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

◦ 15-30 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 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

1

3

79

10

8

2 4

5

6

24

5 6

13

7

9 10

8 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 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

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

Thank you