF MOLECULAR BIOMEDICINE

2 Biomedical research 1. Basic research a. In vitro = cell cultures b. In vivo = experimental animals c. In silico = performed on computers 2. Clinical research clinical studies a. Observational studies b. Clinical trials (intervention studies) c. Translational research (from bench to bedside)

3 Basic research knowledge and insights no immediate application direct short-term benefit cannot be predicted provides the scientific basis for further research no scientific and medical breakthroughs without basic research similarity & differences between humans and animals

4 Xenotransplantation Cell cultures Artificial systems Limited insight Physiological processes and diseases can only be studied on the living organism

5 Basic research & medical progress An example of the development of treatment methods for diabetes mellitus Experiments on rabbits, dogs, pigs and cows Nobel Prize 1923

6 Basic research & medical progress

7 Basic research & medical progress Serum therapy tested on animals, is the basis for vaccinations. Emil von Behring the Nobel Prize in Medicine in 1901.

8 Animals in science physiological mechanism patophysiological mechanism anatomy effect of drugs toxicological evaluations and safety tests surgical procedures function of individual genes development of medical products and devices tests and checks of medical products and devices

9

10

11 The best test species for humans is humans 3R strategy for animals Replacement = non-animal methods to achieve the same scientific aim Reduction = a smaller number of animals Refinement = improvement the experiments so that animals do not suffer

12

13 CIA

14

15

16 Computer tomography (CT)

17 Transplantation medicine the surgical techniques procedures to avoid rejection new findings on immunosuppression to identify species whose organs are suitable for transplantation xenotransplantation is controversial ethical considerations & immune rejections genetically modified animals

18 Genome research investigates the genetic make-up of living organisms effects on the phenotype of an animal genetically modified animals (transgenic animals) spontaneous changes to the genome (mutations) genetic modification of flies, round worms, zebrafish, mice, rats, pigs

19 Genome research the mouse and human genome exhibit major similarities both are fully decoded a variety of genetically modified mouse strains exist that can be used as model systems for studying human diseases observing any differences from normal behaviour or physiology, researchers can infer its probable function

20 Neuroscience Nobel prize in 2000, signal transduction in the nervous system (mice, rats, rabbits, guinea pigs and marine gastropods) Nobel prize in 2013, the transport processes within a nerve cell (rats, hamsters and genetically modified) Nobel prize in 2014, spatial orientation in mammals (rats)

21 Neuroscience stroke Alzheimer s and Parkinson s disease multiple sclerosis epilepsy depression schizophrenia anxiety disorders

22

23 Increased intelligence through genetic engineering

24 Biomedical research 1. Basic research a. In vitro = cell cultures b. In vivo = experimental animals c. In silico = performed on computers 2. Clinical research clinical studies a. Observational studies b. Clinical trials (intervention studies) c. Translational research (from bench to bedside)

25 Observational studies Passive study Descriptive study (1 group) Comparative study (2 groups) Case-control study (matching) Cross-sectional study (one time point) Longitudinal study Retrospective known results, unknown factors Case-control study (matching) Prospective known factors, unknown results Case-control study (matching)

26

27 Retrospective study

28

29 Prospective study

30 Interventional studies = clinical trails - drugs, vaccines, diagnostic methods, instruments Large cohort Control group Statistical analysis Randomisation Blind/double/triple blind design Placebo Nocebo

31

32 Phases of clinical trails 0th Pre-clinical phase (5y) 1st Clinical phase (n=30) 2nd Clinical phase (n=200) 3rd Clinical phase (n=2000) Registration (1y) 4th Clinical phase (n=20 000) 14y

33

34

35

36 Subjects

37 Pharmacodynamic Analyses

38 Safety and Tolerability Conclusions: A single dose of solanezumab was generally well tolerated. A dose-dependent change in plasma and CSF AA was observed, although changes in cognitive scores were not noted.

39

40

41

42

43

44

45

46

47

48

49

50 originally as AIDS Clinical Trials Information System a registry of clinical trials United States National Library of Medicine at the National Institutes of Health 230,000 trials from 195 countries

51

52

53

54

55

56 Diagnostic studies diagnostic method diagnosis - population Sensitivity Specificity Positive predictive value Negative predictive value Diagnostic accuracy

57 Sensitivity Ability of the test to find the individuals with disease % 10/10 = 100% - could contains also false positive results 20/21 = 95% 50/60 = 83% 22/40 = 55%

58 Specificity Ability of the test to find the healthy individual %

59

60 Positive predictive value PPV Probability that positive result really means presence of the disease % = positive results of the test all positive results of the test (including false positive results)

61 Negative predictive value Probability that negative result really means absence of the disease % = negative results of the test all negative results of the test (including false negative results)

62 Diagnostic accuracy Probability of correct result % = positive + negative results of the test all positive + negative results of the test (including false positive + false negative results)

63 Diagnostic accuracy

64

65 Preparation of the study hypothesis choice of design of the study sample size patients protocol financing etical questions methods

66 Translational research T1 T2 analysis of samples with new methods no drug testing no standard diagnostics methods application of outcomes into the practice extrapolation of the results to new groups modification of protocols already approved drugs cross-functional collaborations (researchers & clinicians)

67 bench to bedside and back research

68

69 ... the use of animals in scientific testing has always been and will continue to be a controversial subject...