The Basics of Clinical Trials

Dorothy M K Keefe MD FRACPChairman Cancer Research Advisory CommitteeCancer Council South Australia

What is a Clinical trial?

A test of a new intervention or treatment on people

Why are Clinical Trials conducted in Cancer? To allow medical professionals and patients

to 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

Why do we need them?

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

Types of Clinical Trials

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

studies Genetic trials

Types of clinical trial

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 And it can be a pilot study or not

Phase I

15-30 people Determines

what dose is safe How the treatment should given How the treatment affects the body safety

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

Phase II

From 100 to thousands of people Equal chance to be assigned to one of two

or more groups Determines

How the new treatment compares with the current standard

Or how it compares with placebo

Phase III

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

Phase IV

Randomised Clinical Trials

Equal chance to be assigned to one of two Equal chance to be assigned to one of two or more groupsor more groups One gets the most widely accepted One gets the most widely accepted

treatment (standard treatment)treatment (standard treatment) The other gets the new treatment being The other gets the new treatment being

tested, which researchers hope and tested, which researchers hope and have reason to believe will be better have reason to believe will be better than standard treatment than standard treatment

All groups are as alike as possible All groups are as alike as possible Provides the best way to prove the Provides the best way to prove the

effectiveness of a new agent or effectiveness of a new agent or interventionintervention

Randomisation1

3

79

10

8

2 4

5

6

24

5 6

13

7

9 10

8 Control Group

Investigational group

Open versus Blinded Clinical Trials

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

Placebo control

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

Pilot Study

A small study that helps develop a bigger study

A first foray into a particular area Used to iron out possible difficulties,

and help with design of the bigger, more pivotal study.

Involve people who have cancer 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

Treatment Trials

Evaluate the effectiveness of ways to reduce the risk of cancer or prevent the recurrence of cancer

Enroll healthy people at high risk for developing cancer

Assess new means of detecting cancer earlier in healthy people

Prevention Trials

Early-detection trials/screening trials Test the best way to detect early cancer,

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 cancer and managing patient care Usually include people who have signs or

symptoms

Early detection/screening/diagnosis

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 cancer Develop targeted treatments based on the

genetics of a tumor

What happens in a clinical trial? 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

Who can participate in clinical trials? All clinical trials have guidelines about who All clinical trials have guidelines about who can participate. Exclusion / inclusion can participate. Exclusion / inclusion criteria help produce reliable results criteria help produce reliable results Criteria based on factors such asCriteria based on factors such as

Age / GenderAge / Gender Type and stage of diseaseType and stage of disease Previous treatmentPrevious treatment Medical conditionsMedical conditions

Do Many People Participate in Cancer Clinical Trials?

Less than 5% of Adults with cancer participate in clinical trials

Barriers to Participation in Clinical TrialsPhysicians 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

Barriers to Participation in Clinical Trials

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

Benefits of Participation in Clinical Trials

Risks of Participation in Clinical Trials

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

How Are Patients’ Rights Protected?

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 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

Review boards 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

Are they Ethical? 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!

Dr James will discuss

Are they safe?

Yes (usually) There are stringent guidelines in place Safety and toxicity are closely

monitored Trials have built-in stopping rules Subjects are indemnified

How can we tell they are done properly?

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

So what do I personally do if I have an idea for a trial?

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

RAH Cancer Centre Clinical Trials

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

The Protocol

A study plan on which all clinical trials are base (recipe or blueprint)

Provides background about the trial Describes trial’s design and organisation Ensures that trial procedures are consistently

carried out Each study enrolls people who are alike in key

ways

The Sponsor 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

The Investigator

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

The Clinical Trials Nurse

Patient education Emotional support Management of side effects Source documentation

Vital signs Adverse events - CTC Protocol deviations ECOG Performance status

The Clinical Trial Coordinator or Data Manager 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 should you consider before joining a clinical trial 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?

How do you find out about Clinical Trials? Oncologist NCI Web site www.cancer.gov NHMRC Web site www.ctc.usyd.edu.au National Breast Cancer Centre www.nbcc.org.au RAH Cancer Centre

www.rah.sa.gov.au/cancer/medical1.php