Primer: Clinical Trial Basics: What You Need to Know to Manage an Industry Sponsored Clinical Trial

Presenters:

Cheryl K. Williams, Associate Director, Office of Research and Project Administration, University of Rochester

Donna Galloway, Division Administrator, Infectious Diseases Division, University of Rochester

Doreen M. Francis, RN, CCRC, Vaccine Research Unit, Infectious Diseases Division, University of Rochester

Milestones in Clinical Trial and Ethics Development1

Research Ethics MilestonesPresidents Council on Bioethics

2000National Bioethics Advisory

Commission

1990Common RuleCIOMS GuidelinesHHS/FDA Human Subject Regulations

1980Belmont Report

Trigger Events

Gene Transfer Subject Death

The Syphilis Study (Expose)

Research Ethics Milestones

1970

Declaration of Helsinki

Kefauver-Harris Amendments 1960

1950Nuremberg Code

1940

1930

Trigger Events

The Beecher Article (NEJM)

Milgram StudyThe Thalidomide TragedyHuman Radiation Experiments (begin)

The Nazi Experiments

The Syphilis Study (begins)1Dunn, C.M., Chadwick, G.L. Protecting Study Volunteers in Research, Third Edition, p 27,

(2004)

Game Changers in Clinical Trials

• Nazi Concentration Camp Atrocities• The Milgram Study – Obedience Study• The Thalidomide Catastrophe – Sedative • PHS Study of Untreated Syphilis in the Negro

Male• Human Radiation Experiments – Plutonium

Injections – Intentional Releases of Radiation• U Penn Gene Transfer Experiment - FCOI

Harmonization

Ideally, your institution has a central office to review, negotiate and approve clinical trials

Reality:• Central sponsored programs office negotiates clinical

trial agreement (CTA)• IRB reviews, approves protocol and ICF• Department reviews, negotiates budgetPossible Result: contradictory documents and bad

timing – CTA negotiated, but IRB approval Missing or budget still under review

You Know You’re Going to Work on a Clinical Trial When . . .

1. Your PI brings a Confidential Disclosure Agreement (CDA) to you

2. Your PI starts talking about the patient base3. Your PI leaves town to go to an investigators’

meeting in the Caribbean 4. An unacceptable budget with an

exceptionally expensive protocol lands on your desk

The CDA – see Handout 1 for sample

Should be reviewed by your central office• Concerns:

1. Definition of confidential information – narrow the scope – eliminate any mention of intellectual property requirements – this is a CDA only

2. Time limit to hold confidential – 1 year standard (obligation no greater than 5-7 years)

3. Only the PI should be bound by agreement

The CDA

Should be reviewed by your central office• Concerns:

4. If a CTA results, it will supersede the CDA5. Believe it or not, Export Control – don’t accept any

information that could be subject to this law6. Refuse to receive any trade secrets7. Governing law

The CTA – see Handout 2 for sample

Negotiated by the Central OfficeIssues:1. CTA with Institution, not PI2. Signatories should be sponsor, Institution, with

PI signing as “read and understood”3. Statement of work section should reference

attached protocol4. Payment terms should reference attached

negotiated budget

The CTA

5. Sponsor will supply drug/devise in sufficient quantity

6. Investigator and sponsor assure that study will be conducted in accordance with all laws and regulations

7. HIPAA8. In an age of electronic everything, watch out

for CFR, Title 21, Part 11, Electronic Records compliance

The CTA

9. Time limitation on requirement to keep confidential10.Under data ownership and IP, make sure all original

records or work, including patient medical records, laboratory records and reports scans, films and pre-existing information in Institution’s databases remain Institution property – everything else belongs to sponsor

11.Free to publish after sponsor review12.Site access – know what your institution will accept

The CTA

16.Subject Injury – sponsor reimburses institution for cost of reasonable and customary medical treatment for any illness or injury sustained by subject

17.Insurance – get sponsor’s limits – remember, indemnification and subject injury are not limited by sponsor’s insurance limits

18.AAHRPP language, if required by your institution

The CTA

19.WARRANTIES – institution should make no warranties, express or implied regarding the results

20.Governing law – should be your state’s

The Protocol and Informed Consent Form

• Protocol – Provided by sponsor – Usually in final version– Review for feasibility to assist in budget

preparation and to compare with consent

The Protocol and Informed Consent Form• Consent– Template provided by sponsor– Modifications per institutional policy

• SOP for Consent Process– Consent quiz used to confirm subject

understanding and tool to aid discussion – see Exhibit C

Other Considerations

• Protocol may need to be reviewed by others: Institutional Biosafety, ED Committee or other department review

• Applications to be completed– 2 at our institution

• Local IRB• WIRB

– IBC– Research Match– Other committee-required applications

Other Documents

• Consent quiz (see Handout 3 for sample)• Phone screen• Advertisements– Email/internet– Newspaper/flyer– Radio TV spots

• 1572

Other Documents

• CV Assembly/Medical Licenses• Financial Disclosure form• Conflict of Interest statements– COI Management Plan if applicable

Other Coordinator Duties

• Set up any testing need with appropriate dept– Lab– X-ray– Cardiology, etc.

• All this information must be in the budget!

The Budget

• Event grid – used to develop budget• Event grid - populated with time and costs– Nurse time has been rounded (salary and benefits)

to $50/hr)– PI time at $200/hr

• Bullet list of pass-through costsSee Handout 4 for samples