Introduction

1. Clinical trials Introduction

2. 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 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 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 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. What are controlled clinical trials?

7. 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. 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. 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. 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. What are clinical trials? Controlled clinical trials conducted on large numbers of patients are essential for assessing the efficacy and safety of new treatments. True False

12. What are clinical trials? Controlled clinical trials conducted on large numbers of patients are essential for assessing the efficacy and safety of new treatments. True False Your choice is correct!

13. What are clinical trials? Controlled clinical trials conducted on large numbers of patients are essential for assessing the efficacy and safety of new treatments. True False Your choice is not correct!

14. What are clinical trials? New treatments that have been tested in a laboratory have no risks whatsoever when used in clinical trials. True False

15. What are clinical trials? New treatments that have been tested in a laboratory have no risks whatsoever when used in clinical trials. True False Correct! Laboratory tests help designing new treatments but cannot reveal risks for patients.

16. What are clinical trials? New treatments that have been tested in a laboratory have no risks whatsoever when used in clinical trials. True False Wrong! New treatments can always have unknown and unpredictable risks.

17. Why are controlled clinical trials important?

18. 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. Why are clinical trials important? Clinical trials aim to enhance new or existing treatments and diagnostic strategies.

20. Why are clinical trials important? Clinical trials are important because they investigate and compare new and existing treatments, thus promoting progress in treatment.

21. Are you considering enrolling in a clinical trial?

22. 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. 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. 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. 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. Enrolling in a clinical trial? The results of clinical trials always represent an improvement of the standard available treatment. True False

27. Enrolling in a clinical trial? The results of clinical trials always represent an improvement of the standard available treatment. True False 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. Enrolling in a clinical trial? The results of clinical trials always represent an improvement of the standard available treatment. True False Yes! But new interventions are only very slightly more likely than not to prove better than standard treatments.

29. 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. True False

30. Enrolling in a clinical trial? Researchers conducting a clinical trial hope that their new treatment is better than the standard one already available. True False Your choice is not correct! Reseachers always conduct a clinical trial in the hope of improving treatment

31. Enrolling in a clinical trial? Researchers conducting a clinical trial hope that their new treatment is better than the standard one already available. True False Correct! Although disappointment is possible, researchers always hope to achieve an improvement

32. The clinical trial process

33. 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. 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. 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. 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. 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. 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. 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. The clinical trial process When testing a new treatment, controlled clinical trials must give priority to protecting patients‘ safety and wellbeing. True False

41. The clinical trial process When testing a new treatment, controlled clinical trials must give priority to protecting patients‘ safety and wellbeing. True False Correct!

42. The clinical trial process When testing a new treatment, controlled clinical trials must give priority to protecting patients‘ safety and wellbeing. True False Incorrect! Clinical trials are first and foremost committed to patients‘ safety and only secondarily to scientific results.

43. The clinical trial process The control group always receives the less effective treatment. True False

44. The clinical trial process The control group always receives the less effective treatment. True False 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. The clinical trial process The control group always receives the less effective treatment. True False 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. 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. 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. Informed consent

49. Informed consent Informed consent should give you all the important information about the clinical trial to help you decide whether to enroll.

50. 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.