How to Start a Clinical Research Study

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"My PI wants to conduct a clinical research study. Where do I begin?" Beginning a research study involves many steps and the following information is provided to assist clinical research personnel with the study start up activities.

Confidential Disclosure Agreements (CDA) are put in place before any confidential or proprietary information, such as a protocol, is released from CHOP. Alternatively, a pharmaceutical sponsor will not release a study protocol to a CHOP PI (Principal Investigator) until the PI signs a CDA.

For either scenario, the Office of Technology Transfer (OTT) must be contacted to negotiate the terms of this agreement. More information is provided on OTT's page.

Some questions your study team may want to consider before agreeing to do the clinical research study:

  • Is the protocol scientifically sound?
  • Do we have the study population?
  • How difficult will recruitment be?
  • Are there any competing studies?
  • Can we enroll the number of subjects requested in the allotted time frame of the study?
  • Will the study interfere with standard of care?
  • Are all of the procedures/tests outlined in the study appropriate?
  • Can we afford to do the study?
  • Will we be able to enroll subjects that meet each and every inclusion and exclusion criteria.
  • Are we an add-on site and is the study close to closing to accrual? If so, consider if it is worth the time and effort to start the study for the potential of only enrolling a few subjects or any at all.
  • Is the formulation of the drug age and weight appropriate? (eg, the drug is supplied only as a tablet and the age criterion is 1-3yrs old).

Examples which may prohibit an investigator from participating in a potential clinical research study:

  • There are 5 other studies recruiting the same subject population and we only see 5 children in a year with the condition being studied.
  • The entry criteria are too strict and we would not be able to enroll any subjects.
  • Recruitment will require study personnel to sit in the ED for 4 hours each day.
  • Study personnel must travel to other CHOP sites for subject recruitment and visits.
  • Otherwise healthy children would be required to have an in-patient stay.
  • Children are required to drink 20 mLs of the anti-emetic being studied.

All clinical studies done in collaboration with an external institution or sponsor require a contract or subcontract. The Technology Transfer Department and the Pre-Award Research Administration are responsible for negotiating these contracts and subcontracts.

Industry-sponsored trials:

Industry-sponsored studies require a contract known as a Clinical Trial Agreement (CTA) to be completed between the study sponsor, the study site Principal Investigator (PI) and the institution. All CTAs require institutional review and signature, as well as the signature of the CHOP PI.

 Technology Transfer will be alerted about a new study when Section 2.04 (Industry Study Requirements) is completed in eTRACK.

Key Reminders for industry-sponsored trials:

  • It is very important to initiate the budget and contract process in tandem with submitting for scientific and IRB approval. A study cannot commence until all institutional approvals (including a final CTA and budget) are in place.
  • Please remember that when amending your study through the IRB that the contract/budget may also need amending.

Investigator-Initiated Studies:

Typically, investigator-initiated studies require subcontracts with collaborating institutions. Pre-Award Research Administration facilitates this process and assists the research community with applying for, negotiating, and managing externally-sponsored research funding (government or Foundation grants, etc.). They also serve as a primary interface with federal and not-for-profit sponsors and with peer institutions that collaborate with CHOP researchers.

  • Work with your research business manager and or your division's administrative director to ensure sufficient funds are available to cover the cost of your trial and an appropriate agreement is in place.

Please see Pre-Award Research Administration for more information and how to find your Sponsored Projects Officers or Grant and Contracts Specialists.

Key Reminders for investigator-initiated studies:

  • It is very important to initiate the budget and contract process in tandem with submitting for scientific and IRB approval. A study cannot commence until all institutional approvals (including a final CTA and budget) are in place.
  • The IRB webpage contains helpful information on study protocol creation, including protocol templates.  For more information, please see Section 6, Compile IRB submission, below.
  • Please remember that when amending your study through the IRB that the contract/budget may also need amending.

It is important to ensure that the investigator has sufficient funds to conduct the proposed clinical research study. Clinical Trial Financial Management (CTFM) will be notified of all new studies requiring a budget once the study has been created in eTRACK.

eTRACK is a web based system for submission, routing, approval and management of clinical research studies. The goal of the system is to create an integrated, transparent system that serves as a single portal for all CHOP clinical research studies.

CTFM will work with you and your PI to create a final budget plan.

  • For industry-sponsored studies, CTFM will negotiate the budget with the sponsor.
  • For federally-funded and foundation-supported studies, CTFM is available to work with the research business manager to draft a proposed budget when there are patient care related costs.

Key Reminders
The IRB will not release the approved informed consent form until the budget plan is finalized and a Lawson number is assigned.

**A Lawson number is a unique internal identifier supplied by Specialized Accounting to facilitate the charging and management of a research grant. See below for more info on obtaining a Lawson number.

Effective June 1, 2008, independent scientific review will be required for certain protocols (defined below) prior to the CHOP IRB submission. Departments and Divisions have established appropriate committees to conduct these reviews in a timely manner.

The following types of protocols are exempt from scientific review by a CHOP scientific committee (except for when the IRB requests scientific review of a specific protocol):

  1. Protocol/grants peer-reviewed by a Federal-funding agency (e.g. NIH, CDC, DOD)
  2. Protocol/grants peer-reviewed by a national foundation (e.g. American Heart Association)
  3. Protocol/grants conducted by an industry sponsor
  4. Research that does not require direct involvement of human subjects (e.g. chart review or research exempt from IRB review)

For all other protocols, or for any protocol that the IRB specifically requests a separate review, internal scientific review should be conducted by one of the following:

  1. Existing CHOP or UPenn Scientific Review Committees (e.g. Cancer Center)
  2. Existing Divisional or Departmental Scientific Review Committees
  3. Scientific review committees constituted by or between Departments, Divisions, or Centers of Emphasis
  • Submit the scientific review form completed by an established scientific review committee together with the investigator response to the committee to the IRB at the time IRB submission.

Investigator Held IND/IDE Protocols Require Special Scientific Review

A separate scientific committee will provide scientific review for protocols that are being conducted under an investigator-held IND/IDE.  The IRB will not review your protocol without approval of this IND/IDE Scientific Review Committee.

To assist please review the Instructions for Scientific Review.

An IRB submission is required for any human subject research protocol. The CHOP IRB has implemented an electronic system for IRB submissions (eIRB). All new protocols submitted to the IRB must use the eIRB system.

The eIRB Help! section contains information to assist investigators, study coordinators and other users complete and work with the eIRB electronic IRB management system. eIRB has a Help section on every page but does not have room for illustrative examples or longer explanations. The IRB Office will continue to add new topics to this section as issues are identified.

The IRB templates and guidance are updated regularly; as such, it is important to refer to the IRB website prior to each submission to ensure that you are following the current procedures for IRB submission and that you have the most current protocol and informed consent form templates. Please see the following IRB homepage link (below) for more information. The IRB forms  contains helpful templates, including protocol templates that can be used by investigators in order to develop their study protocol. 

Key Reminders

  • It important to initiate the IRB submission process in tandem with submitting for contract and budget approval.
  • Pharmacy will receive a copy of the protocol via eIRB. It is helpful to meet with pharmacy once the study obtains IRB approval. Contact the Investigational Pharmacy.

Determine if your protocol requires approval from other CHOP review committees.

Please note that the eIRB system will automatically do the following:

  • Route all applications that involve radiation as part of the research procedures to the RDRC. Investigators need only indicate in eIRB Section 2.02 (1.0) and (2.0) that Radiology Review and Radiation Safety review are needed.
  • Route applications to the CHOP Biosafety Committee and Medical Device Committee.
  • Direct investigators to complete the CHPS application if the CHPS will be used during the study.

Center for Human Phenomic Science (CHPS)

The goal of the CHPS is to provide the resources and environment to support high-quality clinical research by qualified investigators. The CHPS grant to the hospital supports the facilities in which the research is conducted, the trained personnel necessary to support the investigator and offsets some of the costs for research tests and studies. The CHPS also provides administrative support to assist in solving the logistical problems of clinical research.

Protocols:
The CHPS at CHOP supports the important research endeavors of more than 75 different principal investigators in over 120 various research protocols. Approximately 20 divisions of Children's Hospital benefit from the services and support provided by this program. The wide scope of CHPS users is evident when reviewing our list of active protocols. To access the CHPS pages displaying lists of CHPS protocols and investigators, you must follow the "log in" instructions to become a registered CHPS website user.

Radiation Safety Committee - Human Subject Safety Review

If the human subjects involved in your study will receive radiation or radioactive substances of an investigational nature (i.e., exposure other than that given in standard nuclear medicine, diagnostic radiology, or radiation therapy procedures, or exposure resulting from standard procedure but independent of standard practice for patient care) a safety review is required.

All human subject protocols submitted to the CHOP Institutional Review Board (IRB) for review must be reviewed and approved by the UP-Radioactive Drug Research Committee (RDRC) of the University of Pennsylvania if they meet the following criterion:

Use of radioactive materials and energized equipment for research purposes at CHOP is managed through a contract with the University of Pennsylvania's Environmental Health and Radiation Safety office (UP-EHRS). Basic and clinical research activities involving radioactive materials/ionizing radiation must be appropriately registered with UP-EHRS. UP-EHRS' policy on radiation safety states that the philosophy of the program is to maintain all radiation exposures As Low As Reasonably Achievable (ALARA).

UP-Radiation Safety Office
32nd and Chestnut
(215) 898-7187[|#]


The UP-RDRC review must occur simultaneously with the review of the IRB. The UP-RDRC is administered by UP-EHRS. The Radiation Safety Office should be contacted directly regarding the guidelines for protocol submission, including, but not limited to:

  • Informed consent
  • Risk / Benefit
  • Procedures with exposures less than: 3 rads (total body) per study and 5 rads (total
    body) per year or 5 rads (per organ) per study and 15 rads (per organ) per year.
  • Procedures with exposures greater than: 3 rads (total body) per study and 5 rads
    (total body) per year and 5 rads (per organ) per study and 15 rads (per organ) per
    year.
  • Procedures that use X-rays only.
  • Procedures that use Radioactive Materials (RAM) only.
  • Procedures using both RAM and X-ray.

Any revisions or modifications required by the RDRC must be incorporated into the protocol submitted to the IRB before full approval is given.

All protocols involving radioactive materials must be submitted for full IRB review.

Radiology Scientific Review Committee - for Review and Approval of Radiology Research Services

Any study requiring a physician or service from the Department of Radiology must be approved by the Radiology Scientific Review Committee (RSRC) and the Radiology Research Committee. In the eIRB application, complete Section 2.02 - Study Required Approvals: Radiology. Once submitted to the IRB and in eTRACK, the study will automatically be directed to the Radiology Research Committee for radiology ancillary approval.

This includes:

  • X-Ray
  • CT
  • Interventional Radiology
  • MEG
  • MRI
  • Nuclear Medicine
  • Ultrasound
  • Database utilization
  • Professional readings

Depending on the type of the study and funding source the submission may or may not undergo a full review. It is important to include the name of the radiologist co-investigator if there is one in the submission. If there is no radiologist co-investigator, state none. Once the study has been reviewed, the ancillary approval will be directly submitted online or in case of questions or full review the principal investigator or research coordinator will be contacted.
If there are any questions please contact the assistant to the Chairman of the Radiology Scientific Review Committee.

Once the study is approved by the RSRC, Clinical Trials Finance Management will include these services in the budget plan and negotiations. Questions regarding the billing plan can be addressed to Clinical Trials Finance Management.

Once radiology ancillary approval has been granted, a Radiology Billing Analyst will request a Start Up Meeting with the study team and specific radiology service area staff to review the following:

  • Study specific requirements
  • Study specific radiology information
  • Scheduling
  • Billing
  • Radiology will create a study specific and patient specific Radiology Request Form
    • This form is to be give to the Radiology Technician at the time of the test

Institutional Biological Safety Committee (IBC) - If your study involves recombinant DNA, gene therapy, or human blood/tissue collection

The Institutional Biological Safety Committee (IBC) is responsible for:

  • Formulation of policy and procedure related to the use of recombinant DNA and biohazardous agents including: human pathogens, human blood and body fluids, oncogenic viruses, and all other infectious agents.
  • Review and approval of work involving the generation of recombinant DNA, gene therapy and the formation of transgenic animals, as mandated by the National Institutes of Health.
  • Maintaining an updated register of biohazardous agents used within The Children's Hospital of Philadelphia Research Institute facilities.
  • Review and approval of the safe practices and procedures for work with potentially infectious materials and recombinant DNA. All potentially infectious materials and recombinant DNA to be used in the labs or by staff must be registered with and approved for use by the IBC.

Please note: If your PI is going to process any human samples (blood, blood products, tissue, cell lines) in his/her lab, they must resister their work with the IBC using a Human Source Material Registration form.  Contact the IBC to request this form. 

Oncology Pediatric Protocol Review Committee (PPRC)

All oncology protocols and protocols conducted by investigators within the Division of Oncology (with some exceptions) must be reviewed by the PPRC.

PPRC uses an electronic submission (eSubmission) process. Protocols are submitted using the following link: PPRC portal

Medical Device Committee

Prior to evaluation, purchase or use of all new medical devices, products or equipment, the Medical Device Committee of Supply Chain's CHOPtimize Program, reviews and approves all items that introduce either new technology or change to existing technology to the organization.

Any device or machine not currently used at CHOP needs to be reviewed by the device committee. This includes blood pressure machines, ECG machines, medication delivery pumps, or any type of equipment used on patients that is not currently used in the hospital for clinical care.

  1. Complete appropriate section (8.02 Device Information) of the eIRB application pertaining to an Investigational Device.  
  2. Contact the Office of IND/IDE Support for guidance on IDE exemption.
  3. Once you complete Section 8.02, Device Information, in the eIRB application, print out a copy and send to the CHOPtimize Program. Once the request is received, they will work with the requestor(s) and schedule an appearance at the next Medical Device Committee meeting. 

Please note: Plan accordingly. The Medical Device Committee meets once a month.

Please note:  Any external machine provided by sponsor (ex ECG machine, medication infusion pump) for a clinical study must be approved by the Biomedical Engineering Department. For more information, contact the BioMedical Engineering Department.

It is important to stay in close communication with the CHOP personnel negotiating your contract and budget to ensure that there is no problems and that the negotiations occur as quickly as possible. In cases where contract and/or budget negotiations are delayed, it is helpful to have a meeting with the Office of Technology Transfer, Pre-Award Research Administration and/or Clinical Trials Financial Management to discuss what issues/language are causing the delay. In some cases input from your PI can help move negotiations forward.

  • No subjects may be enrolled on your clinical study prior to a fully executed contract (with budget) being in place.

Regulatory Binder

You should begin putting together a regulatory binder for your trial.

The Regulatory binder is the central file for all required regulatory documents relating to the study. The following provides a list of documents that should be kept in your regulatory binder. The order of the sections can vary depending on your study, but it is generally easier to keep the most frequently used sections closer to the beginning of the binder. In many cases it may be more convenient to use more than one binder to hold all the documents. Careful labeling of the binders and an organized tabular system will keep your files well organized.

Contents of the Regulatory Binder:

  1. Protocol
    • Protocol
    • Protocol Signature Page
    • Protocol Amendments
  2. Signature and Delegation of Responsibility Log
  3. Informed Consent
    • Copy of current approved informed consent form (ICF).
      Note: This should be clearly marked as the current version
    • All version of the approved ICF (original and all revised versions)
    • IRB approved education materials and advertisement
  4. Correspondence with the IRB
  5. Subject Logs including screening and enrollment logs
  6. Adverse Events
  7. Sample Case Report Forms
  8. Monitoring Logs and reports
  9. Curricula Vitae and Licenses
  10. Laboratory Documents including certifications, licenses, normal reference ranges
  11. General Correspondence
     

For Drug and Device Studies the following are also included:

  1. FDA Form 1571 for sponsor-investigators
  2. FDA Form 1572
  3. Investigators Brochure and Product Labeling
  4. Drug/Device Accountability Logs
  5. Contract
  6. Salaries and Grant funding documents
  7. Financial Disclosure

FINANCIAL DOCUMENTS: DO NOT include Financial Documentation in the Regulatory Binder. Store financial documentation in a separate secure location

Clinical Trials Operation Manual

It is recommended that a reference binder or clinical trials operations manual (CTOM) be prepared for each of your trials. This should include specific details about all steps/process, etc. necessary to conduct your trial. In the event that you are out of the office another member of your team should be able to use this CTOM and know exactly what to do as your backup.

Visit the CTO Forms Page to access the CTOM Instructions and Templates.

A key name is a unique internal identifier supplied by the Institutional Review Board (IRB) to allow for cross departmental tracking of a protocol.

The Key Name consists of:

  • Principal Investigator's last name
  • Principal Investigator's first initial
  • Year study was created
  • Six digit study number (presently most study numbers are 4 digits, place zeros before the study number to make it six digits).
  • Example: DoeJ_07-001234

Once the study is reviewed by the IRB, you will receive an e-mail from the IRB with on of the following notices: approval, deferral, approvable with contingencies or non approvable as written.

In most cases feedback is approvable with contingencies. In this case, you must address the contingencies within 90 days of receipt and resubmit to the IRB.

Please note: If the protocol and/or informed consent document are changed as a result of IRB feedback, the final approved protocol and consent form must be sent to the contracts and budget groups in case the changes impact either the budget or contract.

Congratulations on receiving IRB approval!

All studies with any type of funding will have a Lawson number issued by Specialized Accounting. This allows charges to be applied to the study account.


A Lawson number will not be released until the study contract and budget have been approved and fully executed by the Office of Technology Transfer.

To obtain a Lawson Number:

  • For Industry Studies, the Lawson Number will be assigned in eTRACK by Specialized Accounting.
  • For all other studies you will have to contact the research business manager as the Lawson Number will be assigned in eSPA by Specialized Accounting.

It is the responsibility of the study team to make sure they have obtained and are keeping record of their Lawson number before starting a study.

For questions regarding Lawson numbers for Federal Studies, please contact your Research Business Manager

For questions regarding Lawson numbers for Industry Studies, please contact CRAnalyst

Once you have your approved IRB number (aka Key name), and Research Finance assigned Lawson Number, the eTRACK system automatically sends the study to be built in EPIC. You will be able to tell if the study has been built in EPIC by going to the study workspace in eTRACK and looking under the history tab. If you see "EPIC Study Setup Confirmed", your study has been built in EPIC.

By creating your study in EPIC this will assure that the correct study information is available to be attached to your patient and to the visit so that the research billing process can occur.

Any questions should be directed to the assigned Clinical Research Financial Analyst (CRFA) listed in the study workspace.

View a robust compliance guide detailing how EPIC could support an organization’s overall 21 CFR Part 11 compliance efforts.

Industry sponsors typically conduct an initiation visit prior to study start. In many cases the study coordinator is responsible for working with the sponsor to set up this visit.

It is recommended that the entire study team meet and conduct a mock run through of the first patient visit to identify any potential problems prior to actually enrolling the first subject.

Good Luck with your study!