Supporting Statement for

Guidance on Informed Consent for *In Vitro* Diagnostic Device Studies
Using Leftover Human Specimens that Are Not Individually Identifiable

Docket #2005N-0507

Expires 09/30/06

## **A. JUSTIFICATION**

1.  **Circumstances Necessitating Information Collection**

> **\
> **The Food and Drug Administration has developed a guidance document
> that addresses an immediate need of the research community. The
> guidance will identify circumstances when the agency intends to
> exercise enforcement discretion regarding informed consent
> requirements. FDA intends to apply enforcement discretion to studies
> of *in vitro* diagnostic devices that are conducted using leftover
> specimens \-- remnants of specimens collected for routine clinical
> purposes that would otherwise have been discarded \--and that meet the
> criteria for exemption from the Investigational Device Exemption (IDE)
> regulation at 21 CFR 812.2(c) (3), as long as subject privacy is
> protected by using only specimens that are not individually
> identifiable. (Attachment A) This exercise of enforcement discretion
> regards the requirements for informed consent that normally apply to
> all FDA-regulated clinical studies (as required by section 520(g) of
> the Federal Food, Drug, and Cosmetic Act and 21 CFR part
> 50). (Attachment B) The agency developed this guidance because the
> existing requirements are bringing a halt to a class of very valuable
> research that can produce new diagnostic tests. FDA believes these
> requirements do not, in the circumstances described above, appreciably
> add protection for human subjects, which is the purpose of having
> informed consent requirements in the first place.
>
> The agency has received information that numerous studies have been
> rejected because of the existing rules.  These new products have
> potential to improve the public health by providing new tools for
> diagnosing many diseases or conditions, some of which may at present
> have no established means of lab diagnosis. Without this policy,
> valuable research is at best slowed considerably by the need to gather
> a prospective group of subjects (as opposed to using leftover
> materials already at hand) and at worse may become prohibitively
> expensive and not undertaken.  This is contrary to the agency\'s
> mission, and to its commitment to removing unnecessary obstacles to
> product development.  In addition to the impact on the development of
> new diagnostic devices, this requirement also has a negative impact on
> development of new drugs and biological products, many of which rely
> on the results of diagnostic tests to identify the patients for whom
> they are suitable.
>
> FDA will notify the public, in a level one guidance document issued
> pursuant to the Good Guidances Practices regulation, 21 CFR 10.115, of
> the circumstances in which it intends to exercise enforcement
> discretion as to the informed consent regulations for clinical
> investigators, sponsors, and institutional review boards (IRBs).
> (Attachment C) In the guidance document, FDA recommends that sponsors
> of studies that meet the factors maintain documentation of how these
> factors were met and of the types of human subject protection
> procedures followed by the specimen provider to ensure that the
> subject cannot be identified.

2.  **How, by Whom, Purpose of Collection**

> After receiving OMB clearance under the Paperwork Reduction Act (PRA),
> FDA will announce the availability of a guidance entitled, "Guidance
> on Informed Consent for *In Vitro* Diagnostic Device Studies Using
> Leftover Human Specimens that are Not Individually Identifiable." The
> guidance defines when the agency intends to exercise enforcement
> discretion regarding informed consent requirements (21 CFR parts 812,
> 50) with regard to leftover human specimens that are not individually
> identifiable that are used in certain *in vitro* diagnostic studies.
> (Attachments D, B and E)
>
> The guidance document recommends that sponsors that meet the factors
> described in the guidance maintain records of how these factors were
> met. Sponsors that wish to take advantage of this policy will
> substitute use of records to demonstrate conformance to this
> enforcement discretion policy in place of the more detailed and
> patient specific records for obtaining and document informed consent.
> Most fundamentally, this means collecting and maintaining information
> about the protections that are in place to prevent the identification
> of the specimens, since making sure that the specimens are not
> identifiable is key to obtaining FDA\'s enforcement discretion.
>
> FDA intends to exercise enforcement discretion when all the following
> are true:

-   the investigation meets the IDE exemption criteria at 21 CFR
    812.2(c)(3), (Attachment A);

-   the study uses leftover specimens, that is, remnants of specimens
    collected for routine clinical care or analysis that would have been
    discarded. The study may also use specimens obtained from specimen
    repositories or leftover specimens that were previously collected
    for other research purpose may also be used;

-   the specimens are not individually identifiable;

-   the specimens may be accompanied by clinical information as long as
    this information does not make the specimen source identifiable to
    the investigator or any other individual associated with the
    investigation, including the sponsor;

-   the individuals caring for the patients are different from and do
    not share information with those conducting the investigation;

-   the specimens are provided to the investigator(s) without
    identifiers and the supplier of the specimens has established
    policies and procedures to prevent the release of personal
    information; and

-   the study has been reviewed by an IRB in accordance with 21 CFR part
    56 (Attachment E).

3.  **Consideration Given to Information Technology[\
    \
    ]{.underline}**Companies are free to use whatever forms of
    information technology may best assist them in utilizing this
    guidance document.

4.  **Identification of Duplicative Information**

> As this is a guidance document, no firm is required by regulation to
> take advantage of this policy. There should be no duplicative
> information collection as a result of this guidance.

5.  **Small Businesses[\
    \
    ]{.underline}**This guidance document offers clinical investigators
    and sponsors a pathway for using leftover human specimens that are
    not individually identifiable. This will be an alternative to
    existing requirements for sponsors to obtain informed consent, which
    could be extraordinarily time-consuming and costly, if not
    impossible. This pathway is not currently available; thus the policy
    expressed in the guidance document should help facilitate important
    research in a cost-effective way.

6.  **Less Frequent Collection**\
    \
    This guidance may reduce the information collection burden on
    clinical investigators and sponsors by requesting only that they
    meet the factors in the guidance, rather than keeping the records
    and satisfying other information collection requirements related to
    obtaining informed consent. The clinical investigators and sponsors
    need to maintain written documentation demonstrating that they meet
    the factors in the guidance only if they choose to take advantage of
    the policy expressed in the guidance.

7.  **Special Circumstances**

> There are no special circumstances associated with this information
> collection.

#  **8. Federal Register Notice/Outside Consultation [ ]{.underline}**FDA received seven sets of comments in response to a January 9, 2006, Federal Register Notice (71 FR 1429) soliciting comments on the proposed collection of information. FDA has made revisions to the guidance in response to the comments, including clarifications on the factors such as the amount of clinical information that may accompany the specimens. The scope of the guidance has been expanded to include leftover specimens that were previously collected for other research purposes. Because expansion of the scope means that more studies might be able to follow this policy instead of the requirements of informed consent, FDA has increased the number of studies affected in the burden table below. 

# 

#  Other revisions to the guidance include a temporal qualifier related to leftover specimens and further clarification on what makes a specimen not individually identifiable. Several comments from the same institution requested the investigator to have access to a coded specimen identifier. These comments were not incorporated into the guidance because the premise of exercising enforcement discretion under this guidance is the inability of the investigator or any other individual associated with the investigation, including the sponsor, to identify the subject from whom the specimen was collected. This is to minimize concerns associated with privacy.

# 

# One of the comments requested FDA to clarify how the factors described in the guidance can be extended to other similar situations, under the assumption that IRBs will be pressured to apply this guidance beyond studies using leftover specimens. This guidance makes very clear that the intended enforcement discretion regarding informed consent requirements is limited to studies having all of these characteristics. 

> **9. Payment or Gift to Respondent**\
> \
> This information collection does not provide for payment or gifts to
> respondents.

10. **Confidentiality Provisions**\
    \
    This information collection will be used only to assist clinical
    investigators, sponsors, and IRBs in conducting research with
    leftover specimens that are not individually identifiable.

> **11. Sensitive Questions**\
> \
> This information collection does not include any questions of a
> sensitive nature.
>
> **12. Burden of Information Collection**
>
> FDA estimates the burden of the collection of information described as
> follows:
>
> Table 1. -- Estimated Annual Recordkeeping Burden^1^

  ------------------ ----------------- ------------ ---------- ------------------
  **No. of           **Annual          **Total      **Hours    **Total Hours**
  Record-keepers**   Frequency of      Annual       per        
                     Recordkeeping**   Records**    Record**   

  700                1                 700          4          2,800
  ------------------ ----------------- ------------ ---------- ------------------

1.  There are no capital costs or operating and maintenance costs
    associated with this collection of information.

> The recommendations of this guidance impose a minimal burden on
> industry. The FDA estimates that 700 studies will be affected
> annually. Each study will result in one recordkeeping per year,
> estimated to take 4 hours to complete. This results in a total
> recordkeeping burden of 2,800 hours. (700 x 4 = 2,800)
>
> FDA estimates that cost of developing standard operating procedures
> for each record keeper is \$300. (6 hours of work at \$50/Hr.) This
> results in a total cost to industry of \$210,000. (\$300 multiplied by
> 700 record keepers) FDA estimates that operating costs for collecting
> this information is \$300 per record keeper. (6 hours of work at
> \$50/Hr.) This results in a total operational and maintenance cost to
> industry of \$210,000. (\$300 multiplied by 700 record keepers) The
> total cost of this recordkeeping, capital plus operational and
> maintenance cost is estimated to be \$420,000.

13. **Capital Costs (Maintenance of Capital Costs)**

> There are no capital costs or operating and maintenance costs
> associated with this collection of information.

14. **Cost to Federal Government**\
    \
    There are no annualized costs to the Federal Government as a result
    of this guidance.

15. **Reason for Change**\
    \
    This is a new collection.

16. **Publication and Tabulation Dates**\
    [\
    ]{.underline}The agency has no plans for publication of information
    from this information collection.

17. **Display of OMB Approval Date**\
    \
    There are no reasons why display of the expiration date for OMB
    approval of the information collection would be inappropriate.

**Exceptions to "Certification for Paperwork Reduction Act
Submissions"**\
\
There are no exceptions to the certification statement identified in
item 19 of OMB Form 83-I.

**List of Attachments:**

1.  Attachment A: 21 CFR 812.2.

2.  Attachment B: 21 CFR part 50.

3.  Attachment C: 21 CFR 10.115.

4.  Attachment D: 21 CFR part 812.

5.  Attachment E: 21 CFR part 56.