 A test of a new intervention or treatment on people

 To allow medical professionals and patients gain information about the benefits, side effects and possible uses of new drugs as well as new ways to use existing drugs  To translate results of basic scientific research into better ways to prevent, diagnose, or treat cancer

 We need to know that any treatments we recommend are both safe and effective in humans  Cell culture and animal work can only take us so far!  Especially in Oncology, people are always looking for the miracle cure-and it is easy to get dragged into the idea  Scientific, medical, evidence-based paradigm

 Treatment trials  Prevention trials  Early-detection trials/screening trials  Diagnostic trials  Quality-of-life studies/supportive care studies  Genetic trials

 It can be a phase I, II or III trial  It can be randomized or not  It can be blinded or not  It can involve a placebo or not  It can be a pilot study or not

◦ people ◦ Determines  what dose is safe  How the treatment should given  How the treatment affects the body  Safety (the safest dose)

◦ Less than 100 people ◦ Determines  Whether the treatment does what it is supposed to  How the treatment affects the body  If the drug or intervention has an effect on the cancer  Does not compare with other treatments

◦ From 100 to thousands of people ◦ Equal chance to be assigned to one of two or more groups (randomization) ◦ Determines  How the new treatment compares with the current standard  Or how it compares with placebo

◦ From hundreds to thousands of people ◦ Usually takes place after drug is approved to provide additional information on the drug’s risks, benefits and optimal use ◦ Post marketing surveillance.

Equal chance to be assigned to one of two or more groups Equal chance to be assigned to one of two or more groups One gets the most widely accepted treatment (standard treatment) One gets the most widely accepted treatment (standard treatment) The other gets the new treatment being tested, which researchers hope and have reason to believe will be better than standard treatment The other gets the new treatment being tested, which researchers hope and have reason to believe will be better than standard treatment All groups are as alike as possible All groups are as alike as possible Provides the best way to prove the effectiveness of a new agent or intervention Provides the best way to prove the effectiveness of a new agent or intervention

Control Group Investigational group

 Open Label clinical trials ◦ The doctor and patient know which drug or vaccine is being administered  Blinded clinical trial ◦ Single Blind: the patient doesn’t know which treatment he/she is getting ◦ Double Blind: neither doctor nor patient knows

 The new treatment is tested against an inactive (or dummy) treatment that looks the same

 A small study that helps develop a bigger study  A first foray (look) into a particular area  Used to iron out possible difficulties, and help with design of the bigger, more pivotal study.

◦ Involve people who are sick ◦ Test new treatments, new combinations of drugs or new approaches to surgery or radiotherapy ◦ Determine the most effective treatment for people who have cancer ◦ Test safety and effectiveness of new agents or interventions in people with cancer

◦ Evaluate the effectiveness of ways to reduce the risk of disease or prevent the recurrence of disease ◦ Enroll healthy people at high risk for developing disease ◦ Assess new means of detecting disease earlier in healthy people

 Early-detection trials/screening trials ◦ Test the best way to detect early disease,  Pap smears, Mammograms  Blood tests, X-rays ◦ Detect disease at an earlier stage, resulting in improved outcomes  Diagnostic trials ◦ Develop better tools for classifying types and phases of disease and managing patient care ◦ Usually include people who have signs or symptoms

 Quality-of-life/supportive care studies ◦ Aim to improve comfort and quality of life for patients and their families  Genetic trials ◦ Determine how one’s genetic makeup can influence detection, diagnosis, prognosis, and treatment ◦ Broaden understanding of causes of disease ◦ Develop targeted treatments based on the genetics of a disease

 Clinical research team check the health of the participant at the beginning of the trial, give specific instructions for participating in the trial, monitor the participant carefully during the trial, and stay in touch after the trial is completed. ◦ Tests ◦ Doctors visits ◦ Frequent follow up

All clinical trials have guidelines about who can participate. Exclusion / inclusion criteria help produce reliable results Criteria based on factors such as Age / Gender Age / Gender Type and stage of disease Type and stage of disease Previous treatment Previous treatment Medical conditions Medical conditions

Physicians and other health professionals may: ◦ Be unaware of appropriate trials ◦ Be unwilling to lose control of patient’s care ◦ Believe that standard therapy is best ◦ Believe that clinical trials are more work ◦ Have concerns about the patient’s care or how the person will react to suggestion of clinical trial participation

Patients may: ◦ Be unaware of clinical trials ◦ Lack access to trials ◦ Fear, distrust, or be suspicious of research ◦ Have practical or personal obstacles ◦ Be unwilling to go against their physicians’ wishes

 At a minimum, the best standard treatment  Early access to new treatments. If the new treatment or intervention is proven to work, patients may be among the first to benefit  Participation in advancing medical knowledge. Patients have a chance to help others and improve cancer care  Active role in own health care  The medical team conducting the trial will carefully and regularly monitor the patient’s progress

◦ New treatments or interventions under study are not always better than, or even as good as, standard care ◦ Even if a new treatment has benefits, it may not work for every patient ◦ Unpleasant, serious or even life threatening side effects ◦ May require more time and attention than a non- protocol treatment

 Ethical and legal codes that govern medical practice also apply to clinical trials  Informed consent  Review boards ◦ Scientific review ◦ Institutional review boards (IRBs) ◦ Data safety and monitoring boards

 Informed consent is a document designed to inform the patient of the purpose and design of a clinical study, possible side effects and benefits and if there are any other options. It should also include information on ◦ voluntary participation ◦ Duration of trial ◦ Insurance and compensation ◦ Name and phone number of contact person ◦ Procedures ◦ Individual rights and confidentiality

 Scientific review ◦ Panel of experts  Institutional review boards (IRBs) ◦ Qualified people to evaluate new and ongoing trials ◦ All institutions that conduct clinical trials must, by law, have a IRB that approves the protocol  Data and safety monitoring boards:  Ensure that risks are minimized  Ensure data integrity  Stop a trial if safety concerns arise or objectives have been met

 Yes, in general they are.  We (the scientific community) strive to make them so.  There are unscrupulous people (and companies) in any area  Guidelines make it easier for us to check up on ourselves!

 Yes (usually)  There are stringent guidelines in place  Safety and toxicity are closely monitored  Trials have built-in stopping rules  Subjects are indemnified

 The Declaration of Helsinki  GCP guidelines  Transparency and good communication  Use of Institutional Ethics committees

 Consider the question I want to answer  Write a draft protocol  Decide if it is a phase I, II, III or pilot study  Write the Ethics Committee application  Submit that  Work out where funding will come from

A wide variety of clinical trials are performed. These include phase I/II and III studies of new drugs, and ongoing program in supportive care and psychosocial research

 A study plan on which all clinical trials are base (recipe or blueprint)  Provides background about the trial  Describes trial’s design and organization  Ensures that trial procedures are consistently carried out  Each study enrolls people who are alike in key ways

 Sponsor can be ◦ Pharmaceutical company ◦ Co-operative group (NHMRC, TROG, NSABP) ◦ Another Investigator ◦ Foundation  Responsibilities of the sponsor ◦ update available data ◦ liaise with the appropriate regulatory bodies ◦ communication between trial centre and sponsor ◦ monitoring trial at the site ◦ ensuring all data collected

 Profile ◦ Adequate qualifications to conduct research in a given area ◦ Necessary resources ◦ Sound knowledge of the investigational drug and protocol ◦ Sound knowledge of GCP  Responsibilities ◦ training of staff ◦ ethics submission ◦ facilities and equipment ◦ resources for data collection ◦ informed consent ◦ reporting of serious adverse events

 Patient education  Emotional support  Management of side effects  Source documentation ◦ Vital signs ◦ Adverse events - CTC ◦ Protocol deviations ◦ ECOG Performance status

 Responsible for the collection, handling, manipulation, tracking and quality of the data.  Ensure ◦ clinicians adhere to the protocol, ◦ trial patients receive the therapy dictated by the protocol,  provide support to the patients  All in accordance with Good Clinical Practice (GCP)

 What is the purpose of the study?  Why do researchers believe the new treatment being tested may be effective?  What kinds of tests and treatments are involved?  How do the possible risks, side effects, and benefits in the study compare with my current treatment?  How long will the trial last?  Who will pay for the treatment?  How will I know that the treatment is working?  Can I leave the study after it has begun?

 Oncologist  NCI Web site  NHMRC Web site  National Breast Cancer Centre  RAH Cancer Centre