1. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Introduction Clinical trials

2. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Introduction Controlled clinical trials are the best way to test whether a treatment is better than other treatments (or no treatment). Interventions for preventing or treating health problems are examined in a safe and efficient way.

3. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Introduction As a patient, you might be considering enrolling in a clinical trial or you might be invited to by your physician. If you are interested in the evaluation of existing and new treatments, you can also be proactive and increase your knowledge about clinical trials by yourself.

4. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Introduction This tutorial will familiarize you with the most important facts about clinical trials. We hope it will answer many of the questions you may have about them.

5. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Introduction Let‘s agree on words! The process we are going to describe is typical of new drug development, but also applies to any other type of intervention, such as diagnostic strategies, surgical procedures, lifestyle changes (diet, exercise, etc.) or comparisons between new and existing therapies in terms of effectiveness and safety. To make things easier, we will use the word “treatment” to refer to any type of intervention. Let‘s agree on words! The process we are going to describe is typical of new drug development, but also applies to any other type of intervention, such as diagnostic strategies, surgical procedures, lifestyle changes (diet, exercise, etc.) or comparisons between new and existing therapies in terms of effectiveness and safety. To make things easier, we will use the word “treatment” to refer to any type of intervention.

6. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary What are controlled clinical trials?

7. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary What are clinical trials? Controlled clinical trials aim to improve existing treatments or to replace them with new and better ones. Before a new treatment is made available for patients, it must be tested in controlled clinical trials for efficacy and safety.

8. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary What are clinical trials? Controlled clinical trials are designed to help us learn more about the positive and negative effects of treatments. A treatment‘s efficacy and safety can only be fully assessed after long-term use on patients in everyday clinical practice.

9. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary What are clinical trials? Before new drug treatments are tested in patients in clinical trials they must be carefully evaluated in laboratories. If the results of laboratory studies of a possible treatment are promising, clinical trials are designed to assess its possible beneficial and adverse effects in patients

10. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary What are clinical trials? New treatments need to be evaluated statistically in clinical trials involving large numbers of similar patients. Results must be reviewed systematically and carefully analysed.

11. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary What are clinical trials? Controlled clinical trials conducted on large numbers of patients are essential for assessing the efficacy and safety of new treatments. TrueFalse

12. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary What are clinical trials? Controlled clinical trials conducted on large numbers of patients are essential for assessing the efficacy and safety of new treatments. TrueFalse Your choice is correct!

13. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary What are clinical trials? Controlled clinical trials conducted on large numbers of patients are essential for assessing the efficacy and safety of new treatments. TrueFalse Your choice is not correct!

14. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary What are clinical trials? New treatments that have been tested in a laboratory have no risks whatsoever when used in clinical trials. TrueFalse

15. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary What are clinical trials? New treatments that have been tested in a laboratory have no risks whatsoever when used in clinical trials. TrueFalse Correct! Laboratory tests help designing new treatments but cannot reveal risks for patients.

16. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary What are clinical trials? New treatments that have been tested in a laboratory have no risks whatsoever when used in clinical trials. TrueFalse Wrong! New treatments can always have unknown and unpredictable risks.

17. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Why are controlled clinical trials important?

18. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Why are clinical trials important? Controlled clinical trials help to develop new and better treatments for patients. Assessing efficacy and safety of a new treatment is a very rigorous and often long process. For this reason, new treatments usually take a lot of time before becoming publicly available.

19. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Why are clinical trials important? Clinical trials aim to enhance new or existing treatments and diagnostic strategies.

20. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Why are clinical trials important? Clinical trials are important because they investigate and compare new and existing treatments, thus promoting progress in treatment.

21. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Are you considering enrolling in a clinical trial?

22. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Enrolling in Clinical Trials? Patients enroll in clinical trials for several reasons. Many people hope to benefit from having access to a new treatment.

23. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Enrolling in a clinical trial? To avoid disappointment you should remember that new treatments are almost as likely to be worse as to be better than standard treatments. Indeed, that‘s why controlled clinical trials are needed!

24. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Enrolling in a clinical trial? Patients should consider participating in a clinical trial if there is a good chance that they will benefit from the new treatment. Controlled clinical trials provide an opportunity for them to receive new, experimental treatments that are not yet generally available. This is especially true for diseases with no known cure.

25. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Enrolling in a clinical trial? Clinical trial participants also often wish to contribute to research to help other patients by participating in clinical trials.

26. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Enrolling in a clinical trial? The results of clinical trials always represent an improvement of the standard available treatment. TrueFalse

27. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Enrolling in a clinical trial? The results of clinical trials always represent an improvement of the standard available treatment. TrueFalse No! Even if many clinical trials result in an improvement there is no guarantee of this. A new treatment could be as good as or even worse the standard treatment.

28. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Enrolling in a clinical trial? The results of clinical trials always represent an improvement of the standard available treatment. TrueFalse Yes! But new interventions are only very slightly more likely than not to prove better than standard treatments.

29. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Enrolling in a clinical trial? Researchers conducting an ethical clinical trial hope that their new treatment will prove to be superior to standard treatments already available. TrueFalse

30. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Enrolling in a clinical trial? Researchers conducting a clinical trial hope that their new treatment is better than the standard one already available. TrueFalse Your choice is not correct! Reseachers always conduct a clinical trial in the hope of improving treatment

31. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Enrolling in a clinical trial? Researchers conducting a clinical trial hope that their new treatment is better than the standard one already available. TrueFalse Correct! Although disappointment is possible, researchers always hope to achieve an improvement

32. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process

33. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process Every clinical trial is designed to answer questions about the effects of treatments being compared. The quality of a clinical trial and its results depend heavily on a well chosen question, building on existing evidence, and on good clinical trial design.

34. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process When conducting a clinical trial, researchers must follow a written study plan, also called a study protocol. The protocol helps to ensure patients‘ safety and is essential for achieving high quality and reliable results.

35. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process Some clinical trials are conducted on one group of patients only, whilst most compare two groups. Patients in different comparison groups must be as similar as possible e.g. they must have the same medical conditions, at the same stage of a disease.

36. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process Patients are assigned to one group or another (for example, to receive a new treatment or a standard one) by a method called randomisation, or random allocation/assignment. Chance (using a random number generator or some equivalent) is used to decide the allocation sequence/plan. This type of clinical trial is called a randomized trial.

37. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process Sometimes, one group in a 2-group randomized trial is referred to as ‘the experimental group’ or ‘the active group’, and the comparison group is called ‘the control group’.

38. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process The control group in a clinical trial is treated with the same care as the active group. If possible, neither the researchers nor the patients should know to which group every participant has been assigned. This special type of clinical trial is called a blinded or masked trial and it helps to ensure comparability between the comparison groups when treatment outcomes are assessed.

39. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process For some diseases there are no standard treatments available. And in this situation the control group receives a dummy treatment called a placebo, such as a sugar pill. Important For ethical reasons, placebo control groups are not allowed if an effective treatment already exists and patients can benefit from it. In these circumstances, patient allocated to the control group should receive the best standard treatment.available.

40. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process When testing a new treatment, controlled clinical trials must give priority to protecting patients‘ safety and wellbeing. TrueFalse

41. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process When testing a new treatment, controlled clinical trials must give priority to protecting patients‘ safety and wellbeing. TrueFalse Correct!

42. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process When testing a new treatment, controlled clinical trials must give priority to protecting patients‘ safety and wellbeing. TrueFalse Incorrect! Clinical trials are first and foremost committed to patients‘ safety and only secondarily to scientific results.

43. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process The control group always receives the less effective treatment. TrueFalse

44. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process The control group always receives the less effective treatment. TrueFalse Incorrect! Before the clinical trial is completed, it is not possible to know which treatment will be better - standard or new. Both treatments could be equally helpful for patients.

45. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process The control group always receives the less effective treatment. TrueFalse Correct! When starting a clinical trial, there is uncertainty about whether the standard therapy or the new treatment will turn out to be better. And both treatments could be equally good.

46. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process For ethical reasons, if during a clinical trial one treatment is clearly shown to be superior to the comparison treatment, the independent data monitoring and safety committee will recommend that the trial be stopped. The better treatment is then offered to patients with the health problem in question.

47. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary The clinical trial process Patients should only enroll in a clinical trial after having clearly understood the benefits and adverse effects they might experience. It is essential that patients are given clear information before deciding whether to participate.

48. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Informed consent

49. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Informed consent Informed consent should give you all the important information about the clinical trial to help you decide whether to enroll.

50. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Informed consent As a first step, every potential participant meets one of the clinical trial researchers, who will explain the possible benefits and risks of participating.

51. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Informed consent After the meeting, the researcher will give you detailed written information about the clinical trial to help you consider whether to participate. If you decide to enroll in the study, you will be asked to sign and date an informed consent declaration. You always have the right to decline an invitation to take part in a clinical trial.

52. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Informed consent Informed consent ensures that nobody enrolls in a clinical trial without having received detailed information and having personally consented to take part. TrueFalse

53. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Informed consent Informed consent ensures that nobody enrolls in a clinical trial without having received detailed information and having personally consented to take part. TrueFalse Correct! The consent process protects the patient‘s right to receive information and ensures the informed consent to participate in a clinical trial.

54. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Informed consent Informed consent ensures that nobody enrolls in a clinical trial without having received detailed information and having personally consented to take part. TrueFalse Incorrect! The consent process protects the patient‘s right to receive information and ensures the informed consent to participate in a clinical trial.

55. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Informed Consent When you are participating in a clinical trial, you will be updated periodically with relevant information which could influence your decision to remain in the trial. Informed consent does not obligate you to remain in the clinical trial. You can leave the clinical trial at any time without giving any explanation!

56. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Informed Consent Once a participant has signed the informed consent form, it is not possible to leave the clinical trial anymore. TrueFalse

57. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Informed consent Once a participant has signed the informed consent form, it is not possible to leave the clinical trial anymore. TrueFalse Correct! Participation is voluntary and you can quit at any time.

58. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Informed consent Once a participant has signed the informed consent form, it is not possible to leave the clinical trial anymore. TrueFalse Incorrect! Despite signed informed consent, you can quit a clinical trial at any time.

59. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Informed consent You should ask the study team any questions or doubts you may have about the clinical trial. It is essential that you understand the key statements in the informed consent document about the treatments and their possible benefits and risks.

60. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary What protection do you have as a participant in a clinical trial?

61. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Patient safety The basic ethical principles and legal codes which govern medical practice also apply to treatments given in clinical trials! In addition, to protect trial participants, clinical trials are governed through further international guidelines and legislation.

62. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Patient safety Before a clinical trial can start, it is checked for patient safety and scientific content by an ethics committee and (for drug trials) other competent authorities. All good studies undergo strict quality control.

63. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Patient safety Results from clinical trials should be made public at scientific conferences and in journals, and reported to relevant authorities. The identity of trial participants remains confidential.

64. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Patient Safety It is standard practice to keep the names of clinical trial participants secret. TrueFalse

65. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Patient safety It is standard practice to keep the names of clinical trial participants secret. TrueFalse Incorrect! The names of trial participants must not be revealed!.

66. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Patient safety It is standard practice to keep the names of clinical trial participants secret. TrueFalse Correct! It is standard practice in clinical trials that names of participants will not be disclosed.

67. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Where can I find clinical trials? -Trials Registers -

68. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Trials Registers If you are looking for a particular clinical trial you can ask your doctor. In addition you can search the following websites: WHO International Clinical Trials Registry Platform at http://www.who.int/ictrp/en/ http://www.who.int/ictrp/en/ US National Institutes of Health at http://clinicaltrials.gov/ http://clinicaltrials.gov/ The ISRCTN at http://www.controlled- trials.com/ukctr/http://www.controlled- trials.com/ukctr/ The EU Clinical Trials Register at www.clinicaltrialsregister.eu www.clinicaltrialsregister.eu The website of your national health service, e.g., the UK National Health Service http://www.nhs.uk/Conditions/Clinical- trials/Pages/clinical-trialaspx/

69. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Trials Registers Registers contain public information about clinical trials, such as venues, aims, designs and patient selection criteria. Trial registers should also contain contact information for patients interested in participating.

70. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary

71. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary A controlled clinical trial is conducted to test new or existing treatments on patients. Clinical trials should have well defined aims and methods, which are described in detail in trial protocols.

72. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Controlled clinical trials are the most reliable and safest way to assess whether new treatments are better than standard treatments. Proposals for clinical trials must be assessed and authorised by ethics committees and other competent authorities.

73. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary Participating in clinical trials is always voluntary. You can quit a clinical trial at any time – despite having signed an informed consent document. Your personal rights and data are protected.

74. Introduction Clinical trials Why clinical trials? The Clinical Trial Process Informed consent Patients‘ interests Rights and protection Trials Registers Summary We hope you liked this short tutorial and found it useful. Keep exploring the ECRAN website and learn even more about clinical trials! Thank you for your kind attention!