Guidance on Presenting Changes of Protocol to IRB
Version Date: November 29, 2011
Effectively communicate to the IRB what will be changed, why the changes are being proposed, how the revisions alter the IRB-approved protocol, and the impact of the changes on the risk/benefit ratio of the study will reduce modification requests from the IRB and shorten IRB review time. This document was prepared to help study teams present clear and complete descriptions of changes of protocol.
Change Form vs. Modified IRB Application
In ARROW study teams must complete 2 steps when preparing a change of protocol.
Step 1: The first step in completing the change form, which is where study teams identify and describe the proposed changes. Do NOT upload any revised study team documents (e.g., consent document, protocol) to the change form. For guidance on completing the change form, please see the "How to Describe Changes" section below.
Step 2: The second step is revising the modified application. The modified application is a copy of the currently approved IRB application for a study. The modified application must be revised to reflect the proposed changes described in the change form, including uploading any documents that are being revised as part of the change of protocol. These changes need to be reflected in the IRB application because this document is used by the IRB to track changes to the study over time. It is important for study teams to consider all the areas of the application that may be affected by a specific change. For example, a change in sample size affects the Subject Population pages of the application and requires updates to the protocol document and consent forms; if the increase in sample size includes a new subject group it will also affect the Research Design sections of the application and protocol, and may affect recruitment procedures and recruitment materials. Neglecting to consider the "ripple effect" of a revision makes IRB pre-review more time-consuming.
For additional guidance on this 2 step process, please see How to Complete Changes of Protocol .
Providing Documents with Changes Tracked/Highlighted
In order for an IRB to assess updates to previously documents, study teams must upload copies of any study documents to which changes are being made. For example, if a formal protocol is associated with the study and is being updated, the revised version of this document must be upload into ARROW. The changes made to documents must be highlighted or tracked so that the IRB can easily compare the previous version of a study document with the revised version. The tracked changes function in Microsoft Word is the preferred way of highlighting revisions to documents. All revised documents should be uploaded using the Upload Revisions button in the modified application.
How to Describe Changes
The change form asks study teams to provide a description of each change, a rationale for the proposed changes, and describe what effect, if any, each change will have on the risk/benefit ratio of the study. Specific guidance regarding how to address each of these sections as follows.
- Description of each of the proposed changes.
It is essential to explain why changes are being made. In some cases, there is an overall rationale for the changes (e.g., recruitment has been slow and the sample size, eligibility criteria, and recruitment methods are being revised in an effort to increase the accrual rate and enable the study to be completed in a reasonable time period). In other cases, each specific revision is being made for a different reason that should be described.
- Description of what effect, if any, each change will have on the risk/benefit ratio of the study.
This section should also address any changes in design or sample size that would affect whether the study’s objectives can still be met. If substantive changes in study design are being made, please provide a new statistical justification, describe how data collected before this change will be incorporated into analyses, and address why the study should continue.
- Effect on Informed Consent Process and Documents
- Description of revised documents
Examples for the presentation of a change of protocol
Example #1Change in study visits: We wish expand visit window for resolution visits to accommodate the occasional subjects who do not resolve their cold symptoms within 6 weeks of the acute infection they undergo for this protocol.
Description of Changes Section
Change in experimental gas dosing: We propose to broaden the options for use of a third dose of an experimental contrast gas for MRI imaging (Visit 2 and 9).
Rationale for change in experimental gas dosing: The technology and hardware used to acquire the MR images is relatively new, and there have been instances when unanticipated failures have led to lost data. When this happens, the researchers would like the option to use a third dose of the experimental contrast gas rather than repeat a scan. The faster imaging will allow a shorter breath hold time and has been previously tested on normal volunteers. It is necessary to validate the newer technique in patients with lung disease so that it can be compared to existing imaging sequences. The use of the third dose of the experimental contrast gas will extend the total exam time by 10 minutes (see revised consent form) to allow for additional preparation time of the gas and scanning.
Rationale for change in study visits: There are individuals who do not resolve their cold symptoms within 6 weeks of an acute respiratory infection. We would like to obtain resolution assessments at a time when cold symptoms have resolved so that these assessments can be used as a baseline for the acute cold assessments.
Effect of Risk/Benefit Ratio Section
Effect of change in experimental gas dosing on risk/benefit ratio:
The proposed change should have no effect on the risk/benefit ratio. Previous protocols at this site (IRB number 2010-XXX, 2011-XXX) and at other sites have used three doses of the experimental contrast gas in smoking and non-smoking subjects, and in patients with a wide range of diseases, including asthma, chronic obstructive pulmonary disease, and cystic fibrosis without serious adverse events and no respiratory-related adverse events. The risk due to the use of the experimental gas already exists in the current protocol and is addressed by continuous monitoring of ECGs and blood oxygen saturation. There is no increased risk to subjects associated with the additional inhalation of the gas assuming adequate recovery of between breath holds; the current 5-10 minute gap between scans to prepare each dose of the gas should provide adequate recovery time. We have scanned more than 60 subjects for this present protocol with no respiratory-related adverse events. The procedure description has been modified in the protocol to include the option third dose of the gas.
Effect of risk/benefit ratio: No effect expected to risks to subjects. The change may increase scheduling inconvenience. The protocol and consent form have been revised to include the potential need to delay the resolution study visit.
Revised Document Section
The following documents have been revised to reflect these changes and uploaded in the initial review application: the study protocol (to reflect the additional dose of experimental contrast gas and change in window for resolution visits), Main Study Consent Form for Healthy Volunteers, (to reflect the addition of the dose of the experimental contrast gas and potential need to delay the resolution study visit) and letter to potential subjects (to reflect the addition of the dose of the experimental contrast gas).
Description of Changes Section
Change to survey instrument: We would like to ask participants what they believe the directions for each inhaler is during the final interview. It will be phrased as "What are the directions for ____ inhaler" and will be asked for each inhaler. We will be looking for number of puffs taken and number of times daily taken.
Addition of a new study site: Because recruitment is occurring at a lower rate than expected, we are proposing to expand recruitment of subjects to include patients at UW Health Clinic West. The same subject identification and consent procedures will be followed as previously described, but additional study team members are being added who will obtain informed consent and perform study procedures at that clinic. A separate personnel change form will be submitted to add the new personnel. A letter of support for this study from the clinic manager has been uploaded in the IRB application and the protocol has been updated to reflect the new site.
Addition of a new federal grant: The PI received funding from NIH for this study, which is being added to this protocol. This study was previously unfunded.
Rationale for change to survey instrument: Recently, while reviewing data from the counseling session there were quite a few participants who were unable to report correct inhaler directions. We spent some time educating on inhaler directions and would like to see if there is a difference in understanding of inhaler directions between the two groups
Rationale for new study site: Opening recruitment at UW Health Clinic West should increase the chances of meeting our original recruitment goals. We expect to be able to recruit 10-15 subjects from this site.
Rationale for adding the new federal grant: Aim 1 of the federal grant describes the activities that will occur in this pilot study. Aims 2 and 3 will be submitted as a separate IRB protocol.
Effect on Risk/Benefit Ratio Section
Effect of change to survey instrument on risk/benefit ratio: The addition of inhaler directions should not change the risk/benefit ratio. If a participant does not want to answer the question for any reason they can choose not to answer. Additionally, if a participant does report incorrect inhaler directions, the interviewer can review correct inhaler directions with the participant and they may begin to use their inhalers correctly
Effect of new study site on risk/benefit ratio: The addition of the study site should not affect the risk/benefit ratio as the same privacy and confidentiality protections described for the original subject population remain in place and the new location’s facilities are commensurate with the clinic the IRB already approved.
Revised Document Section
The following documents have been revised to reflect these changes and uploaded in the initial review form: the study protocol (revised to add the new sites and clarify recruitment procedures followed at each site), main survey instrument (to reflect the change in question about inhaler directions described in this change), and several recruitment materials - subject brochure, letter to subjects, study flyer, newspaper advertisement – (to reflect the additional recruitment sites). In addition to the revised document, a copy of the federal grant that now supports this study has been uploaded in the initial review form.