Change Request Memo

UNITED STATES FOOD AND DRUG ADMINISTRATION

FDA Adverse Event and Products Experience Reports; Electronic Submissions

OMB Control Number 0910-0645

Non-Substantive Change Request for CTP Safety Reporting Portal Questionnaire

FDA’s Center for Tobacco Products (CTP) requests OMB approval of this change request under 0910-0645. The ICR package represents a non-substantive change to CTP’s Safety Reporting Portal (SRP) tobacco RQs (i.e., “Rational Questionnaires”: “TPR¹” or “Tobacco Product Report” and “TIR”² or “Tobacco Investigator Report”).

Specific Aims of Updates to the Questionnaires Proposed to Launch in 2020:

• Identify duplicate reports to more than one entity by converting an existing optional question with free-text response to “Did you report this problem elsewhere?” if yes, asks where else the problem was reported with 9 options (select all that apply) (TPR & TIR).

• Conditionally require reporting the number of affected users or nonusers when a health problem is reported (TPR & TIR)

• Capture the age of the affected person (previously optional, now required in TPR & TIR) due to the youth epidemic of tobacco product initiation. Two age units are added; unknown adult (age 18 years or older and unknown minor (under age 18 years) (TPR & TIR).

• The requirement to report age is offset by deleting the optional question on Date of Birth.

• Optionally ask the body weight to align with MedWatch and to assist understanding of potential nicotine toxicities (TPR & TIR)

• Identify vulnerable populations affected, to comply with the minimum OMB disability data standard ( https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=3&lvlid=53 ) as well as the general layout of the SRP questionnaire (adds one new questions on English language mastery in TPR in the Contact Information section and one revised question on specific pre-existing disabilities in TPR & TIR in the Problem Summary section)

• Move the location of one existing question about temporal association of the problem to the tobacco product use, to address order effects observed for all tobacco product types in both RQs.

• Capture better identifying information for ENDS (“e-cigarettes”) in both RQs, their operating modes, post-market modifications and their companion e-liquid sources and contents to assist understanding of failure modes and potential contributors to reported health effects. There were previously 16 questions that touched on identifiers for the electronic device or the companion e-liquid. We propose now to host 21 device identifier questions (7 are unchanged, 2 are modified) and 15 e-liquid identifier questions.

• The additional ENDS questions are offset by the deletion of 35 questions (from both RQs) about tobacco product parts, which have been replaced by a single question asking for a free-text identification of involved tobacco product parts.

• Convert three existing optional questions to required questions in the TIR: Seriousness, expectedness and relatedness of the event to the investigational tobacco product. The expectedness question is relocated and reworded to avoid a double negative in the response. The seriousness and relatedness question stems are reworded to make it clear that the responses should be from the Principal Investigator. The relatedness question is also relocated.

• Add optional questions to the “Tobacco Product Use Details” for all tobacco product types:

  • How long has the affected person been using this type of tobacco product? (exists in TPRv3, now adding to TIR) to understand potential effects of switching product types

  • How long has the affected person been using any type of tobacco product? (both RQs) to understand effects in initiators vs established users

  • “Did the affected person follow the instructions for product use?” to assess human factors contributions to the reported AE (TPR)

• Provide an “unknown” and/or “other” option (with a free-text ability to explain a choice of “other”), as appropriate, to most existing and new multiple choice lists of response values in both RQs since many reports are submitted by parents and other concerned citizens who may not have all desirable details about the affected person (TPR) and to accommodate research reporters who may have an incomplete set of information on subjects who are lost to follow-up (TIR)

• Pilot a mobile-friendly subset of the TPR questions for guest (not account-holding) submitters to begin to accommodate the growing migration from desktop to mobile device use and to inform future RQ revisions. (One unique required question asks if the submitter wants the full (not mobile formatted) or the subset TPR (mobile formatted) RQ.) In the mobile formatted TPR guest RQ, nearly all contact information and problem summary questions are presented, with few product identifier questions, the optional additional information type-in field, and at least one attachment is required that we hope will be a product image (vs. being optional in the full RQ – although the system will accept an image of anything which may or may not be the desired product image). Note that it has always been possible to submit full reports on mobile devices, but to do so remains unwieldy because screens in the desktop platforms are not formatted for mobile devices.

Added or Revised Response Values to Existing Questions (not mentioned elsewhere):

• Existing required question (in both RQs) “Who was affected by this tobacco problem?” adds values of “Neither” and “Unknown” which displays to those who report a product problem only

• Add one response value to the seriousness question in the TPR Problem Summary section, “Other serious/important medical event” to align with MedWatch and to allow an appropriate seriousness designation for problems that require workup and monitoring but may not require admission or treatment initially (such as new onset of seizure)

• Update labels to four Tobacco Product types (ENDS, Heated tobacco products, Waterpipe and Cigar) and an updated E-cigarette subtype list of values to reflect shifts in the consumer vernacular and increased scientific product knowledge. These lists are shown identically in two places in each RQ for internal consistency.

• The existing optional question, “How was the tobacco product used?” adds 1 new and 2 revised response values for a new total of nine choices compared to the previous seven choices. (for all tobacco product types in both RQs)

• The existing optional question, “How was this product acquired?” (TPR only for all tobacco product types) has three new response values and two revised values for a new total of eight values compared to the previous six

• For the existing and new questions on tobacco product contents, when any product in either RQ is said to contain flavor(s) the multiple-choice list of flavors has been expanded from 9 choices to 18 choices to reflect research on this topic and consistent with CTP’s ENDS enforcement priorities recently in effect

• When the value “other” is selected to an existing required question, the free-text field for explaining “other” is also required

  • Conditionally requires two free-text explanations if the DSMB and IRB were not notified of the event for an “other” reason in the TIR

  • Conditionally adds two required questions to both RQs to explain the “other” product problem if applicable and to explain the “Other” tobacco product type when applicable.

Deleted Questions and Response Values Specifically Decreasing Public Burden (in addition to deletions mentioned above):

• Removing the optional question: “Where is the tobacco product now?” for all tobacco product types in the TPR and its counterpart “Does the investigator still have access to the study product?” in the TIR

• Removing the question asking for a free-text explanation of the dates/times of study tobacco product administration relative to the problem in the TIR

• Deleting the MedDRA lower level term “other” from the list of available terms from both RQs

• Tobacco Product Use Details Section deletions for all tobacco product types in both RQs

  • “Describe what substances are being mixed in with the tobacco product” for all tobacco product types in both RQs.

  • “Did the problem occur with first time use of the study tobacco product” for all tobacco product types in the TIR.

Functional Enhancements to Both RQs to Facilitate the Submitter’s Experience:

• Improved instructional and informational content in both RQs

• The existing optional question on manufacturer name (Tobacco Products in TPR or Study Tobacco Products in TIR sections) now has response values selectable from CTP’s registration and listing manufacturer’s database (this will show both active and inactive manufacturers) to facilitate easy and accurate selection

• The existing optional question on UL certification for electronic tobacco product types now shows an image of the UL symbol to educate and assist recognition (TPR & TIR)

• The existing linked document (for optional viewing) illustrating and defining tobacco product types, bears updated images and descriptors (TPR & TIR) (See the enclosed “Product Type Images Desc for TPRv4_TIRv3 marked up.docx”).

• Researchers have the ability to designate the version of MedDRA terms they use to accommodate the typical practice of version freezing for long-term studies (TIR)

• A new character count-down tool alerts the user to how many characters a free-text field can accept and when they are nearing the limit, to decrease error message experiences (TPR & TIR)

Numbers of Required Questions within the Voluntary Reports to Each RQ:

• Four questions continue to be required at the SRP level to navigate to the correct RQ out of the ~ 10 RQs hosted by FDA and NIH– this is outside of CTP’s direct control.

• A health problem report can be submitted by answering as few as nine questions inside the TPR for most tobacco product types.

• A report of both a health and a product problem for the ENDS tobacco product type, can be submitted by answering as few as 13 questions inside the TPR (three are new).

• To submit a report to the TIR, eight research-specific questions are required (three are new) in addition to the 9 or 13 from the above TPR examples (for totals of 17 or 21).

List of documents	Description
CTP SRP TPRv3 marked up.pdf	Screen prints of the 12/15/2018 release (“TPRv3”) of 0645 with markups to show the planned changes for release in 2020 (“TPRv4”) (shows the existing questions for all non-ENDS tobacco product types)
CTP SRP Proxy TIRv2 marked up.pdf	Screen prints of the 12/15/2018 release (“TIRv2”) of 0645 with markups to show the planned changes for release in 2020 (“TIRv3”) (shows the existing questions for all non-ENDS tobacco product types)
Revised ENDS Qs for TPRv4 and TIRv3.pdf	The existing, revised and new questions on the tobacco product type, E-cigarettes… to be used in TPRv4 and TIRv3 proposed for release in 2020
Product Type Images Desc for TPRv4_TIRv3.docx	Exact instructional text and images document proposed to be posted to >https://www.safetyreporting.hhs.gov/srp2/CTP/TobaccoProductsParts.html< with TPRv4 and TIRv3 in 2020
TPR Mobile Screenshots 4-16-2020.pdf	Screen captures of the mobile formatted subset of the TPRv4 for guest reporters, for first release in 2020

The live 2018 versions of both RQs (TPR and TIR) can be accessed at https://www.safetyreporting.hhs.gov .

1 The TPR continues to be designed for consumers/concerned citizens (as anonymous guests or identified account holders), healthcare professionals (as anonymous guests or identified account holders) and manufacturers (as identified account holders). The 2018 version currently in the field is “TPRv3”. The proposed 2020 version is “TPRv4”.

2 The TIR continues to be designed for researchers (as identified account holders). The 2018 version currently in the field is “TIRv2”. The proposed 2020 version is “TIRv3”.