IMPROVING CANCER CARE

THROUGH CLINICAL TRIALSJessica Rhee, MD

Medical Director, Clinical Trials Office

Overview

• Definitions/terms

• Clinical trials basics

• Importance of clinical trials

• Role of UH Cancer Center

• Dispelling myths

• High impact trials

Definition by NIH: Clinical Trial

Research study that prospectively assigns human subjects to interventions to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes

Definition: Intervention

Manipulation of subject or subject’s environment for purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints

Intervention: Examples

• Drugs/compounds

• Devices (prosthesis)

• Procedures (surgical techniques)

• Health delivery systems (telemedicine)

• Strategies to change health-related behavior (diet, cognitive therapy, exercise)

• Other strategies: treatment, prevention, diagnosis

Key Stakeholders for Clinical Trials

• Patients → families, caretakers, support system

• Community healthcare providers

• Hospitals/healthcare systems

• Insurers

• Government agencies

• Academic Cancer Centers

Types of Cancer Clinical Trials

• Treatment

• Prevention

• Screening

• Supportive Care

• Correlative (laboratory science)

• Healthcare Delivery

• Diagnostic

• Quality of Life

Treatment Trials

• Safe dose of new treatment?

• How should new treatment be given?

• Does new treatment prolong life?

• Improve quality of life?

• New treatment’s side effects?

• Prevent cancer from spreading or returning?

Funding of Clinical Trials

• National Institutes of Health (NIH) – largest federal funder of clinical trials in U.S. ($3 billion/yr)

• Department of Defense

• Department of Veterans Affairs

• Private industry: – Pharmaceutical/biotech companies

– Medical institutions

– Private foundations

Phases of Cancer Clinical Trials

(15-30) (<100) (100 tothousands)

* *

* FDA-approval

How Do Cancer Clinical Trials Work?

• Participants assigned to specific study group

• Level of medical attention and care same regardless of study group assigned

Study population

Standard Treatment

+Placebo

Standard Treatment

+Investigational

drug

Assess responseAssess response

Compare responses

Use of Placebos

• Product designed to look like the investigational agent being tested, but is not active

• Rarely used in cancer treatment clinical trials:

– no standard treatment

– comparing standard treatment plus a placebo vs. standard treatment plus new treatment

• Helps prevent bias in research

• Participants always told if study uses placebo

• Process of assigning participants to different study groups by chance alone → prevent bias

• Some phase 2 trials

• All phase 3 trials

Who Can Participate?• Guidelines for participation

• Inclusion criteria → factors that allow volunteers to participate

• Exclusion criteria → factors that disallow volunteers from participating

• Examples: age, gender, type/stage of disease, prior treatments, other medical conditions

• Reason for criteria• Identify appropriate participants

• Promote participants' safety

• Ensure researchers learn the information they need

Patient Safety

• Federal laws ensure safety and ethics

• Protected by:

– Informed consent process

– Review and approval by scientific experts and institutional review board (IRB)

– Ongoing monitoring of trial

Rights of Participants

• Told purpose of clinical trial

• Told all potential risks, side effects, discomforts

• Told any benefits reasonably expected

• Told what will happen; whether any interventions are different from standard medical care

• Told all options available

Rights of Participants• Allowed to ask questions any time

• Allowed ample time, without pressure, to make decision to participate

• Can refuse to participate, for any reason, before and after the trial has started

• Receive signed copy of informed consent form

• Told of any treatments available if complications occur during the trial

Good Clinical Practice (GCP)

• Principle put in place to help assure the safety, integrity, and quality of clinical trials

• Constitutes international ethical and scientific quality standard for designing, conducting, recording, and reporting clinical trials

• 1/1/17 →GCP training required of all NIH-funded clinical investigators and clinical trial staff

Informed Consent

• Process to help volunteers decide whether or not to participate in a clinical trial

• Every volunteer has the right to know and understand what will happen during the clinical trial

Research Team

• Principal investigator

• Research nurse

• Clinical research associate

• Data specialist

• Treating physician and nurse

Clinical Trial Participation Costs

• Routine care costs: charges for treatment even if not enrolled on clinical trial

– doctor visits

– hospital stays

– laboratory/imaging tests

– standard treatments

Clinical Trial Participation Costs

• Research costs: related to taking part in clinical trial

– investigational drug

– extra doctor visits

– tests performed solely for research purposes

Clinical Trial Participation Costs

• 2014: ACA requires all health insurers to pay for routine care for people participating in approved, federally funded clinical studies for cancer and other life-threatening diseases (excludes Medicaid)

Importance of Clinical Trials

• Research brings hope for cures →key to making progress against cancer

• Today’s treatments were clinical trials 5-10 years ago

• Today’s clinical trials may be standard treatments in 5-10 years

Benefits of Clinical Trials• Access to new and novel treatments

and approaches

• Contribute to cancer research

• Highest quality of care

– Increased oversight

– Standardized, scientifically reviewed treatments

– Mandatory quality assurance

Cancer Clinical Trials Statistics

• Children → 70-75% of kids with cancer enroll onto clinical trial

• Adults → ~3% of adults with cancer enroll onto clinical trial for treatment

• Reasons:

– Lack of knowledge/education

– Concerns about effectiveness

– Concerns about cost

Clinical Trials Lack Ethnic Diversity

• 80-95% clinical trials participants Caucasian

• Under-representation of racial/ethnic minorities

• Reduces generalizability of research findings

Hawaiʻi population

NCCN Guidelines• National Comprehensive Cancer Network

• Recommendations/algorithms: prevention, diagnosis, management of cancer

”Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.”

UH Cancer Center

• 70 NCI-Designated Cancer Centers• Forefront of NCI-supported efforts• Scientific leadership, resources,

depth/breadth research• Significant impact → improve

cancer care and quality of life• Infrastructure, coordination,

scientific/quality oversight• Disease-focused specialists

HI

UHCC Public Education Campaign

Dispelling Myths

Myth: only for advanced cancer when no other

treatments available

Fact: all stages of cancer, prevention, diagnosis

Myth: Participants treated like guinea pigs

Fact: • Many measures to protect participants

• Scientific oversight (IRB, FDA)

• Strict guidelines ensure ethical treatment

• Patient Rights: informed consent, right to withdraw anytime

• Participant surveys: respectful treatment; care exceeded expectations; participate again; recommend to others

Myth: Clinical trials are dangerous because they use new medicines and practices

Fact: • Clinical trials designed for research so some level of

risk

• Investigational drugs go thru rigorous testing and scientific evidence for safety/efficacy in humans

• Participants monitored closely for adverse effects

Myth: Participation provides no benefit to me

Fact: Access to latest treatments/procedures;

outcomes at least as good, if not better, than standard care

• Myth: I can’t drop out of study without

jeopardizing quality of my treatment

• Fact: May quit anytime for any reason; same high

quality care and monitoring continues

• Myth: If there is a clinical trial that might help

me, my doctor will tell me about it

• Fact: – Doctor may not know about all available clinical trials that

might benefit you

– Clinical trials may not be priority for doctor

– Doctor might have bias against clinical trials

High-impact national trials available locally through UH Cancer Center

June 3, 2018DOI: 10.1056/NEJMoa1804710

Herceptin story

Take Home Message

• Best treatment option for cancer patients is a clinical trial

• Clinical trial participants receive highest level of care

• Most adult cancer patients do not enroll due to multitude of barriers at all levels – most can be overcome

• Clinical trials benefit participants, society, science

There is no CURE without U

Questions?