WHY SHOULD I JOIN A CLINICAL TRIAL?

Dawn Hershman, MD, MS

Associate Professor of Medicine and EpidemiologyLeader, Breast Caner ProgramHerbert Irving Comprehensive Cancer CenterColumbia University Medical Center

NCI Community Oncology Research ProgramSWOG – Research Base Co-PI

What is a clinical trial?

• Clinical trials look at new ways to prevent, detect, control or treat disease.

• The GOAL is to find if a new test or therapy is safe and effective.

• It is important to have many types of people with different ages, races, ethnicities, and genders to see how different people respond to a treatment

http://www.nih.gov/health/clinicaltrials/basics.htm

What is a clinical trial?

• Participants are assigned to receive one or more interventions (or no intervention)

• Researchers evaluate the effects of the interventions on biomedical or health-related outcomes.

• The assignments are determined by the study protocol.

• Participants may receive a drug, treatment, procedure, or other types of interventions.

http://clinicaltrials.gov/ct2/about-studies/glossary#C

Clinical Research Categories

• Interventional

• Observational

• Ancillary

• Correlative

Interventional

• Individuals are assigned to receive intervention

• Drug, Device or Other (ie behavioral)• Diagnostic, Therapeutic, Supportive Care• Assignment may or may not be random• Participants are followed and a health

outcome is assessed

Observational

• Involves no intervention or alteration of the status of the participant

• Biomedical or health outcomes are assessed in a pre-defined group of participants

• Participants may or may not receive the intervention

• The investigator is not responsible for assigning the specific intervention

Observational Studies vs. RCTs

Armstrong, K, JCO 2012;30: 4208-42144

Strengths Observational Studies

• Examine “real world” populations– Diversity increases generalizability

• Large numbers of participants• Leverage existing data• Includes vulnerable populations• Power to find a dose response relationship• Can be completed more quickly with less

cost

Limitations of Observational Data

• Selection Bias• Systematic error in the ascertainment of study subjects

• Intervention groups differ in characteristics that are associated with the outcome of interest

• Performance Bias• The delivery of one type of intervention is associated with

generally higher levels quality of care

• Detection Bias• Outcomes of interest are more easily detected in one

group than another

Ancillary/Correlative

• Ancillary– Stimulated by a main clinical trial to answer

secondary question– Includes patients accrued to the main study

• Correlative– Laboratory based– Use specimens that exist– Used to assess risk, outcomes, response

What are the types of clinical trials?

Diagnostic: Protocols designed to evaluate interventions aimed at identifying a disease or health condition

Prevention: Protocols designed to assess interventions aimed at preventing the development of a disease or health condition

Screening: Protocol designed to examine methods for identifying a condition or risk of a condition in people not known to have the condition

http://www.nih.gov/health/clinicaltrials/basics.htm

What are the types of clinical trials?

Treatment: Protocol designed to evaluate interventions for treating a disease

Supportive Care: Protocol designed to evaluate interventions to maximize comfort, minimize side effects or prevent the decline in a health condition

Health Care Deliver: Protocol designed to evaluate the delivery, processes, management, organization or financing of healthcare

http://www.nih.gov/health/clinicaltrials/basics.htm

Clinical trial stages

Pre-clinical stage

• A new drug or treatment is tested using animals to determine if it is safe for humans

Phase I

A new treatment is tested in a small number of people to see how safe it is

and what are its side effects

Involves 20-80 subjects

Phase II

A treatment is given to a larger number of people to see its effectiveness and safety

Involves 100-300 people

Phase III

A treatment is tested in large number of people to prove that it is effective, check

side effects, compare it to other treatments and get safety information

Involves 1,000-3,000 people

Phase IV

A treatment is now approved by the FDA and available to the public but its usage,

risks and benefits are still monitored

What is a clinical protocol?

• Studies are led by investigators who write the study protocol

• Protocols describe: – Who can participate – The length of the study– What they will receive – What information is collected

http://www.nih.gov/health/clinicaltrials/basics.htm

What is a clinical protocol?

Eligibility criteria are an important part of the protocol

• Criteria often include: – Age – Gender Often not everyone– Type of disease meets criteria for– Stage of disease participation– Previous treatment– Medical conditions

http://www.nih.gov/health/clinicaltrials/basics.htm

How does a clinical protocol become approved?

• Once an idea is formulated and the protocol written it must be reviewed

• All clinical trials in the US are approved and monitored by an Institutional Review Board (IRB)

http://www.nih.gov/health/clinicaltrials/basics.htm

What is an IRB?

An IRB is an independent committee of doctors, statisticians, and community members who review a study’s safety,

human rights, and ethics

Informed consent

Informed consent • Understanding the procedures involved,

risks and benefits of a study are extremely important when making decisions

• The informed consent document and discussion are used to help you in this process

• Translation and interpretive services are available during this time

http://www.nih.gov/health/clinicaltrials/basics.htm

Clinical trial concepts• Placebo: Inactive product that is very similar to

the real drug or treatment but does has no affect on the condition

• Randomization: A person is randomly assigned to one of any treatments in a study. Done to avoid bias or influence on the outcome

• Single or double blinding: the subject doesn’t know the treatment (single) the subject and researcher do not know the treatment (double)

http://www.nih.gov/health/clinicaltrials/basics.htm

What happens once the clinical trial is over?

• Analysis: All collected information is analyzed to see if there are any differences between treatment groups

• Peer review: Experts review the analysis to see it is sound

• Publication: Once it is past peer review it is published in a scientific journal

http://www.nih.gov/health/clinicaltrials/basics.htm

Why should I take part in a clinical trial?

1. Access to a new intervention that’s not normally available.2. A new intervention may improve your health.3. Most studies cover the cost of the intervention.4. You are helping researchers answer questions about a disease.5. You play an active role in your own health care.

1. A new intervention may not be better than the standard.2. A new intervention has risks and side effects.3. Your health insurance may not cover all costs.4. If you are in a randomized study you will not be able to choose the intervention you receive.5. You may need to make more visits to the clinic or hospital.

NCI Clinical Trials

• NCTN – National Clinical Trials Network

• NCORP -NCI Community Oncology Research Program

NCI Supports Community-Based Cancer Research

• Majority of cancer care is provided in the community

• Access to large diverse patient populations

• Access to real world healthcare delivery settings

• Test feasibility of new interventions/processes

• Engage community oncologists in the research process to accelerate the uptake of evidence-based practice

NCTN

NCI Funding for NCTN

NCORP Research Expansion

Cancer Prevention, Control and Screening/Post-Treatment SurveillanceClinical Trials and HRQOL Studies

Treatment and Imaging Clinical Trials

Minority/Underserved Accrual

Cancer Care

DeliveryResearch

Division of CancerControl and PopulationSciences (DCCPS)

NCORP Associate Director

Center to Reduce Cancer Health Disparities (CRCHD)

Division of CancerTreatment and Diagnosis (DCTD)

Division of Cancer Prevention(DCP)

NCORP Director

NCORP Organizational StructureNCI

NCORPResearch Bases:NCTN GroupsCancer Centers

Cancer Prevention and Control Trials

Cancer Care Delivery

Community Sites:NCORPNCORP-Minority/

UnderservedCancer Prevention

and Control TrialsTreatment TrialsCancer Care

DeliveryExtramural InvestigatorsNCI-designated Cancer CentersOther Academic CentersHealth Care OrganizationsNonprofit Research

Organizations

Clinical Trials and Translational Research Advisory Committee (CTAC)

Coordinating Centerfor Clinical Trials

Evaluation and Prioritization of Research Concepts

Steering Committee:Disease specificSymptom mgt./QOLCancer Care Delivery

CentralInstitutionReviewBoard

CIRBCancerTrialsSupportUnit

CTSU

National ClinicalTrials Network(NCTN)

Treatment Trials

Cancer prevention trials

TARGET = Prevent breast cancer recurrence OR prevent breast cancer

• DHA or placebo to prevent recurrence in breast cancer survivors

• Vitamin D or placebo in premenopausal women at high risk for breast cancer

• BFIT: 1st degree female relatives of breast cancer survivors receive an educational intervention

Cancer treatment trials

FOCUS = Receive intervention before

OR after surgery

• Receive propanolol prior to breast surgery to determine its effect on tumor growth

• Receive metformin and atorvastatin prior to breast surgery to determine its effect on tumor growth

Cancer treatment trials

FOCUS = Receive intervention before

OR after surgery• (B47) Randomly receive 1 of 4 chemotherapies

after surgery • (B50) Receive a drug called TDM1 or Herceptin if

breast disease is still present after surgery and received treatment prior to surgery

• (S1207) Receive a drug called everolimus for high risk hormone positive and HER2 negative disease

Metastatic treatment trials

FOCUS = Receive intervention to prevent disease proliferation

• Triple negative breast cancer patients: metformin and erlotinib

• Metastatic patients with hormone sensitive Her2 Negative. Letrozole +/- palbocyclib

Metastatic treatment trials

• Metastatic Her-2 positive randomized to lapatinib + Xeloda vs. Neratinib + Xeloda

• Bollero 4 – everolimus/letrozole +/- RAD Y24135

• LY2835219 – hormone sensitive her-2 negative

• PD-L1 – Phase 1

• Her2 + - trastuzumab/ruxolitinib

Symptom management trials

FOCUS = Receive intervention to address side effects

• True, sham or no acupuncture to treat joint pain caused by hormonal therapy

• True or sham electroacupuncture to treat numbness during taxol chemotherapy

• Menthol cream or placebo to treat numbness after chemotherapy

Cancer survivorship trials

FOCUS = Gather information on the physical & mental health of survivors

• Exercise and Dietary intervention to decrease weight and improve outcome

How do I find out about trials?

• ONCOLOGISTS– ASK YOUR ONCOLOGIST - They are familiar with

clinical trials resources, websites, and contacts

• COMMUNITY RESOURCES– Local support groups– American Cancer Society

• INTERNET– All trials are registered in the US and worldwide on

clinicaltrials.gov

• FRIENDS & FAMILY