1. S1316 – The Malignant Bowel Obstruction Study Forms and Procedures
Katie Arnold, MS
SWOG Statistical Center
Seattle, WA
I will be referring to documents from the packet for this presentation. Please take a moment to find it. Many of the documents in the handout have their own page numbers. I will refer to the numbers in the upper right corner of each page, the “Packet Page” number.
10/24/2014
S1316 Training

2. S1316 Presentation Outline
Study timeline
Study flow
Eligibility and equipoise
Randomization (or not)
Endpoint and hospitalizations
Documenting MBO Treatment
Active vs. passive follow-up
I will be presenting the study timeline and study flow, touching on the important study concepts of equipoise, randomization and the two types of follow-up expected, and review a few key forms.
10/24/2014
S1316 Training

3. S1316 General Study Timeline
Patient hospitalized with MBO
Registration and randomization
Patient discharged from hospital
Weeks 1 – 13: Weekly calls from site
Weeks 17 – 53: Calls every 4 weeks from site
Study participation complete
This study has 6 important events and periods, starting with hospitalization for MBO and ending with study completion one year later.
On page 2 of your handouts is the S1316 Study Flow, a detailed description of each of these events and periods, derived from Sections 7, 9 and 14 of the protocol. I will refer to this during the first part of my presentation. The first column has the event or study period of interest, the middle column describes the activities that should occur during that time, and the last column lists the relevant forms and source documents that apply to each of those activities.
A copy of Section 9, the study calendar, is on page 5 of the handouts for your reference.
10/24/2014
S1316 Training

4. Patient Hospitalized with MBO
Eligibility
Equipoise
Informed consent
Patient chooses treatment assignment
Randomization (surgery vs. not)
Non-randomization (surgery only)
Looking at the first event on the Study Flow, a potentially eligible patient is hospitalized with MBO. As with any study, you need to establish eligibility and obtain informed consent.
Two critical features of S1316 are equipoise, specifically the notion that both surgery and non-surgical management of the patient’s MBO are appropriate treatments, and how treatment is assigned.
Equipoise is part of the eligibility criteria.
Treatment assignment for eligible patients can be established either by randomization or by patient choice.
Once patient registration and treatment assignment are complete (either randomization or patient choice), the follow-up is identical for each arm. Indeed, follow-up must e the same: same schedule, same forms, etc.
10/24/2014
S1316 Training

5. S1316 Registration and Randomization
Register
Randomize (if patient selected randomization)
Complete patient contact form for site
Complete and patient contact form for dietary recalls
Obtain baseline documentations
Administer baseline PRO forms
The second event on the Study Flow is Registration. A lot happens at this stage.
The patient is registered and his or her treatment assignment choice is recorded in OPEN. If the patient chose randomization, the randomization will be done via OPEN.
Because nearly all patient contacts are done via telephone, it is very important to obtain good contact information for the patients.
Pages 6 through 9 contain the two contact forms, one for use by the site for the weekly phone calls and the second for use by the Arizona Diet, Behavior and Quality of Life Assessment Lab, so they can administer the dietary recalls. The Dietary Recall contact form should be ed to the Arizona Lab within 24 hours, so the patient’s first recall at Week 1 will be timely.
And of course there are the Patient Reported Outcomes (PRO) forms and baseline data collection, as shown on the Study Flow.
10/24/2014
S1316 Training

6. S1316 Patient Discharged from Hospital
Collect MBO treatment data
Collect hospitalization documentation
Submit forms
So, the study clock starts ticking the day the patient is registered. Depending on the care the patient needs, he or she may still be in the hospital when the first weekly assessment rolls around. That assessment needs to be done whether or not the patient is hospitalized, and I will discuss the weekly assessment in my next slide.
Here, however, I want to cover what happens when the patient is discharged. This is the third event on the Study Flow.
The data for documenting the MBO treatment patients had during hospitalization is covered by the three forms listed on the Study Flow. I will describe them later.
The source documentation for hospitalization start and end dates is the discharge summary. These are needed for documenting the primary endpoint.
10/24/2014
S1316 Training

7. S1316 Weeks 1 - 13 Call patient weekly Obtain vital status
Administer PRO forms
Determine if patient spent any days in the hospital
If patient was hospitalized, obtain hospitalization and MBO treatment data
Submit forms
Dietary recalls every 4 weeks
The first 13 weeks are the most intense, as you can see from the next four events listed in the Study Flow.
Patients are contacted weekly by site staff to administer the PRO forms and find out about any hospitalizations.
If a patient was hospitalized, documentation of that hospitalization, including MBO treatment and discharge summary will be obtained.
Note that the dietary recalls are administered by the Arizona Diet, Behavior and QOL Assessment Lab.
In your packet, page 10, is the S1316 MBO Assessment Form. This is what you will use to record your weekly contact with the patient.
10/24/2014
S1316 Training

8. S1316 - Week 13 Report endpoint data
Determine which days patient was in the hospital during first 91 days after registration
Use discharge summaries and information from the weekly calls as source docs
Submit S1316 Hospitalization Days Document
At the end of the first 13 weeks, labeled as “Week 13” on the Study Flow, the data for the primary study outcome are reported.
All the discharge summaries and information about days out of the hospital collected during those weekly calls will need to be transcribed and submitted on the S1316 Hospitalization Days Record.
I will discuss this form later.
10/24/2014
S1316 Training

9. S1316 - Weeks 17 - 53 Call patient every 4 weeks Obtain vital status
Administer PRO forms
Determine if patient spent any days in the hospital
Submit forms
Dietary recalls every 4 weeks
As shown on the Study Flow, the data collection for the last 3/4 of the study, weeks 17-53, is greatly reduced. Site calls to patients are only every 4 weeks and the there is no requirement for detailed information on hospitalizations.
10/24/2014
S1316 Training

10. S1316 Study Participation Complete
Submit S1316 Off Protocol Notice
Participation is complete when a patient:
Completes 53 weeks of follow-up
Dies
Patient no longer wishes to receive phone calls but is willing to allow passive follow-up
The last three events shown on the Study Flow mark the end of a patient’s active participation in the study and require the submission of the S1316 Off Protocol Notice. I will discuss active and passive follow up later.
If, for any reason, the patient no longer wants to receive the weekly calls from the site and the Arizona Lab, the Off Protocol Notice should be submitted to place the patient on passive follow-up. This will trigger a report to the Arizona Lab so they know not to call the patient. Please submit the Off Protocol Notice as soon as you can, so the Arizona Lab receives that information in a timely manner.
This concludes my overview of the study flow.
10/24/2014
S1316 Training

11. S1316 Eligibility and Equipoise
Clinicians must have equipoise for a patient to be eligible.
That means the patient’s MBO can reasonably be treated via surgery or non-surgical medical management.
Surgery Non-surgical management
Now I’d like to go into more depth on a few topics I touched on earlier, starting with equipoise.
Please take a look at page 11 of your handout, which is Section 5 of the protocol, the eligibility criteria. Section 5.1c, d and e address equipoise.
Clinicians must demonstrate equipoise for the benefit of surgery to correct a potentially eligible patient’s MBO symptoms. In other words, the patient’s MBO can reasonably be treated via surgery or non-surgical medical management. This does not mean that the patient or physician cannot have a strong opinion about how he or she wants to proceed. Indeed, it is unlikely that anyone won’t have an opinion!
Documentation of the surgical team’s statement of equipoise is recorded on the S1316 Surgical Equipoise Documentation, which is on page 13 of your handouts.
Equipoise is especially important because the study has both a randomized and a non-randomized components. The possibility for bias will be less if the physicians have equipoise.
10/24/2014
S1316 Training

12. S1316 Randomization (or not)
Meets all
eligibility
requirements (N=200)
Consents to randomization
(N=34)
Consents to non-randomized treatment
(N=166)
Surgery (50%) (Arm 1)
Non-surgical management (50%) (Arm 2)*
Surgery (Arm 3)
Non-surgical management (Arm 4)*
Primary Outcome: “Good days” = days out of the hospital and alive in the first 91 days (13 weeks) after registration
*Recommend a trial of somatostatin analog
Now a few words about treatment assignment and randomization.
This is our schema, which you saw earlier from the professional slide set. As Dr. Anderson discussed, all eligible patients should be asked first if they are willing to be randomized to MBO treatment. If they are unwilling, then they may specify which treatment they prefer and still participate in the study.
The patient’s treatment assignment (randomization, surgery or non-surgical management) is recorded on the S1316 Registration Worksheet, found on page 14 of your handouts.
The worksheet will be used to complete the patient’s registration in OPEN.
Under “Stratification Questions” is a place to mark the primary tumor type and below that, the patient’s chosen treatment assignment.
If the patient chooses randomization, OPEN will randomize the patient and provide his or her actual treatment assignment.
10/24/2014
S1316 Training

13. S1316 Endpoint and Hospitalizations
S1316 Protocol Section 1.1 Primary Objective To compare quality of life, as assessed by the number of days alive and outside of the hospital within the first 91 days (13 weeks) after registration, among patients with malignant bowel obstruction (MBO) who receive surgical intervention and similar patients treated non-surgically.
Moving on to the study endpoint…
The primary outcome for this study is the number of days alive and outside the hospital during the patient’s first 13 weeks on study.
An accurate accounting of the patient’s status for each of these days requires the we know where he or she was each day.
This led to the S1316 Hospitalization Days Record, found on page 15 of your handouts.
This was designed to be like a calendar, showing the first 13 weeks after registration, with a place to mark the hospitalization status of each day.
This form will be completed and submitted after the first 13 weeks, based on the discharge summaries collected and the information gleaned from weekly patient interviews.
For each day, starting with the day the patient was registered at the initial hospitalization, record the patient’s hospitalization status.
Mark “Yes” if the patient spent any part of it hospitalized.
Mark “No” if the entire day was spent out of the hospital.
Mark “Unknown” if you do not know the patient’s status for that day.
Finally, mark “N/A” if the day is before registration or after the patient’s death.
This will be available to you as a template online.
Note that the form in Rave looks very much like this one, except the dates along the left side will be populated for you.
The Rave form will default to “N/A” for each day.
This is the data collection form for the study endpoint, so I want to be sure this is clear.
Any questions at this time?
10/24/2014
S1316 Training

14. S1316 Obtaining Complete Endpoint Data
Need hospitalization status for each day
Leverage the weekly calls to cover any missed periods
Protocol Section 7.5b
So, that is where and how to record the endpoint data. But what if you can’t complete the contact with the patient for a week or maybe several weeks?
It is our hope and expectation that when a weekly contact is missed, the next completed contact will cover the entire period between completed contacts. This is stated in Protocol Section 7.5b, on page 18 of your packet.
Missing endpoint data for this study will be informative, meaning that patients who are missing endpoint data are likely to be different than patients who have complete endpoint data. We can’t use fancy statistics to deal with missing data on a large scale. Please help keep missing data to a minimum.
10/24/2014
S1316 Training

15. Documenting MBO Treatment
3 paper forms to document MBO treatments
S1316 MBO Treatment Form
S1316 MBO Treatment Complications Form
S1316 Somatostatin Analogue Treatment Form
Surgery
Non-surgical
Home care
During the patient’s first 13 weeks on the study, we will collect extensive information about any and all hospitalizations, including the initial hospitalization and hospitalizations not related to MBO.
The three forms used to collect these data are listed on the slide; the first, the MBO Treatment Form, is shown starting on page 19 of your handouts.
Briefly, the S1316 MBO Treatment Form collects all MBO treatment received by the patient at that hospitalization, both surgical and non-surgical. Please note the dates you enter on this form will be perpetuated to the other two forms, for consistency (and less typing for you). This form also collects any discharge medications and home care prescribed. Submit this form even if the patient was hospitalized for a reason other than MBO or did not receive any MBO treatment.
The S1316 MBO Treatment Complications Form is similar to the usual SWOG tox form. We really only want complications related to MBO treatment reported. Complications solely attributable to the patient’s cancer or MBO disease should not be recorded here.
Finally, any somatostatin analogue treatment received will be reported on the S1316 Somatostatin Analogue Treatment Form. This is a daily log of the total somatostatin analogue received by the patient while hospitalized.
Note that a discharge summary is needed for any and all hospitalizations during the first 13 weeks on study, for endpoint documentation.
10/24/2014
S1316 Training

16. S1316 Active vs. Passive Follow-Up
Active follow-up
Patient allows phone calls and all study activities
Passive follow-up
Patient allows all study activities except phone calls
Submit S1316 Protocol Notice ASAP to stop dietary recall contacts
No follow-up
Patient does not want any further follow-up of any kind
Request SWOG Consent Withdrawal Form from Data Coordinator
The follow-up for S1316 is done entirely by telephone, so the demarcation between active and passive follow-up is very important.
The three levels of follow-up are listed here.
All patients are on active follow-up when they register.
We anticipate that some patients may decide along the way that they just don’t want to receive any more phone calls, either from the site staff or the Arizona Lab (dietary recalls). These patients will be placed on passive follow-up, through submission of the S1316 Off Protocol Notice. Note that the dietary recalls will stop only after the Off Protocol Notice has been submitted, so please don’t delay submission of this form.
All forms are expected to be submitted for patients on active and passive follow-up, including weekly assessment forms (for vital status) and forms relating to known hospitalizations. For patients on passive follow-up, the data will have to come from the patient’s chart. Gather as much data as you can for these patients.
If a patient refuses any further follow-up or contact, please follow SWOG policy.
10/24/2014
S1316 Training

17. S1316 Forms and Documents Overview
Form or Document Name
Primary Purpose
When collected
How collected
When submitted
The last few pages of your packet are an overview of the S1316 forms and documents needed for this study.
The information here was gleaned from the protocol Sections 7 and 14.
The first column lists the form or document. The next column describes the purpose of that form or document. The next three columns describe when the data are collected, how the data are collected, and when the data should be submitted.
It will be available as an Excel spreadsheet online as a resource for you. Please note this does not replace or supersede the protocol.
10/24/2014
S1316 Training