SSA_Investigator Registration_12-15-09

SUPPORTING STATEMENT A FOR:

INVESTIGATOR REGISTRATION AND FINANCIAL DISCLOSURE FOR INVESTIGATIONAL TRIALS IN CANCER TREATMENT

(NCI)

SUBMITTED BY:

PHARMACEUTICAL MANAGEMENT BRANCH, CTEP, DCTD

NATIONAL CANCER INSTITUTE

December 15, 2009

Hall, Charles L., RPh. MS

Branch Chief

Pharmaceutical Management Branch, CTEP, DCTD, NCI

Executive Plaza North, Room 7149

9000 Rockville Pike

Bethesda, MD 20852

(301) 496‑5725

FAX: (301)402‑0429

[email protected]

TABLE OF CONTENTS

A. Justification 1

A.1 Circumstances making the collection of information necessary 1

A.2 Purpose and use of the information collection 2

A.3 Use of improved information technology and burden reduction 3

A.4 Efforts to identify duplication and use of similar information 3

A.5 Impact on small business or other small entities 5

A.6 Consequences of collecting the information less frequently 5

A.7 Special circumstances relating to the guidelines of 5 CFR 1320.5 5

A.8 Comments in response to the Federal Register notice and efforts to consult outside agency 5

A.9 Explanation of any payment or gift to respondents 6

A.10 Assurance of confidentiality provided to respondents 6

A.11 Justification for sensitive questions 7

A.12 Estimates of annualized burden hours and costs 8

A.13 Estimates of other total annual cost burden to respondents and record keepers 9

A.14 Annualized cost to the federal government 9

A.15 Explanation for program changes or adjustment 9

A.16 Plans for tabulation and publication and project time schedule 10

A.17 Reason(s) display of OMB expiration date is inappropriate 10

A.18 Exceptions to certification for paperwork reduction act submissions 10

List of Attachments

Attachment 1. Statement of Investigator (FDA Form 1572 modified)

Attachment 2. Supplemental Investigator Data Form

Attachment 3. Financial Disclosure Form

Attachment 4. NIH Privacy Act Memo

Attachment 5. Office of Human Subjects Review (OHSR) Review Email

A. Justification

A.1 Circumstances making the collection of information necessary.

The National Cancer Institute (NCI) is requesting OMB approval under the Paperwork Reduction Act (44 U.S.C. 3501 et seq.) for the reporting and record keeping requirements contained in the FDA regulation “Investigational New Drug Application” (21 CFR Part 312) specifically as it pertains to the registration of investigators who participate in NCI sponsored protocols. The National Cancer Institute (NCI) fosters drug development to benefit cancer patients and as an Investigational New Drug (IND) sponsor is required to select only investigators qualified by training and experience as appropriate experts to investigate the drug. The Food and Drug Administration (FDA) has numerous requirements for sponsors specified in 21 CFR Part 312.53. These regulations require sponsors to obtain information from the investigator. Before permitting an investigator to begin participation in an investigation the sponsor shall obtain the following:

1. a signed investigator statement (Form FDA 1572)

2. Curriculum vitae, and

3. Financial disclosure information

The information collected on the NCI modified FDA Form 1572 is similar to that collected by the FDA. However, the NCI version provides guidance to the investigator to facilitate the completion of the form. The FDA has allowed the NCI to use a different process for collection and revision of the data due to the unique manner in which the NCI conducts studies compared to other sponsors. The Cancer Therapy Evaluation Program collaborates with other programs within the NCI to collect registration data for their trials. This joint process reduces duplication and provides a consistent procedure within those programs of the National Cancer Institute.

This OMB submission is being presented as an “Existing Collection in Use without an OMB Number.”

A.2 Purpose and Use of the Information Collection

NCI uses the data from:

Form FDA 1572 (modified due to annual submission rather than on a protocol by protocol basis) (see Attachment 1)

Supplemental Investigator Data Form (see Attachment 2)

Financial Disclosure Form (see Attachment 3)

Curriculum vitae

These data forms ensure compliance with NCI's responsibilities as an IND sponsor. The FDA can request copies of these forms at any time for audit and review. Record keeping of investigator registration and financial disclosure data in a standard format is required to track compliance and to allow an investigator to receive, and continue to receive NCI‑sponsored drugs. The NCI does not establish a standardized format for submission of the Curriculum vitae (CV) but allows the investigator to submit the information in the any configuration they chose. This requirement is an essential part of investigator accountability process and motivates them maintain accurate, appropriate records. The record keeping retention period is specified by FDA regulation, and the NCI does not deviate from that requirement. As noted above, the FDA requires IND sponsors to maintain adequate records on the shipment and disposition of drugs to investigators.

A.3 Use of Improved Information Technology and Burden Reduction

The use of improved information technology techniques has been considered. One element of the FIREBIRD initiative is the incorporation of this information into an electronic database that integrates the submissions of the public and private sectors. This project is currently under development by the FDA, NCI, and private industry, however is not currently in use for this information collection.

There is an IT system associated with the Investigator Registration (IR) process.  Data is extracted into a Registration Module in an Enterprise system and a pilot program is underway. The pilot program involves scanning some IR documents into a database.  It is hoped that this pilot program will facilitate the implementation of either an online registration process or a 100% electronic storage for documents. A Privacy Impact Assessment (PIA) has been submitted and is being reviewed by NIH. The IT system is titled, “Investigator Registration.”

A.4 Efforts to Identify Duplication and Use of Similar Information

The NCI procedure is so different (annual submission) compared to the FDA process (per protocol submission) that the NCI feels that it is important that CTEP pursue approval of a separate document. The FDA utilizes a similar form and mechanism to collect this information from other sponsors of investigational trials.  The FDA process is significantly different in that the investigator registration portion is a very small part of the Investigational New Drug Application process. The information and method utilized by the FDA requires significantly greater burden to the investigators who complete the forms and the government who review and retain the forms. More than 25 years ago the FDA and the NCI established a modified submission and retention procedure for investigator registration and financial disclosure information. Whereas the agency (FDA) requires other sponsors to submit this information on a protocol by protocol basis, the NCI collects this data annually. This was done to reduce the administrative burden on the individual NCI registered investigators since they often participate in numerous trials simultaneously. The difference between the FDA version of the FDA Form 1572 and the NCI version is the addition of pre-populated statements in Blocks 6 (see Attachment 1):

N/A-The Cancer Therapy Evaluation Program, National Cancer Institute requires each investigator to submit a separate FDA Form 1572, CV, Supplemental Data Form, and Financial Disclosure Form. The information entered in this section will NOT be entered in the CTEP NCI database.

and Block 7 of the Form FDA 1572 to account for the annual submission of data.

I am participating in Cancer Therapy Evaluation Program (CTEP), National Cancer Institute-sponsored clinical trials. I understand that this single FDA Form 1572 will cover my participation in all (one or more) clinical trials under CTEP sponsorship (IND and/or funding). I also understand that I am responsible for meeting all the requirements for clinical trials specified by this signed FDA Form 1572 for EACH CTEP clinical trial in which I participate.

Regarding the Supplemental Investigator Data Form (see Attachment 2) and Financial Disclosure Form (see Attachment 3), the FDA does not specify a specific form for collection of this essential data.   These forms were developed to fill the void created by the FDA requirement. The NCI procedure has been in place and met all of the regulatory requirements for more than 25 years. CTEP has built an extensive submission and tracking process around the annual submission procedure because we feel that this provides the most current data. Any changes to the existing process will require a major change in the form retention and retrieval mechanism as well as the business processes at NCI. A change will increase the burden to both the investigator and the government.  

A.5 Impact on Small Business or Other Small Entities

Data collection for investigator registration involves primarily Hospitals, Universities and Cancer Centers, which are not small businesses. In some instances it involves physicians in private practice who participate in NCI sponsored investigational studies but the number is very small.

A.6 Consequence of Collecting the Information Less Frequently

The investigator registration and financial disclosure information is collected annually. This frequency was been acceptable to the NCI and the FDA for 25 or more years with the justification that it adequately reflects changes in the investigator status, financial changes and shipping requirements. Investigators notify the NCI when there are significant changes within the one year period.

A.7 Special Circumstances Relating to the Guidelines of 5 CFR 1320.5

No special circumstances inconsistent with the guidelines in 5CFR 1320.5 are known.

A.8 Comments in Response to the Federal Register Notice and Efforts to Consult Outside Agency

Federal Register Notice

The 60-Day Federal Register Notice of the proposed data collection was published on June 10, 2009, Vol. 74, Page 27552. One public comment was received regarding pharmaceutical testing and the submitter responded to the email.

Consultations

More than 25 years ago the FDA and the NCI established a modified submission and retention procedure for investigator registration and financial disclosure information. Whereas the agency (FDA) requires other sponsors to submit this information on a protocol by protocol basis, the NCI collects this data annually. This was done to reduce the administrative burden on the individual NCI registered investigators since they often participate in numerous trials simultaneously. The difference between the FDA version of the FDA Form 1572 and the NCI version is the addition of pre-populated statements in Blocks 6 and 7 (see Attachment 1 and paragraph A.4).

A.9 Explanation of Any Payment or Gift to Respondents

Respondents will not receive any payment or gift for answering the questions.

A.10 Assurance of Confidentiality Provided to Respondents

The release of information submitted to the NCI as part of the Investigator Registration/Financial Disclosure process is compliant with current regulatory requirements. The information is made available to the IND sponsor and to FDA upon request to meet regulatory requirements 21 CFR Part 312.64(d). Investigators are made aware of their legal requirements when they complete Form FDA‑1572 and the Investigator Supplemental Data form by which they become eligible to use investigational new drugs. Consistent with 21 CFR Part 312.62, the investigators or their designees retain the forms for a period of 2 years following the date a marketing application is approved for the drug for the indication for which it is being investigated and closure of the NCI IND. However, if no application is to be filed or if the application is not approved for such indications, the records must be retained until 2 years after the NCI IND closure and FDA is notified.

The current records in this data system are being covered by NIH Privacy Act system of records, 09-25-0200, “Clinical, Basic and Population-based Research Studies of the National Institutes of Health (NIH) HHS/NIH/OD.” At this time, a new system of records is being developed and once it is finalized then it will be used to cover the records in this data system (see revised Attachment 4).

The Office of Human Subjects Research (OHSR) was contacted to see if this data collection required review. OHSR concluded it does not need to be reviewed because it is not considered research (see Attachment 5).

A. 11 Justification for Sensitive Questions

Personally identifiable information (PII) is being collected in the form of education, date of birth and UPIN of the investigator, and financial disclosure information. This information is necessary to meet regulatory requirements established by the FDA and to clearly establish the identity of investigators where there are similar or identical names. It also ensures that the investigator has completed required training, is licensed and practicing in the field of expertise in which the research is conducted. The collection and evaluation of this information by the NCI is required by the FDA of NCI as sponsor and protects the health and safety of patients who participate in investigational trials.

A. 12 Estimates of Annualized Burden Hours and Costs

The annualized respondent's burden for record keeping is estimated to require 8,564 hours for the Statement of Investigator, Supplemental Investigator Data Form and the Financial Disclosure Form (see Table A.12-1). A total number of 17,128 investigators are anticipated to complete all three forms. Over the three-year data collection period, the total burden is estimated at 25,692 hours. An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number.

Table A.12-1 Estimates of Annual Burden
Type of Respondents	Form	Number of Respondents	Frequency of Response	Average Time per Response	Total Hour Burden
Investigators and Designee	Statement of Investigator	17,128	1	0.25 (15 minutes)	4,282
	Supplemental Investigator	17,128	1	0.167 (10 minutes)	2,855
	Financial Disclosure	17,128	1	0.083 (5 minutes)	1,427
Totals		17,128			8,564

The annualized cost burden to the respondents is estimated at $513,840 (see Table A.12-2). The record-keeping burden represents an average time required for entries (30 minutes) on the three documents listed below. The total cost is estimated at $1,541,520.00 over the course of the three-year information collection. These estimates are based on the number of investigators supported by PMB. Cost estimates are based upon burden hours at an average cost of $60.00 per hour. This estimate reflects the routine practice by the investigators to have administrative personnel complete the form followed by verification and signature by the investigator. The estimate is also based on FDA estimates of an industry average for preparing and submitting collected information. For re-registration the NCI sends forms pre-populated with the current data for the investigator to review, modify if required and sign. This practice dramatically reduces the burden to the investigator.

Table A.12-2 Annualized Cost to Respondents
Type of Respondents	Form	Total Hour Burden	Wage Rate per Hour	Respondent Cost
Investigators and Designee	Statement of Investigator	4282	$60	$256,920.00
	Supplemental Investigator	2855	$60	$171,280.00
	Financial Disclosure	1427	$60	$ 85,640.00
Total		8564		$513,840.00

A. 13 Estimates of Other Total Annual Cost To Respondents and Record Keepers

There is no additional cost burden to the respondents and record keepers.

A. 14 Annualized Cost to the Federal Government

The annualized cost to the Federal government for collecting, evaluation, sorting, entering into a tracking database, storing and coordinating annual renewal requires 9 FTEs at an estimated $795,000.

A. 15 Explanation of program Changes or Adjustments

This information collection is an “Existing Collection in Use without an OMB Number.”

A. 16 Plans for Tabulation and Publication and Project Time Schedule

There are no plans to publish this data for statistical use.

A.17 Reason(s) Display of OMB Expiration Date is Inappropriate

The date will appear on all forms and information.

A.18 Exceptions to Certification for Paperwork Reduction Act Submissions

No exceptions to the certification statement are required by this information collection.

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