Federal Register: February 19, 2004 (Volume 69, Number 33)
DOCID: FR Doc 04-3488
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
Docket ID: [Docket No. 2003N-0360]
DOCUMENT ACTION: Notice.
Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Information Program on Clinical Trials for Serious or Life-threatening Diseases: Maintaining of a Databank
DATES: Fax written comments on the collection of information by March 22, 2004.
The Food and Drug Administration (FDA) is announcing that a proposed collection of information has been submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995.
Agency information collection activities; proposals, submissions, and approvals,
In compliance with 44 U.S.C. 3507, FDA has submitted the following proposed collection of information to OMB for review and clearance. Information Program on Clinical Trials for Serious or Lifethreatening Diseases: Maintaining a Databank (OMB Control Number 09100459) Extension
In the Federal Register of March 18, 2002 (65 FR 12022), FDA issued a guidance to industry on recommendations for investigational new drug application (IND) sponsors on submitting information about clinical trials for serious or lifethreatening diseases to the Clinical Trials Data Bank developed by the National Library of Medicine, National Institutes of Health (NIH). This information is especially important for patients and their families seeking opportunities to participate in clinical trials of new drug treatments for serious or lifethreatening diseases. The guidance describes the following three collections of information: (1) Mandatory submissions, (2) voluntary submissions, and (3) certifications.
II. Mandatory Submissions
Section 113 of the Food and Drug Administration Modernization Act of 1997 (the Modernization Act) (Public Law 105115) requires that sponsors shall submit information to the Clinical Trials Data Bank when the clinical trial: (1) Involves a treatment for a serious or life threatening disease and (2) is intended to assess the effectiveness of the treatment. The final guidance discusses how sponsors can fulfill the requirements of section 113 of the Modernization Act. Specifically, sponsors should provide the following: (1) Information about clinical trials, both federally and privately funded, of experimental treatments (drugs, including biological products) for patients with serious or lifethreatening diseases; (2) a description of the purpose of the experimental drug; (3) patient eligibility criteria; (4) the location of clinical trial sites; and (5) a point of contact for patients wanting to enroll in the trial. Senate 1789, ``Best Pharmaceuticals for Children Act'' (BPCA) (Public Law 107109) established a new requirement for the Clinical Trials Data Bank mandated by section 113 of the Modernization Act. Information submitted to the data bank must now include ``* * * a description of whether, and through what procedure, the manufacturer or sponsor of the investigation of a new drug will respond to requests for protocol exception, with appropriate safeguards, for singlepatient and expanded protocol use of the new drug, particularly in children.'' The final guidance will be updated to include a discussion of how sponsors can fulfill the BPCA requirements. III. Voluntary Submissions
Section 113 of the Modernization Act also specifies that sponsors
may voluntarily submit information pertaining to results of clinical
trials, including information on potential toxicities or adverse effects associated with the use or administration of the
investigational treatment. Sponsors may also voluntarily submit studies that are not trials to test effectiveness, or not for serious or life threatening diseases, to the Clinical Trials Data Bank.
Section 113 of the Modernization Act specifies that the data bank will not include information relating to a trial if the sponsor certifies to the Secretary of Health and Human Services (the Secretary) that disclosure of the information would substantially interfere with the timely enrollment of subjects in the investigation, unless the Secretary makes a determination to the contrary.
Description of Respondents: A sponsor of a drug or biologic product regulated by the agency under the Federal Food, Drug, and Cosmetic Act or section 351 of the Public Health Service Act (42 U.S.C. 262) who submits a clinical trial to test effectiveness of a drug or biologic product for a serious or lifethreatening disease.
Burden Estimate: The information required under section 113(a) of
the Modernization Act is currently submitted to FDA under 21 CFR part
312, and this collection of information is approved under OMB control
number 09100014 until January 31, 2006, and, therefore, does not
represent a new information collection requirement. Instead,
preparation of submissions under section 113 of the Modernization Act
involves extracting and reformatting information already submitted to
FDA. Procedures (where and how) for the actual submission of this
information to the Clinical Trials Data Bank are addressed in the
guidance. The Center for Drug Evaluation and Research (CDER) received
3,957 new protocols in 2002. CDER anticipates that protocol submission
rates will remain at or near this level in the near future. Of these
new protocols, an estimated twothirds\1\ are for serious or life
threatening diseases and would be subject to either voluntary or
mandatory reporting requirements under section 113 of the Modernization
Act. Twothirds of 3,957 protocols per year is 2,638 new protocols per
year. An estimated 50 percent\1\ of the new protocols for serious or
lifethreatening diseases submitted to CDER are for clinical trials
involving assessment for effectiveness, and are subject to the
mandatory reporting requirements under section 113 of the Modernization
Act. Fifty percent of 2,638 protocols per year is 1,319 new protocols
per year subject to mandatory reporting. The remaining 2,638 new protocols per year are subject to voluntary reporting.
\1\ Estimate obtained from a review of 2,062 protocols submitted to CDER between January 1, 2002, and September 20, 2002.
The Center for Biologics Evaluation and Research (CBER) received
910 new protocols in 2002. CBER anticipates that protocol submission
rates will remain at or near this level in the near future. An
estimated twothirds of the new protocols submitted to CBER are for
clinical trials involving a serious or lifethreatening disease, and
would be subject to either voluntary or mandatory reporting
requirements under section 113 of the Modernization Act. Twothirds of
910 new protocols per year is 607 new protocols per year. An estimated
50 percent\1\ of the new protocols for serious or lifethreatening
diseases submitted to CBER are for clinical trials involving
assessments for effectiveness. Fifty percent of 607 protocols per year
is an estimated 304 new protocols per year subject to the mandatory
reporting requirements under section 113 of the Modernization Act. The
remaining 606 new protocols per year are subject to voluntary
reporting. The estimated total number of new protocols for serious or
lifethreatening diseases subject to mandatory reporting requirements
under section 113 of the Modernization Act is 1,319 for CDER plus 304
for CBER, or 1,623 new protocols per year. The remainder of protocols
submitted to CDER or CBER will be subject to voluntary reporting,
including clinical trials not involving a serious or lifethreatening
disease as well as trials in a serious or lifethreatening disease but
not involving assessment of effectiveness. Therefore, the total number
of protocols (4,867) minus the protocols subject to mandatory reporting
requirements (1,623) will be subject to voluntary reporting, or 3,244
protocols. Our total burden estimate includes multicenter studies and
accounts for the quality control review of the data before it is
submitted to the data bank. The number of IND amendments submitted in
2002 for protocol changes (e.g., changes in eligibility criteria) was
4,750 for CDER and 1,646 for CBER. The number of IND amendments
submitted in 2002 for new investigators was 9,419 for CDER and 1,773
for CBER. The number of protocol changes and new investigators was
apportioned proportionally between mandatory and voluntary submissions.
We (FDA) recognize that single submissions may include information
about multiple sites. Generally, there is no submission to FDA when an
individual study site is no longer recruiting study subjects. For this
analysis, we assumed that the number of study sites closed each year is
similar to the number of new investigator amendments received by FDA
(9,419 CDER and 1,773 CBER). Generally, there is no submission to FDA
when the study is closed to enrollment. We estimate the number of
protocols closed to enrollment each year is similar to the number of
new protocols submitted (3,957 CDER and 910 CBER). The hours per
response is the estimated number of hours that a respondent would spend
preparing the information to be submitted under section 113(a) of the
Modernization Act, including the time it takes to extract and reformat
the information. FDA has been advised that some sponsors lack
information system capabilities enabling efficient collection of
companywide information on clinical trials subject to reporting
requirements under section 113(a) of the Modernization Act. The
estimation of burden under section 113(a) reflects the relative
inefficiency of this process for these firms. Based on its experience
reviewing INDs, consideration of the information previously presented,
and further consultation with sponsors who submit protocol information
to the Clinical Trials Data Bank, FDA estimated that approximately 4.6
hours on average would be needed per response. The estimate
incorporates 2.6 hours for data extraction and 2.0 hours for
reformatting based on data collected from organizations currently
submitting protocols to the Clinical Trials Data Bank. We considered
quality control issues when developing the current burden estimates of
2.6 hours for data extraction and the 2.0 hours estimated for
reformatting. Additionally, the internetbased data entry system
developed by NIH incorporates features that further decrease the
sponsor's time requirements for quality control procedures. The
Clinical Trials Data Bank was set up to receive protocol information
transmitted electronically by sponsors. Approximately 10 percent of
sponsors electronically transmit information to the Clinical Trials
Data Bank. If the sponsor chooses to manually enter the protocol
information, the data entry system allows it to be entered in a uniform
and efficient manner primarily through pulldown menus. As sponsor's
familiarity with the data entry system increases, the hourly burden
will continue to decrease. A sponsor of a study subject to the
requirements of section 113 of the Modernization Act will have the
option of submitting data under that section or certifying to the
Secretary that disclosure of information for a specific protocol would
substantially interfere with the timely enrollment of subjects in the
clinical investigation. FDA has no means to accurately predict the proportion of protocols subject to the
requirements of section 113 of the Modernization Act that will be subject to a certification submission. To date, no certifications have been received. It is anticipated that the burden associated with such certification will be comparable to that associated with submission of data regarding a protocol. Therefore, the overall burden is anticipated to be the same, regardless of whether the sponsor chooses data submission or certification for nonsubmission. Table 1 reflects the estimate of this total burden.
In the Federal Register of August 25, 2003 (68 FR 51020), FDA published a 60day notice requesting public comment on the information collection provisions. No comments were received. Some of the estimates in table 1 of this document have been changed due to a miscalculation in the 60day notice. The total burden, however, remains unchanged. Table 1.Estimated Annual Reporting Burden\1\ Recruitment Protocol New Total Hours per New Protocols Complete Changes Investigators Site Closed Responses Response Total Hours CDER (mandatory); 1,319 1,319 1,568 3,108 3,108 10,422 4.6 47,941 CBER (mandatory); 304 304 543 585 585 2,321 4.6 10,677 CDER (voluntary); 2,638 2,638 3,182 6,311 6,311 21,080 4.6 96,968 CBER (voluntary); 606 606 1,103 1,188 1,188 4,691 4.6 21,579 Total 4,867 .............. .............. .............. 38,514 ............ 177,165 \1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
We believe the estimate, 177,165 hours per year (38,514 responses x
4.6 hours per response) accurately reflects the burden. We recognize
that companies who are less familiar with the data entry system and the
Clinical Trials Data Bank will require greater than 4.6 hours per
response. However, as sponsor familiarity with the system increases, the hourly estimate will decrease.
Dated: February 10, 2004.
Assistant Commissioner for Policy.
[FR Doc. 043488 Filed 21804; 8:45 am]
BILLING CODE 416001S
FOR FURTHER INFORMATION CONTACT
JonnaLynn P. Capezzuto, Office of Management Programs (HFA250), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 3018274659.