Including Clinical Trials

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Contents

Module 1: Becoming an Investigator: Considerations ................................................................... 8

Including Clinical Trials in Your Practice ..................................................................................... 8

Becoming an Investigator ........................................................................................................... 8

Investigator Benefits ................................................................................................................... 9

Patient Benefits ........................................................................................................................... 9

Patient Safeguards .................................................................................................................... 10

Changes to Your Practice .......................................................................................................... 10

Why become an investigator .................................................................................................... 12

Investigator Responsibilities ..................................................................................................... 13

What you can offer ................................................................................................................... 14

Module 1 Quiz ........................................................................................................................... 14

Module 1 Summary ................................................................................................................... 16

Module 2: Initial Site Preparation ................................................................................................. 17

Initial Considerations ................................................................................................................ 17

Ways to Participate in Trials ..................................................................................................... 18

NCIs Clinical Trials Cooperative Groups ................................................................................... 18

NCIs Community Clinical Oncology Program (CCOP) ............................................................... 18

NCIs Cancer Trials Support Unit (CTSU) ................................................................................... 19

NCIs Cancer Centers Program .................................................................................................. 19

Private Industry-sponsored Trials ............................................................................................. 19

Identifying an IRB of Record ..................................................................................................... 20

Identifying an IRB of Record ..................................................................................................... 21

The NCI CIRB ............................................................................................................................. 21


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The NCI CIRB Process ................................................................................................................ 21

The NCI CIRB Process ................................................................................................................ 21

Registering with the FDA: The 1572 Form ................................................................................ 22

1572 Form Commitments ......................................................................................................... 22

Additional Requirements .......................................................................................................... 24

Quiz ........................................................................................................................................... 25

Module 2 Summary ................................................................................................................... 26

Module 3: Choosing the Trial(s) .................................................................................................... 27

Choosing a Specific Trial............................................................................................................ 27

Factors to Consider ................................................................................................................... 27

Processes to Assist Trial Selection ............................................................................................ 28

Established Forms and Procedures ........................................................................................... 29

Funding and Reimbursement ................................................................................................... 29

Startup and Ongoing Expenses ................................................................................................. 30

Sponsor Reimbursement .......................................................................................................... 30

Insurance Reimbursement ........................................................................................................ 30

Medicare Coverage ................................................................................................................... 32

Local Institution Support ........................................................................................................... 33

Module 3 Quiz ........................................................................................................................... 33

Module 3 Summary ................................................................................................................... 35

Module 4: Building and Training the Research Team ................................................................... 35

The Core Research Team .......................................................................................................... 35

Team Roles are Varied .............................................................................................................. 36

The Principal Investigator (PI) ................................................................................................... 36


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Co-Principal Investigator ........................................................................................................... 36

Clinical Research Coordinator ................................................................................................... 37

Clinical Research Coordinator Role ........................................................................................... 37

The Data Manager .................................................................................................................... 38

Staff Nurses ............................................................................................................................... 38

Research Team Tips .................................................................................................................. 39

Research Team Networks ......................................................................................................... 39

Training the Research Team ..................................................................................................... 39

Planning a Training Program ..................................................................................................... 40

Goals of Training Program ........................................................................................................ 40

Formal Onsite Training .............................................................................................................. 41

Ongoing, Informal Training ....................................................................................................... 41

Module 4 Quiz ........................................................................................................................... 42

Module 4 Summary ................................................................................................................... 43

Module 5: Handling Site Logistics ................................................................................................. 44

The Sites Logistical Requirements ........................................................................................... 44

Record Keeping & Reporting..................................................................................................... 46

Source Documents .................................................................................................................... 46

Source Document Examples: Medical Reports ......................................................................... 46

Source Document Examples: Progress Notes ........................................................................... 47

Source Document Examples: Screening Log ............................................................................. 47

Source Document Examples: Other Examples ......................................................................... 47

Creating & Preserving Source Documents ................................................................................ 47

Case Report Forms (CRFs) ......................................................................................................... 48


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CRFs and Source Documents .................................................................................................... 48

Regulatory Documents ............................................................................................................. 48

Regulatory Documents ............................................................................................................. 49

Additional Documents & Records ............................................................................................. 49

Avoiding Documentation Pitfalls .............................................................................................. 50

Drug Accountability................................................................................................................... 50

Drug Accountability Tasks ......................................................................................................... 51

Quality Assurance: Good Clinical Practices ............................................................................... 51

Quality Assurance: Standard Operating Procedures ................................................................ 52

QA Helps Meet Requirements .................................................................................................. 52

Final Step: Seeking IRB Approval .............................................................................................. 52

Module 5 Quiz ........................................................................................................................... 53

Module 5 Summary ................................................................................................................... 54

Module 6: Recruiting and Enrolling Participants .......................................................................... 56

Successful Recruitment ............................................................................................................. 56

Collaborating on a Process ........................................................................................................ 56

The Recruitment Process .......................................................................................................... 57

Step 1: Identify the number of participants you will need to recruit ....................................... 57

Step 2: Strategies: Determine you recruitment strategies for the trial ................................... 57

Step 2: Identify barriers to recruitment .................................................................................... 58

Step 3: Screening Participants: Eligibility Criteria ..................................................................... 58

Step 3: Screening Participants: Informed Consent ................................................................... 59

Step 3: Screening Participants: HIPPA ...................................................................................... 61

Step 4: Enrolling Participants: Registration & randomization .................................................. 61


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Step 4: Enrolling Participants: Logistics .................................................................................... 62

Step 5: Document and evaluate your process .......................................................................... 62

Recruiting underrepresented populations: Main Challenges................................................... 63

Recruiting underrepresented populations: NIH Revitalization Act of 1993 ............................. 63

Recruiting underrepresented populations: Recruitment strategies ........................................ 64

Adherence: Retaining participants ........................................................................................... 64

Adherence Tips ......................................................................................................................... 65

Adherence & Follow-up ............................................................................................................ 65

Module 6 Quiz ........................................................................................................................... 65

Module 6 Summary ................................................................................................................... 66

Module 7: Working with Referring Clinicians ............................................................................... 68

The Referring Clinicians Key Task ............................................................................................ 68

A Collaborative Relationship ..................................................................................................... 68

Referring Clinicians Role .......................................................................................................... 68

The Research Teams Role ........................................................................................................ 69

Clinical Trial Education .............................................................................................................. 69

Module 7 Quiz ........................................................................................................................... 71

Module 7 Summary ................................................................................................................... 72

Module 8: Ensuring Study Integrity .............................................................................................. 73

Tasks During the Trial ................................................................................................................ 73

Adverse Event Reporting .......................................................................................................... 73

Compliance with IRB Requirements ......................................................................................... 74

Compliance with IRB Requirements: Continuation or annual review ...................................... 74

Compliance with IRB Requirements: Protocol amendments or revisions ............................... 74


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Compliance with IRB Requirements: Adverse events .............................................................. 75

Ongoing informed consent ....................................................................................................... 75

Quality Assurance ..................................................................................................................... 75

Quality Assurance: Preparing for an audit ................................................................................ 76

Quality Assurance: Internal QA ................................................................................................. 76

Quality Assurance: The audit .................................................................................................... 77

Module 8 Quiz ........................................................................................................................... 77

Module 8 Summary ................................................................................................................... 78


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Module 1: Becoming an Investigator: Considerations

Including Clinical Trials in Your Practice

Welcome to the course Including Clinical Trials in Your Practice: An Overview

With this course, youll be able to explain the value of including NCI-sponsored clinical trials in

your practice. Youll also be able to describe the steps involved.

Well review:

The benefits and responsibilities of conducting NCI-sponsored clinical trials,

Preparing your site for trials, which involves finding a suitable research group as well

as registration and credentialing,

Choosing an appropriate trial for your practice,

Establishing a research team,

Recruiting and enrolling participants, and

Ensuring data integrity.

After every module, youll have the opportunity to test what youve learned by taking a brief

quiz.

Lets begin!

Becoming an Investigator

This module will introduce practical considerations and responsibilities associated with

becoming an investigator.

Upon successful completion of this module, youll be able to:

List the benefits of being a clinical trials investigator,

Identify the benefits and safeguards for participants,

Describe how incorporating clinical trials will affect your practice,

List the responsibilities of a clinical trials investigator, and

Explain how to determine whether clinical trials are a good fit for your practice.


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Investigator Benefits

Becoming a clinical trials investigator offers you the following benefits:

A greater awareness of cutting-edge therapies and the ability to access new

treatments;

A new and/or increased patient base that seeks access to state-of-the-art science

and treatments only available through clinical trials;

Continuing medical education as well as state-of-the art cancer education and

research from the National Cancer Institute;

Increased opportunity to consult with experts in the field, and the chance to be a

source for a second opinion;

Greater access to limited-institution trials;

The potential to achieve additional professional and institutional credentialing aswell as opportunities for a part-time faculty appointment; and,

Ultimately, satisfaction from knowing that you are contributing to the advancementof cancer care.

Patient Benefits

Clinical trials can benefit your patients in the following ways.

Trials within your practice allow patients additional treatment options - beyond

standard care - that may be on the cutting edge.

Through a clinical trial, patients may have access toinvestigational agents,devices,

imaging studies, technology, equipment, or noveldiagnostic techniques at no

additional cost.

Clinical trials have led to significant advancements in breast cancer care. For Example the biologic agent

trastuzumab, or Herceptin, has dramatically improved care for women with breast cancer that harbors

HER2 receptor proteins, which represents about 25% of new breast cancer cases. Women participating

in clinical trials were the first to receive and benefit from treatment with trastuzumab, and participants

in ongoing clinical trials of this agent continue to be the first to benefit in new treatment settings.

According to a 2005 survey, only 9% of newly diagnosed cancer patients were informed about

the possibility of participating in a clinical trial. A majority of those who were offered the

chance agreed to participate in a trial.

Many clinical trial participants have expressed satisfaction and appreciation for the attention

they received during the trial. Also cited as a benefit is the close follow-up that participants

receive after treatment.
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Video Statements:

Diane, a cancer patient, discusses her participation in a clinical trial:

For me, participating in a trial was receiving treatment but with a lot of special

attention. I got a whole lot of extra attention every time, and I felt that I really benefitedfrom that, because there were more people looking at my case than if I had just been in

there in a standard treatment situation.

Ariceli, a cancer patient, discusses her participation in a clinical trial:

They treat you as a human being; and they care for you a lot; and it seems that you are

much more important than their experiment. They give you more attention because

this is experimental. And they try to make sure everythings going well, so they have to

keep a closer eye; they have to monitor my body more, my blood work more.

Patient Safeguards

Clinical trials have associated risks. However, safeguards are built into the process to protect

participants.

Prior to accruing participants, a trial must be approved by anInstitutional Review

Board, or IRB.

The research protocol must ensure consistency in study procedures and minimize

potential risks for participants.

Additional protection measures include strict adherence to the protocol as well as

close monitoring and timely reporting ofadverse events.

Several federal regulations exist to protect participants involved in clinical trials.

Changes to Your Practice

Experienced researchers understand that their practice may grow as a result of clinical trial

participation. One reason is that the practice may be viewed in the community as one that

offers cutting-edge cancer treatment and care options.

At this point, you may be concerned about the administrative burden associated with

conducting clinical trials. Will it be overwhelming? Will your time be compensated?

Dr. James Atkins, an oncologist in Goldsboro, North Carolina, describes how clinical trials have affected

his practice

"Well, since the practice has grown, when I originally came to this town, I was actually

told that this town could not support an oncologist, that it wasn't big enough, and now -

you know we now have four medical oncologists and a radiation oncologist, and the
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radiation oncologist is extremely active in our GOG clinical trials, he's putting as many as

20 to 25 people on RTOG trials a year, so he is extremely active in clinical research in our

group as well, so it has, it has been very good for our practice, for the community.

"I started off with a half time person doing data management, then we got two half time

people, then full time and right now we actually have one full time data manager per

doctor. Because we've put that many people on clinical trials that we need that."

You will need to consider these changes to your practice if you plan to facilitate clinical

research.

First, establish dedicated time for research. As an investigator, you have the

responsibility for supervising each trial, interacting with the IRB, developing budgets,

dealing with audits and inspections, and performing other duties.

Balance your work time between conducting clinical trials and your regular and

customary duties. One estimate is that after youve become familiar with theregulatory, scientific, and fiscal components, you can be quite successful by

allocating 10 to 15% of your time to conducting trials.

Some travel may be required, but will also be a benefit. Investigators may

participate in meetings where protocols are developed and study progress is

reviewed and evaluated. These are also opportunities to network with experts in the

field.

Dr. James Atkins discusses specific impacts to his practice:

"To me, it doesn't take any extra time to treat them on a clinical trial as it does off aclinical trial, so I don't see a time factor in having somebody on a clinical research trial.

The administrative time is primarily going to the IRB meetings and presenting a clinical

trial or answering questions that they may have. But otherwise from an administrative

point of view at the community level, I don't see a lot of extra burden.

"There is some administrative burden for the clinical research professionals, the data

managers - somebody obviously has to work with the protocols and get them through to

the IRB and get them approved and keep up with the paperwork, so there is an

administrative component that other people are also involved with, but for me as a

physician, I don't see a significant administrative burden."

"Your time can be compensated in many, many ways.

"The monies that we are reimbursed technically cover part of data management and

technically there's nothing there to really cover physician time and effort but, my

compensation comes from taking care of my patients, my compensation comes from

the typical clinical oncology that we all do.


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"Word of mouth and the fact the people know that we're involved in clinical research is

an extremely important issue in maintaining your referral base."

Why become an investigator

Health professionals become investigators for many reasons. Ultimately, they want to help

advance science and provide better cancer prevention and treatment to the public.

When determining whether you should participate, it may be helpful to hear from colleagues

who have been there.

Dr. Atkins discuss why he became an investigator, and recommendations for new investigators

"After I got out into practice, I decided that it was very important to be involved in the

clinical trial system. I knew that the most exciting advances that were going to occur in

oncology were probably going to occur in the next 20 years. Here we are 18 years later,and I was right - we are at a very exciting time in oncology, and so I wanted to be in the

action. I wanted to be involved in the clinical research and what was going on

nationwide; I didn't want to get left behind.

"Being a part of the clinical trial system, I'm involved with new protocols, new concepts,

new ways of looking at things, from the very beginning. I think there's a lot going on

right now in the grassroots efforts to educate patients. We're going to see more and

more patients requesting clinical trials and the doctors who are not in the system are

going to lose market share."

"If a new researcher wanted to...a new person wanted to get involved, then you can say

okay, I'm only going to open two clinical trials. They can say I'm only going to open up

two. I'm going to open one up for colon cancer; I'm going to open one for breast

cancer. And I will put every single one of my new colon cancers on that clinical trial, and

I will put every single one of my new breast cancers on that breast cancer trial. And just

by doing that, I would expect that most clinical oncologists should be able to put 10

people anyway, if not more, on clinical trials a year.

"The bottom line is you need doctors who are interested in doing the clinical trials, who

want to answer the questions, who want to be a part of the system, because it costs

money to get the system - a community up and running. It will cost probably $5,000 -$10,000 and so you don't want to put $5,000 - $10,000 into developing a community

and then have them not put anybody on.

"One of the things that I would recommend is that they have their own data manager.

It doesn't mean the person has to be full-time. They can be half time. I think that one

of the errors that people make is not taking the commitment.


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"It has to be a philosophical commitment too. They need to make the commitment that

clinical trials represent the cutting edge of medicine. I'll look at the clinical trials as the

very best...that the best cancer minds in our country have put together.

"I think that they need to be willing to say I don't know which treatment is best and

therefore I am going to do this clinical trial, and they have to believe that. They may

have biases, okay, and I had biases. And we have to acknowledge what our biases are

when we do clinical research."

Dr. Gorsch discusseswhy he offers patients clinical trials, and his recommendations for

reducing the administrative burden:

There have been some classic examples in oncology where we have done the wrong

thing because we didnt have the data and people were reluctant to get the data. Foryears in the treatment of lymphoma, it looked like newer regimens were better than the

older regimens. And it made sense intuitively. When the studies looking at a comparison

directly between the newer and the older regimen were finally done, we found that the

older regimen was just as good and less toxic than the newer regimens. So if were going

to do our patients a service, we need to know that what we do works. And the only way

we really know is by participating in clinical trials. And I love being able to offer patients

clinical trials and say to them, Look, this is, to our knowledge, the state of the artthe

best that we have. Only by doing these studies are we really going to know what is

really the best treatment. Thats the principal reason we decided to participate.

"The single best thing they could do is to hire a good data manager. If you have a good

data manager, she can support you and do the lion's share of the paperwork in terms of

scheduling the appropriate tests, filling out the right forms, checking the eligibility on

patients.

"Being a participant through a major university as a sponsor is helpful because then you

have their resources as well as a backup. It's not very difficult to do. When you come

right down to it, having - offering clinical studies, clinical trials is really not difficult,

provided that you have someone helping you with the paperwork."

Investigator Responsibilities

Serving as a clinical trials investigator is rewarding in many ways, but it also requires

commitment and research expertise. The investigator is ultimately responsible for overseeing

the conduct of the study at his or her site. These responsibilities may include:

Protocol management,


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Maintenance of an adequate rate of patient accrual to studies,

Supervision and training of research team members,

Compliance with federal, state, and institutional regulations,

Assurance that the highest standards of ethics and quality are met, Provision of informed consent to patients and compliance with all human

participants protection regulations,

Management of investigational agents,

Assurance that there is no financial conflict of interest, and

Participation in the auditing and quality assurance process.

For more details on investigator duties, please visit theCTEP Investigators HandbookonCancer.gov.

What you can offer

There are many ways to become an investigator. While exploring options, its important to

choose a good fit; that is, one or more trials that will best serve your practice, your patients,

and your community.

Consider your practice. Is it prepared to incorporate clinical trials? You must dedicate time and

staff resources to research, as well as be personally committed. Do you envision running a few

studies versus a large amount? For new investigators, its often better to conduct one cancer

study well than attempt 10 at once and run them poorly.

Also consider your patients. Is your patient population receptive to participating in a trial? Do you have

patients whom you know would benefit from a trial?

And finally, consider the impact to your community. Providing clinical trials increases the communitys

options for treatment, bringing state-of-the-art science to where patients live. But, you must consider to

what extent your community is willing to support the trials you plan to introduce. And, youll need to

take time to educate your patients and community.

Next, lets test your knowledge with a short quiz on what youve learned in Module 1.

Module 1 Quiz

Question 1: Which statement about the benefits of clinical trials is incorrect?

a) Clinical trial investigators can provide their patients with opportunities for new

treatments, even in rural clinics

b) Patients will have to split their clinic time between the clinical trial they participate

in, and their regular course of treatment
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c)

d)

Costs may be reduced for patients in clinical trials for services such as

investigational agents and imaging studies

Correct Answer: b

Patients who participate in clinical trials do so in lieu of their regular course of treatment

Question 2: Establishing clinical trials research within your practice could affect it in what way?

Safeguards for patients include IRB review and adverse event reporting

a)

b)

Reducing the time you spend on your regular practice by at least half

c)

Necessitating hiring a large staff

d)

More opportunities to network with other investigators to review protocols, review

and evaluate studies, and network with experts in the field, which could also take

time away from your practice

Correct Answer: c

Clinical trials provide you with the opportunity to network outside your practice with

other investigators and experts in the field, which will also take time away from your

practice

Question 3: Serving as a clinical trials investigator is rewarding in many ways, but it also

requires commitment and research expertise. Responsibilities of an investigator include all of

the following EXCEPT:

Diminished ability to hire staff to facilitate your existing practice

a)

b)

Supervising research team members

c)

Participating in the auditing/quality assurance process

d)Collecting data from each patient, on every visit

e)

Implementing informed consent

Correct Answer: c

Responsibilities include supervising team members, participating in the auditing

process, implementing informed consent, and maintaining accrual. However, if you

build the proper team, your staff should perform the data collection tasks.

Question 4: When determining whether offering clinical trials would be good for your practice,consider:

Maintaining an adequate rate of patient accrual

a)

b)

Trials that would benefit your practice, your patients, and your community

c)Trials that would benefit your practice, providing a steady stream of income

d)Only those trials that would benefit at least 40% of your patient population

Trials that have the potential to draw significant attention to your community


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Correct Answer: a

When considering offering clinical trials, consider those that would benefit your

practice, your patients, and your community

Module 1 Summary

Congratulations! Youve now completed Module 1: Becoming an Investigator: Considerations.

You have learned about:

The benefits of being a clinical trials investigator,

The benefits and safeguards for participants,

How incorporating clinical trials will affect your practice,

Responsibilities of a clinical trials investigator, and

Considerations for determining whether clinical trials are a good fit for your practice

In the next module, well discuss the groups you can join in order to access clinical trials, as well

as required credentialing.


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Module 2: Initial Site Preparation

In this module, well explore how to find clinical trials and the organizations that support them,

for both NCI-supported and industry-supported trials. Well focus on NCI-supported trials while

we review membership and credentialing requirements, including how to find an InstitutionalReview Board, or IRB, of record.


List the organizations through which investigators conduct clinical trials,

Summarize the methods to identify anIRBof record, and

Describe different registration and credentialing requirements.

Initial Considerations

Lets begin by exploring how to find the types of trials that would suit you and your practice.

First, start networking by identifying existing institutional memberships and partnerships

available to you and your practice. Also, talk to other investigators in the field.

Here are some questions to get you started:

Does your local hospital have a research department or already participate in other

clinical trials?

Do you have access to a research program through a university in your region or

through professional affiliations?

Do any of your colleagues participate in cancer clinical trials? If so, what networks do

they participate in?

What type of membership affiliations are available through your professional

organizations?

Next, identify the types of studies you want to participate in, such as:

Government-sponsored or industry-sponsored trials,

Investigator-initiated trials, or trials that you write and develop, Disease-specific trials,

Phase I, II, or III trials, and

Screening, treatment, prevention,quality-of-life, and symptom management trials.

A typical trial may include one or more of these types (for example, aPhase IIIbreast cancer

trial).
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Also, each type of study has specific membership and credentialing requirements. Well discuss

these later in this module.

Ways to Participate in Trials

There are several ways to become a clinical trials investigator. You and/or your institution maybe able to participate through:

One of NCIs Clinical Trials Cooperative Groups through an academic center or

community hospital,

NCIs Community Clinical Oncology Program, or CCOP,

NCIs Cancer Trials Support Unit, or CTSU,

Participation as a site or satellite site in NCIs Cancer Centers Program, and finally,

Clinical trials sponsored by pharmaceutical and biotech companies.

Lets review each option in more detail.

NCIs Clinical Trials Cooperative Groups

NCIs Clinical Trials Cooperative Group Program is designed to promote and support clinical

trials of new cancer treatments, to explore methods of cancer prevention and early detection,

and to study quality-of-life issues andrehabilitationduring and after treatment. This program

includes translational research and lab science.

Cooperative groups are composed of academic institutions and cancer treatment centers as

well as NCIs CCOP. They differ in structure and research focus. Some groups concentrate ontreatment of a single type of cancer; some study a specific type of cancer therapy; others have

a broader focus.

To get involved, first contact the membership department of a group that interests you. Health

professionals in the community can join cooperative groups through the sponsorship of one of

the main group members, such as a university medical center. For instance, you can contact

your training institution and request the sponsorship, provided that it is a main member of a

cooperative group. Note that investigators can participate in one or more groups

simultaneously.

For more information: See theFactsheet for NCIs Clinical Trials Cooperative Groups programonCancer.gov.

NCIs Community Clinical Oncology Program (CCOP)

NCIs CCOP helps transfer the latest research findings to the community level, so patients dont

have to leave their community to receive state-of-the-art care. It also increases the number of
http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=441257http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=441257http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=441257http://www.cancer.gov/cancertopics/factsheet/NCI/clinical-trials-cooperative-grouphttp://www.cancer.gov/cancertopics/factsheet/NCI/clinical-trials-cooperative-grouphttp://www.cancer.gov/cancertopics/factsheet/NCI/clinical-trials-cooperative-grouphttp://www.cancer.gov/cancertopics/factsheet/NCI/clinical-trials-cooperative-grouphttp://www.cancer.gov/Templates/db_alpha.aspx?CdrID=441257


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participants and physicians who can take part in clinical trials operated simultaneously in major

research centers and in the community.

CCOPs are composed of community physicians who work with scientists conducting NCI-

supported clinical trials.

To get involved, contact CCOP programs directly.

For more information: visit theCommunity Clinical Oncology Program (CCOP) Web siteforprocedures, forms , and applications

NCIs Cancer Trials Support Unit (CTSU)

NCIs Cancer Trials Support Unit, or CTSU, is designed to increase accrual to larger Phase III

adult oncology trials for physicians that currently do not have access to these trials. The

program provides sites with the freedom to choose trials that best suit their patient population

and scientific interests without more restrictive requirements. It also provides standardizedtools and support for conducting trials.

Health professionals, whether affiliated with a Cooperative Group or not, are eligible to register

with the CTSU to access these standardized tools.

For more information: Visit the NCIs Cancer Trials Support Unit (CTSU) Web sitefor moreinformation and registration.

NCIs Cancer Centers Program

NCIs Cancer Centers Program sustains broad-based, coordinated, interdisciplinary programs incancer research.

The program supports major academic and research institutions throughout the United States

that have a strong commitment to laboratory, clinical, and population-based cancer research as

well as scientifically strongresearch bases.

To get involved, first determine which regional cancer centers you have access to, and then

determine if their specialties match your interests. Then contact the individual center.

For more information: Visit the Cancer Centers Program home pagefor a list of NCI sponsored

cancer centers as well as policies and guidelines.

Private Industry-sponsored Trials

Pharmaceutical and biotech companies are active in new drug development in four ways:

Initially exploring new agents for clinical activity with the NCIs Cancer Therapy

Evaluation Program, or CTEP,
http://dcp.cancer.gov/programs-resources/programs/ccophttp://dcp.cancer.gov/programs-resources/programs/ccophttp://dcp.cancer.gov/programs-resources/programs/ccophttps://www.ctsu.org/https://www.ctsu.org/https://www.ctsu.org/https://www.ctsu.org/http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635297http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635297http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635297http://cancercenters.cancer.gov/http://cancercenters.cancer.gov/http://cancercenters.cancer.gov/http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635297https://www.ctsu.org/http://dcp.cancer.gov/programs-resources/programs/ccop


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Collaboration with NCI Cooperative Groups,

Industry-designed studies with a selected research base of one or more institutions,

and

Support of institutional trials.

Pharmaceutical companies are now the major developers of cancer drugs. Most of their studies

are done independently of NCI.

To find these trials:

Attend your own specialty meetings,

Attend industry meetings and conferences,

Contact aContract Research Organization, or CRO - an independent contractor thatassumes one or more of the obligations of a sponsor during a clinical trial, and

Interface with medical science liaisons associated with the pharmaceutical industryand who work in specific diseases of interest to you.

For more information:

Visit the website forPharmaceutical Research and Manufacturers of America

VisitClinicaltrials.govfor contacts for all clinical trials

Visit theFDA Web sitefor information onFDAsponsored clinical trials.

Identifying an IRB of Record

The next step in setting up clinical trials is identifying an IRB of record.

In the United States, all clinical trials are conducted under the close supervision of an IRB that

has jurisdiction over the trials. Such an IRB becomes a clinical trials IRB of record.

An IRB protects the rights, safety, and welfare of human research participants and is required to

comply with federal regulations.

As an investigator, you should explore options for IRBs available to your site and clarify

authority and governance within your practice and care network(s).

The following resources might assist you in identifying an IRB of record and other regulatory

resources: risk and compliance departments at your affiliated institutions, sponsoring research

organizations, andquality assurancedepartments within your sites research networks.
http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635303http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635303http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635303http://www.phrma.org/http://www.phrma.org/http://clinicaltrials.gov/http://clinicaltrials.gov/http://clinicaltrials.gov/http://clinicaltrials.gov/http://www.fda.gov/oc/gcp/default.htmhttp://www.fda.gov/oc/gcp/default.htmhttp://www.fda.gov/oc/gcp/default.htmhttp://www.cancer.gov/Templates/db_alpha.aspx?CdrID=454786http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=454786http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=454786http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635399http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635399http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635399http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635399http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=454786http://www.fda.gov/oc/gcp/default.htmhttp://clinicaltrials.gov/http://www.phrma.org/http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635303


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Identifying an IRB of Record

When choosing an IRB of record, consider the IRBs experience, history of successful audits,

accreditation, accessibility, and user-friendliness for your site.

Options for IRB affiliation might include:

Local or regional academic medical centers,

Local or regional hospitals,

Developing a site-specific IRB (although not encouraged for a site newly entering the

research field),

National IRBs, such as the NCI Central IRB, and

Commercial IRBs, such as the Western IRB.

The principal investigator must obtain a copy of the IRBs policies and procedures to ensurethat expectations and processes are clear.

The NCI CIRB

The NCI Central IRB, or NCI CIRB, reviews Cooperative Group trials to enable local IRBs to

rapidly approve these trials. Through a facilitated review process, patients and their physicians

benefit from improved access.

The NCI CIRB also provides consistent, expert IRB review at the national level before the

protocol is distributed to local investigators, which enhances the protection of research

participants.

And finally, the NCI CIRB reduces the administrative burdens on local IRBs and investigators

associated with IRB submission.

The NCI CIRB Process

The NCI CIRB doesnt replace the local IRB; instead, it partners with local IRBs by performing

full-board review of Cooperative Group clinical trials. These trials can then be accepted by local

IRBs, who must ensure that the local context requirements are met.

The NCI CIRB Process

Lets review the NCI CIRB process:

First, the NCI CIRB reviews and approves theprotocols(and associated materials) for Cooperative Group

studies.

Next, it notifies the local investigator when a new study is approved through a routine group activation

announcement or through the NCI CIRB biweekly Study Activity Update e-mail.
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Then, the local investigator decides to open the study. Research or IRB staff downloads the completed

application and study documents from the NCI CIRB Web site and submit documents to the local IRB.

Next, the local IRB chair or subcommittee assesses the NCI CIRB review and decides whether or not to

accept it. If it is accepted:

The NCI CIRB becomes the IRB of record for thatstudy at thatsite,

The NCI CIRB is responsible for full-board review of amendments, annual continuing

reviews, adverse events, etc., and

The local IRB is responsible for conducting the study within its institution, including

review of adverse events occurring at their site.

More information about this process is available on the NCI CIRB Web site

Registering with the FDA: The 1572 Form

If your trial uses investigative agents, the next step in the process is to register with the FDA asan investigator.

Before a site is permitted to conduct a trial for a new drug or device, the principal investigator

must complete the Statement of Investigator Form (referred to as a 1572 form) that the

sponsor files with the FDA.

The1572 formprovides the FDA with the following information:

The site name,

The site address, The CV of the principal investigator,

Information regarding sub-investigators, research sites, and clinical laboratories, and

The IRB of record for your site.

These regulations are FDA-specific. Investigators may also need to comply with theOffice for

Human Research Protections, or OHRP [oh-HARP], and the Department of Health and Human

Services, or DHHS, regulations. Check with the trial sponsor on which regulations to follow.

Visit the FDA web site for a copy of the 1572 formand instructions for completions and submission

1572 Form Commitments

The 1572 form is a legal contract between you and the FDA, ensuring that you will comply with

all requirements outlined in the Code of Federal Regulations and other guidelines governing

research involving human subjects.
http://www.ncicirb.org/CIRB_FAQ.asphttp://www.ncicirb.org/CIRB_FAQ.asphttp://www.ncicirb.org/CIRB_FAQ.asphttp://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635418http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635418http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635418http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635474http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635474http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635474http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635474http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM074728.pdfhttp://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM074728.pdfhttp://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM074728.pdfhttp://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM074728.pdfhttp://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635474http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635474http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635474http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635418http://www.ncicirb.org/CIRB_FAQ.asp


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On the back of the 1572 form is a set of commitments. By signing the form, you agree to abide

by these commitments. These are very important; you can be fined and jailed if you do not

comply with them!

Commitment 1

I agree to conduct the study(ies) in accordance with the relevant, current protocol(s)

and will only make changes in a protocol after notifying the sponsor, except when

necessary to protect the safety, rights, or welfare of subjects.

Commitment 2

I agree to personally conduct or supervise the described investigation(s).

Commitment 3

I agree to inform any patients, or any persons used as controls, that the drugs are being

used for investigational purposes and I will ensure that the requirements relation to

obtaining informed consent in CFR Part 50 and institutional review board (IRB) reviewand approval in 21 CFR Part 56 are met.

Commitment 4

I agree to report to the sponsor adverse experiences that occur in the course of the

investigation(s) in accordance with 21 CFR 312.64.

Commitment 5

I have read and understand the information in the investigator's brochure, including the

potential risks and side effects of the drug.

Commitment 6

I agree to ensure that all associates, colleagues, and employees assisting in the conduct

of the study(ies) are informed about their obligations in meeting the above

commitments.

Commitment 7

I agree to maintain adequate and accurate records in accordance with 21 CFR 312.62

and to make those records available for inspection in accordance with 21 CFR 312.68.

Commitment 8

I will ensure that an IRB that complies with the requirements of 21 CFR Part 56 will beresponsible for the initial and continuing review and approval of the clinical

investigation. I also agree to promptly report to the IRB all changes in the research

activity and all unanticipated problems involving risks to human subjects or others.

Additionally, I will not make changes in the research without IRB approval, except where

necessary to eliminate apparent immediate hazards to human subjects.


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Commitment 9

I agree to comply with all other requirements regarding the obligations of clinical

investigators and all other pertinent requirements in 21 CFR Part 312.

Additional Requirements

In addition to registering with the FDA, you should verify any additional requirements with your

sites sponsors and oversight authorities (for example, your sites IRB).

Three additional required documents include:

The site roster

o Your site must submit roster forms and other data to the sponsor to ensure ongoing

communication. Once an investigator, team, and site are registered, then other NCI

research sponsors will be able to access this data.

o After your site has submitted the data, review the database listing to ensure

accuracy and prevent gaps in site identification.

Proof of human subjects protection training, and

o All investigators and members of the research team need to complete education in

the protection of human research subjects.

o Verify the required training programs with the sponsor and any regulatory

authorities, such as the FDA and OHRP [oh-HARP].

o TheNIH online tutorialis generally accepted by most research sponsors. Be sure to

print and save a copy of the certificate for completion.

The Federal wide Assurance, or FWA.

o The FWA is a written, binding commitment filed by the research site or responsible

institution with the Federal Government that promises compliance with applicable

regulations governing human subject research. Usually the IRB files the FWA; in

other cases, the investigator will file.

o The FWA ensures that activities related to human subject research that government

agencies fund or sponsor, will be:

Guided by the ethical principles found in theBelmont Report

Comply withHHS regulations for human research protections

Satisfy theFDA regulationsrelating to Good Clinical Practices, or GCPs, and

clinical trials as well asHIPAA regulations.
http://phrp.nihtraining.com/http://phrp.nihtraining.com/http://phrp.nihtraining.com/http://ohsr.od.nih.gov/guidelines/belmont.htmlhttp://ohsr.od.nih.gov/guidelines/belmont.htmlhttp://ohsr.od.nih.gov/guidelines/belmont.htmlhttp://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htmhttp://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htmhttp://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htmhttp://www.fda.gov/oc/gcp/regulations.htmlhttp://www.fda.gov/oc/gcp/regulations.htmlhttp://www.fda.gov/oc/gcp/regulations.htmlhttp://www.hhs.gov/ocr/hipaa/http://www.hhs.gov/ocr/hipaa/http://www.hhs.gov/ocr/hipaa/http://www.hhs.gov/ocr/hipaa/http://www.fda.gov/oc/gcp/regulations.htmlhttp://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htmhttp://ohsr.od.nih.gov/guidelines/belmont.htmlhttp://phrp.nihtraining.com/


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This section concludes Module 2. Next there is a short quiz to review what youve learned.

Quiz

Question 1: Select whether the following statement is True or False:

NCIs CTSU program allows investigators to join larger Phase III trials whether or not they are

affiliated with a Cooperative Group.

a)

b)

True

Correct Answer: a

Thats correct! NCIs CTSU program allows investigators to join larger Phase III trials

whether or not they are affiliated with a Cooperative Group.

Question 2: The NCI CIRB:

False

a)

b)Provides a regulatory option for Phase I NCI clinical trials

b. Replaces the IRB of record for the investigator

c)s practice

d)Reduces the administrative burden on the IRB of record

Correct Answer: c

Thats correct! The NCI CIRB reduces the administrative burden on the IRB of record, but

does not replace it.

Question 3: Registration and Credentialing requirements for NIH investigators include the FDAs

1572 form, a site roster, the FWA commitment, and

Allows the IRB of record to assume responsibility for full-board reviews of clinical

trials

a)

b)NCI CIRB approval letter

c)Completed human subjects protection training for all research team members

d)A detailed budget

Correct Answer: b

Thats correct! Registration and credentialing requirements for NIH investigators includeproof of completion of human subjects protection training for all research team

members.

None; the 1572 form, a site roster, and the FWA commitment are all of the

requirements


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Module 2 Summary

Congratulations! You have now completed Module 2: Initial Site Preparation. You have learned

about

The organizations through which investigators conduct clinical trials,

Ways to identify an IRB of record, and

Different registration and credentialing requirements.

In the next module, well review how to choose the best trial for your practice.


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Module 3: Choosing the Trial(s)

In this module, well discuss various aspects of specific clinical trials that will help you

determine which would be best for your practice.


List several factors to consider when choosing clinical trials,

Describe several processes involved in evaluating trials, and

Identify potential sources of funding and reimbursement

Choosing a Specific Trial

When building a trial menu (also referred to as a portfolio), carefully consider choosing trials

to which you can successfully accrue participants. Keep in mind that some trials may neveraccrue more than a few participants, but you may choose to open those trials for the

participant who presents with a rare cancer.

Factors to Consider

Factors to consider when choosing the right trials include:

Scientific value to you: Are you interested in the science behind the study?

Availability of the patient population, not just in your practice, but with colleagues

you are affiliated with.

The local community supporting the trial, which needs to feel that the trial is the

appropriate care.

The trials feasibility within your clinical care and resource networks: Do you have

the resources, such as the supplies, the drugs, and the equipment to support the

trial?

The time required to initiate and maintain the credentialing and regulatory

components, which continue throughout the trial.

Your ability to support the sponsors expectations: Make sure you know how the

sponsor will manage your site, to avoid hidden or unexpected costs, such as their

monitoring or auditing requirements.

Any other competing trials: Avoid similar trials that compete for the same

population.

The trials affordability: Understand your financial limits, for example, whether your

site needs to make money, is able to take a loss, or can just break even.


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Here are a few examples of ways to build a good accrual network.

If you have a strong affiliation with surgeons at a hospital, become familiar with the

types of cancer they address,

Urologistsare a good source of prostate cancer patients and can direct you toeligible patients,

Affiliate withgastroenterologists, who are performing colonoscopies, and

If you are interested in lung cancer, affiliate with apulmonary specialist.

Also, there may be a business opportunity for your colleagues to refer patients to your clinical

trials.

Processes to Assist Trial Selection

The principal investigator will choose the trials for his or her site. Various tools and processescan help determine trials that are a good fit. These may include:

Feasibility checklists, to guide a practical logistical review before opening a trial;

Accrual tracking worksheets, which help your site monitor accrual and analyze your

patient population;

Investigator committee meetings and tumor boards provide an opportunity to

discuss feasibility of a particular trial with colleagues;

Research team feasibility reviews provide an opportunity for the future research

team to meet and review ALL aspects of the trial in depth - for example, equipment,

systems, people, and money; and

Engaging affected departments, for example, pharmacy, lab, pathology, nuclear

medicine staff, radiation oncology, physicists, and others, and ensuring that they are

willing to participate in a trial.

Here is a sample feasibility issue and questions:

A researcher met with a melanoma committee composed of physicians and researchers to

discuss potential melanoma trials. Before the researcher put all resources into participating in a

melanoma trial, he evaluated the number of past and ongoing patients.

Evaluating trials will require considerable scrutiny of the specific trials requirements. Here are

examples from selected studies:

Does your pharmacy have the right security and staff, in case the trial requires a

drug or reaction tracked and recorded differently from your normal procedures, for

example, adouble-blind?
http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=46643http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=46643http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=46387http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=46387http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=46387http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=538155http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=538155http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=538155http://www.cancer.gov/dictionary/?CdrID=45673http://www.cancer.gov/dictionary/?CdrID=45673http://www.cancer.gov/dictionary/?CdrID=45673http://www.cancer.gov/dictionary/?CdrID=45673http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=538155http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=46387http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=46643


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Do you have access to a nuclear pharmacy? Does your budget allow for an expensive

injection?

Does the study require imaging technology? Do you have the right machines? Canthe trials participants have access to them when they are available?

Established Forms and Procedures

Another factor in evaluating trials is whether the trial already has established forms and

procedures in place. Standard forms and procedures are required for both the site and the trial

- study sponsors may require that they be in place before approving a site for participation. If

the study sponsor does not provide these, youll need to develop them.

It may be easier for new investigators to choose trials that already have forms and procedures

developed. Research documentation requirements are often very specific and may require

information not routinely included in standard notes and reports.

Forms and procedures must be specific for the site and accurately and succinctly reflect actual

practice. Its considered a best practice that every site invest time in developing written

policies and procedures, specific to the individual site, that define all aspects of study conduct.

Consistency is a critical element of research practice.

Standard Operating Procedure, or SOP guidelines, workshops, and templates can be found

through professional societies or commercial vendors.

Standard of caredocumentation may not fully meet the needs of clinical trials - your site will

still have to develop additional tools and forms.

Well review documentation in more depth in Module 5.

Funding and Reimbursement

Funding your research efforts is not an easy task. Funding and reimbursement may be

composed of actual resources such asinvestigational agents,devices,imaging studies, or novel

diagnostic techniques. Potential sources of funding and reimbursement include sponsors,

insurance, Medicare, or local institutions.

We recommend that your site conduct a thorough assessment of the trial requirements and

actual costs prior to opening a study, to ensure that you have the resources to maintain apatient population throughout the trial as well as develop a strong research program.

Success is determined by your sites program goals and what you want to accomplish. Some

sites may lose money up front, and some realize a profit immediately. For example, a hospital

might go into the red in order to build a research practice.
http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635306http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635306http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=346525http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=346525http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=446561http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=446561http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=446561http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635288http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635288http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635288http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=46361http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=46361http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=46361http://www.cancer.gov/dictionary/?CdrID=635290http://www.cancer.gov/dictionary/?CdrID=635290http://www.cancer.gov/dictionary/?CdrID=635290http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=46361http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635288http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=446561http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=346525http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=635306


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Startup and Ongoing Expenses

Participation in clinical trials requires startup capital. Investigators who have set up their regular

practice will still need to put the staff and infrastructure in place to run clinical trials. Potential

costs for community physicians include:

Personnel, with roles such as a research nurse, a clinical research coordinator, a

secretary, and pharmacist services, that may grow over time;

Office expenses, such as workspace, computer access, phone, fax, and mail;

Physician time, such as reviewing potential studies,IRBrequirements, patientdiscussions, and monitoring and ensuring protocol compliance;

Meeting time, with research staff, referring physicians, and possibly travel; and

Other expenses, such as assessing insurance issues, IRB fees, audits, chart storage

fees, and protocol requirements that the sponsor doesnt cover.

Experienced community investigators recommend that you hire a dedicated nurse or

coordinator to keep your sites study coordination and data management at peak performance.

These team members play a key role in the success of implementing trials in your practice.

Well review these roles in more detail in Module 4.

Sponsor Reimbursement

Sponsors, such as NCI or private industry, may reimburse sites to cover the research costs of

clinical trials. Amounts can vary. For example, if a research site participates in an NCI or private

industry-sponsored clinical trial, the sponsor may pay a defined amount per participant

registration.

The sponsors determine the amount of startup funds and when they are available to your site.

For example, one sponsor may pay a percentage of the total budget as an upfront payment,

while another may not pay anything until the first participant is enrolled.

Clarify your sites funding availability and negotiate your sites needs before opening a trial.

In many community investigators experiences, the financial reimbursement from sponsors may

be used to pay research team expenses. Sponsors also may be able to identify additional

sources for support if the investigator encounters funding problems.

Insurance Reimbursement

To understand how insurance companies reimburse expenses associated with a trial, lets

consider how insurance companies categorize them.
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First, there are patient care costs. Usual care costs include items such as doctor visits, hospital

stays, clinical laboratory tests, and x-rays, which occur whether the patient is participating in a

trial or receiving standard treatment. These costs have usually been covered by a third-party

health plan, such as Medicare or private insurance.

Extra care costs are associated with clinical trial participation, such as additional tests required

to evaluate the study interventions. These may or may not be fully covered by the clinical trial

sponsor or research institution. In some cases, the sponsor and the participants health plan

should resolve coverage.

Second, there are research costs associated with conducting the trial, such as data collection

and management, research physician and nurse time, and data analysis. Such costs are usually

covered by the sponsoring organization, such as NCI or a pharmaceutical company.

Some insurance will not cover any clinical trials. Many states have laws related to coverage for

government-funded research. VisitNCIs Web sitefor information on states insurance coverage ofclinical trials.

Health insurance companies and managed care companies decide which health care services they may

pay for by developing a coverage policy regarding the specific services.

In general, the most important factor determining coverage is a health plans judgment as to whether

the service is established or investigational.

Health plans usually designate a service as established if there is a certain amount of scientific data to

show that its safe and effective. If the health plan doesnt think that such data exist in sufficient

quantity, the plan may label the service as investigational.

For some health plans, clinical trial participation may result in a denial of coverage. However,

some health insurance plans make case-by-case decisions about clinical trials, and some health

insurers, such as Medicare, now cover the usual patient-care costs.

A health plan may also define specific criteria that a trial must meet before extending coverage,

such as:

Lack ofstandard therapy: Some plans may limit coverage of trials to situations

where no standard therapy is available.

Sponsorship: Some plans may only cover costs of trials sponsored by organizationswhose review and oversight of the trial they consider to be careful and scientifically

rigorous.

Medical necessity, trial type, and trial phase: Some plans may cover patient care

costs only for the clinical trials they judge to be medically necessary on a case-by-

case basis
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The type of trial may also affect coverage: it may be more difficult to get coverage

for the care costs associated with prevention and screening trials.

Additionally, while a plan may be willing to cover costs associated with Phase III

trials, which include treatments that have already been successful with a certain

number of people, the plan may require some documentation of effectivenessbefore covering a Phase I or II trial.

Cost neutrality: Some health plans may limit coverage to trials they consider cost-

neutral - that is, not significantly more expensive than treatments considered

standard.

Facility and personnel qualifications: A health plan may require that the facility and

medical staff meet specific qualifications to conduct a trial involving unique services,

especially intensive therapy such as a bone marrow transplant (for example, high-

dose chemotherapy with bone marrow/stem cell rescue): A health plan may require

that the facility and medical staff meet specific qualifications to conduct a trial

involving unique services, especially intensive therapy such as abone marrow

transplant(for example, high-dose chemotherapy with bone marrow/stem cell

rescue).

Some health plans, especially smaller ones, will not cover any costs associated with a clinical

trial. Policies vary widely, but in most cases the investigator should consider initiating

discussions with the health plan, before the participant is enrolled in the trial. You may have to

advocate for the participant and obtain preapproval, if necessary.

Medicare Coverage

In general, Medicare covers cancer treatment and diagnosis trials if:

They are funded by NCI, NCI-designated Cancer Centers, NCI-Sponsored Clinical

Trials Cooperative Groups, and other federal agencies that fund cancer research.

Other trials may be eligible for coverage and the investigator can ask Medicare to

pay the participants costs.

The purpose or subject of the trial is within a Medicare benefit category. For

example, cancer diagnosis and treatment are Medicare benefits, so these trials are

typically covered.

View theNCI fact sheetfor Medicare beneficiaries and visit theCenters for Medicareand Medicaid Services.

Costs not covered by Medicare include:

Investigational items or services being tested in a trial; in this situation, sponsors of

clinical trials often provide the new drug for free,

Items or services used solely for the data collection needs of the trial,
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Anything that the sponsor provides for free, and

Cancer prevention trials.

For a participant, Medicare may pay the following:

Anything normally covered is still covered when its part of a clinical trial, even if itsa service or item associated with the trials treatment. This includes tests,

procedures, and doctor visits that are ordinarily covered.

For example, while the sponsor pays for the new chemotherapy drug being tested in

a trial, Medicare may pay for the intravenous administration of the drug, including

any therapy to prevent side effects.

Anything normally covered even if it resulted from participation in the clinical trial.

For example, Medicare may pay for a test or hospitalization resulting from a side

effect of the new treatment that it would ordinarily cover.

Local Institution Support

To supplement external funding sources, your local institution or practice may need to provide

additional support, especially in the start-up phase of your program. This support may include

office space, staff support, computers, supplies, IRB services, human resources, benefits

management and even financial support.

Work with senior level management at your local institution, so they understand the value of

your research program and what it brings to your community. Your institution can gain prestige

by sponsoring a clinical trials research program and providing state-of-the-art cancer care.

Module 3 Quiz

Question 1: Which statement is INCORRECT regarding factors to consider when choosing clinical

trials?

a)

b)

A trial that already has established forms and procedures will be easier for a new

investigator to select

c)

The patient population you have to choose from, must derive from your own

practice

d)

A new investigator should perform some research to determine whether there are

any competing trials similar to the one he/she is considering

Correct Answer: b

Thats correct! Patient populations can derive from your own practice or from

colleagues and affiliations.

A new investigator should consider the time required to maintain certain

components of a trial


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Question 2: Potential processes and tools to help you determine the best trials for your site

include:

a)

b)Feasibility reviews with your practice

c)

Meeting with any affected departments in your practice, such as pharmacy

d)

Meeting with colleagues

e)

Checklists and worksheets found online

Correct Answer: e

Thats correct! Potential processes include feasibility reviews with your research team as

well as affected departments, meetings with colleagues, and checklists and tools that

you can find online.

Question 3: Select whether this statement is True or False:

Sponsors will cover all costs related to research team expenses for each trial; additional expensesmay vary.

All of the above

a) True

b) False

Correct Answer: b

Thats correct! Sponsors will not necessarily cover all expenses for a sites participation

in a clinical trial. Investigators should verify with sponsors as to what they will

reimburse.

Question 4: Which statement concerning insurance reimbursement is correct?

a)

b)

Health insurance companies cannot restrict potential reimbursement on the basis

of the sponsor or facility qualifications

The investigator will not need to contact the patients

c)

insurance companies; that is

the responsibility of the individual patient or the sponsor

d)

Most health insurance coverage of clinical trial participation is conditional: some

may deny coverage, some make case-by-case decisions, and some may cover costs

for treatment that is not significantly different than standard care

Correct Answer: c

Most insurance companies will consider cancer prevention trials

Thats correct! Health insurance coverage of trials is conditional. Coverage will dependon the individual insurance company or organization.

Question 5: For a participant, Medicare will pay for:

a) Items that the sponsor will not provide


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b)

c)Anything normally covered

d)

Prevention trials

Correct Answer: b

Thats correct! Medicare will cover anything normally covered by insurance, such as

tests, procedures, and doctor visits, as well as services or items associated with a trials

treatment.

Data collection time for that participant

Module 3 Summary

Congratulations! You have now completed Module 3: Choosing the Trials.You have learned

about

Several factors to consider when choosing clinical trials,

Several processes for evaluating trials, and

Potential sources of funding and reimbursement.

In the next module, well introduce the key members of your research team and methods for

training them in research practices.

Module 4: Building and Training the Research Team

In module 4, well discuss staffing and training your sites research team.


Identify the key members of a research team and define their responsibilities,

List tips for building a solid research team network, and

List strategies for training staff involved in a clinical trial.

The Core Research Team

Clinical trials require an onsite collaborati

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