Theradex SAE Reporting

Name: Theradex SAE Reporting
Uploaded: 2022-03-09T19:26:08.203Z
Duration: 52 min 48 s
Description: Presented by Cynthia Neydon on February 18, 2022 | Audience: CRN, CRC and CRA – open to other positions | Purpose: Reviewing the Theradex SAE reporting process with an auditor.

March 09, 2022

Presented by Cynthia Neydon on February 18, 2022 | Audience: CRN, CRC and CRA – open to other positions | Purpose: Reviewing the Theradex SAE reporting process with an auditor.

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ID: 7518
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00:03And.
00:07I it's it's 133,
00:08so let's go ahead and get started.
00:10I know it's a Friday afternoon and
00:12and Cynthia thank you again for
00:15giving us your time to review some
00:17of the essay reporting requirements.
00:19So I will hand it off to you
00:21and just note to anyone.
00:23If you have questions or
00:25comments or anything feel
00:26free to use the chat. I'll be
00:27checking it throughout the the
00:29discussion this afternoon.
00:33OK, well welcome everyone and.
00:38Again, I'm not. I'm not 100%
00:40exactly what you wanted to review
00:43in terms of adverse event reporting,
00:45but I will just go through a few things
00:48that I put together and then we can.
00:51You know, discuss it if you have any
00:53questions, I'm happy to answer any
00:55questions you may have and also.
00:57If you want me to go over the SAE reporting,
01:00like I said, I will be happy to pull
01:03that PowerPoint up and we can go
01:05through the new process for reporting
01:07SCE with the integrated studies. Uhm?
01:10But in general I just wanted to kind
01:13of go over at like the adverse events.
01:16So I think.
01:18You all probably understand all
01:20these definitions.
01:20You know,
01:21adverse event is really anything
01:23that was undesirable and unintended
01:26that is experienced by the patient.
01:28It doesn't matter if it's related
01:30to the study treatment,
01:32but it wasn't present at baseline,
01:33or if it was present it worsened
01:36or the attribution changed.
01:38Serious adverse events are ones that are.
01:42Result in one of the following
01:44their their death life threatening
01:46a hospitalization that's initial or
01:48prolonged and its hospitalization
01:49for an event.
01:50Not for like a an elective procedure.
01:53Disability or permanent damage
01:56congenital anomaly.
01:57Or birth defect in another
01:59serious important medical event.
02:00So the important medical event
02:02is the one where I think we get
02:04hung up a little bit.
02:05The NCI likes all Grade 3
02:09AE's to be assessed for,
02:11whether they're an important medical event.
02:13And that should be done by the physician,
02:16and that should be done in real
02:18time and documented in source.
02:21Then the CTC AE.
02:23The common terminology criteria for adverse
02:26events is how severity is determined.
02:28Severity is the grade of the AE,
02:31and that is developed that was
02:33developed in order to kind of have
02:36consistency for adverse event reporting.
02:38So everyone that's reports a
02:40grade three is using the same
02:43standards as the other another site.
02:45A specific protocol,
02:46exceptions to exit expedited,
02:48reporting the sphere which is contained
02:50in the caper and the protocol.
02:53That's a list of adverse events or events
02:55that are protocol specific exceptions,
02:58so usually those are adverse
03:00events that are expected,
03:01so they exclude those from
03:05being reported expeditiously.
03:07And then the cancer therapy evaluation
03:09program adverse event Reporting system,
03:11which is C type errors.
03:12That's the web based system that
03:15is used to electronically submit
03:17the expedited reports to the NCI.
03:21There's also two different types
03:22of reporting for adverse events.
03:24There's the routine reporting
03:26and the expedited reporting.
03:28The routine reporting is when
03:30you record the adverse event
03:31only on the adverse event CRF.
03:33The NCI.
03:34Then we'll get that information,
03:36and then annually they look at
03:38it to put in the annual report.
03:40The expedited reporting is when you
03:42submit it through seats up errors.
03:44That means it is a serious
03:45adverse event or it was required
03:47to be submitted by the protocol.
03:49And in addition to.
03:50Submitting that to cite pairs,
03:52you also need to record it on
03:54the adverse events Sierra.
03:56So the adverse PC address adverse
03:58events CRF will contain both the
04:00routine and expedited adverse events.
04:06Why do we monitor adverse events?
04:09It's for patient safety.
04:10We need to identify if there's
04:12any events happening that may
04:14be impacting patient safety.
04:16We also are able to inform the regulators
04:19and best to Gators people treating
04:21the patients on anything important
04:23that is learned about the medication.
04:25Or the treatment regimen.
04:27And then also it just provides
04:29a summary of the adverse events,
04:31which then is used to develop
04:34the regimen toxicity profile.
04:36If anybody has any questions as we go along,
04:38just please. You know,
04:41ask that and I'll just pause.
04:45For oncology trials,
04:46I think the reporting of adverse
04:49events is is challenging.
04:51Protocols are a little bit more complex.
04:52There can be multiple agents being used.
04:56Patients could have had prior
04:58therapies which will be impacting
04:59some of the symptoms that they have.
05:02They can have a lot of baseline symptoms,
05:03signs and symptoms,
05:04either based on their condition,
05:06prior treatment, or intercurrent illnesses,
05:10and they can be on a lot
05:11of different medications.
05:12So I think makes it a little
05:15bit more complicated to.
05:16So to identify adverse events and
05:18to determine if there are serious
05:20adverse event or routine adverse event.
05:25So when when a patient does experience
05:28any type of adverse event, it's very,
05:31very important that the principal
05:33investigator assesses the adverse event
05:35and documents it thoroughly in the source.
05:38The description should be provided.
05:41There should be the start date and if
05:43there isn't, if it is an SAE, I advise.
05:45Sites to enter the date
05:47that it was discovered.
05:50Enter that date in the source as
05:52well as in the seat Ipars report.
05:55Just so that we can determine
05:56if you learn of the event late
05:59that it was not a late reporting.
06:01So in addition
06:02to that, I have a a quick question.
06:04The date the site was made aware.
06:06Does that just go in the comment
06:07section in the seat up errors report?
06:09Or is there an actual field
06:11that we can document that in?
06:14That would just go in the narrative section?
06:16OK, alright, perfect. Thank
06:17you. It just makes it clear if anybody
06:20does review that report that you know
06:22you discovered it at a later point
06:24and that's why it wasn't submitted
06:26as quickly as the protocol required.
06:28OK, thank you. So in addition to the
06:30description of the event in the start.
06:32Wait, the severity which is the ctca
06:36you is used CTCA is used in the version
06:39of that will be in the protocol.
06:40So we previously used version four.
06:42We're now using version 5 and I think
06:44this fall version 6 may be coming out.
06:46So protocol will specify which version
06:48is to be used, seriousness whether the
06:52patient was hospitalized, they died.
06:53It was important medical event.
06:55Things of that nature or the
06:57attribution expected this work up,
06:58meaning what did they do to diagnose
07:00this issue? If it was something else?
07:02Had to be.
07:03Done like a CAT scan or something
07:05treatment for it.
07:06Action taken with study drug and then the
07:08stop date or when it changed in severity.
07:13Then a flow chart that I created.
07:16To kind of help with identifying whether
07:20you're going to and a who's going to be
07:24reported routinely or expedited reporting.
07:27So the first step would be to look
07:28at the adverse event, integrate it
07:30so that way you know if it's some.
07:34You know a Grade 345,
07:35which is typically the grades that
07:39are recorded doesn't mean a grade
07:41one and two will never be recorded,
07:43it just that more typically
07:45grade 3/4 and five star. Uhm?
07:49And then again, as I said,
07:50you need to assess whether a Grade
07:523A is an important medical event
07:54or the physician needs to do that.
07:57Step 2 would be to look in the
08:00protocol to see if there's any
08:02specific reporting requirements.
08:03Are there any adverse events
08:06of special interest? And.
08:09One protocol that I know your site is.
08:13Participating in is 10020.
08:17Uhm, let's see if I can pull
08:20that up real quickly.
08:23So.
08:26Fat
08:37let's see. That protocol has
08:41adverse events of special interest,
08:43so the first thing you want to
08:44do is look in the protocol and
08:46see does this protocol have any
08:47adverse events of special interests,
08:49and then review those?
08:51And if the adverse event that you're.
08:54Assessing is one of these adverse
08:56events and special interests
08:58say the patient had colitis.
09:00Then it would be reportable.
09:02It says here the following adverse
09:04events are considered special interests
09:05in patients receiving totalism.
09:07Evan must be reported expeditiously
09:09irrespective of regulatory
09:11seriousness criteria.
09:12So if that's the case and you see
09:14that it is us AE of special interest,
09:17then you are going to go ahead and submit it.
09:20You don't even have to do anything else.
09:23If there are no ayeza special
09:25interests in the protocol or the
09:27ER assessing is not one of them,
09:28then you go on to the next step.
09:31The next step is to really identify
09:33is this even an SAE doesn't meet the
09:36definition of a serious adverse event.
09:38And again, going back to the protocol.
09:41You can see.
09:45These are the definitions of
09:46an of a serious adverse event.
09:49You know there are results in death,
09:51like threatening. Hospitalization.
09:57And compared to you know
09:58and disability anomaly,
09:59important medical event.
10:01So does it meet that criteria?
10:04And if it if it.
10:08If it does not meet the definition
10:10of a serious adverse event, then no,
10:12you're not going to go any farther.
10:14You're just going to enter it on
10:16the brave advert adverse event CRF,
10:18and then you're done. If it does meet
10:21that criteria that it isn't SAE,
10:23then you're going to go to the next step,
10:25which is now is it excluded
10:28by the protocol for reporting.
10:30So the spear again are exceptions
10:33to expedite reporting.
10:35And as a note.
10:36You really should look at the entire
10:38section of the of the adverse event
10:41adverse events section because
10:43there are also sometimes additional
10:46exceptions to SAE reporting.
10:48That might inhibit the make it result
10:52in that having to report it so.
10:56This is another protocol you guys
10:58are participating in 10212.
11:09So as you see like, here's the sphere,
11:12which is the comprehensive adverse event.
11:15And potential risk list which
11:16is the caper in the spheres.
11:18This this portion of it,
11:19the specific protocol exceptions
11:21to expedite reporting,
11:22so if the patient had free round Wikipedia,
11:26which I don't even think actually
11:27great to exist for that.
11:28But if febrile neutropenia,
11:29if they have a grade 3 then it is
11:33not excluded for from expedited
11:35reporting it most of the time
11:37the sphere has a lot more.
11:41Yeah, things on here could
11:43have like say it was some.
11:45You know a neutrophil count.
11:46You know, grade grade and if it was.
11:49Grade 3 or below.
11:50It wouldn't have to be reported.
11:53So, but this this protocol then also has.
12:02As additional.
12:10Exceptions to expedited reporting.
12:14So for this so here in this for
12:16this protocol, only the AE's grades
12:19listed below do not require expedited
12:21reporting via CEATEC errors.
12:23So then you would look at
12:26this chart and see if the.
12:29Adverse event was on here.
12:31If it was then you don't have to report it.
12:33If it is not on here and
12:36it's not excluded by sphere.
12:38And it is an SAE based on the SC definition.
12:42Then it then you are going
12:44to report expeditiously.
12:46So no, it was not included on the
12:48spirit was not included in the protocol
12:51as excluded from expedited reporting.
12:53So then you are going to.
12:55Submit an essay report for that AE.
12:58However, if it is excluded
13:01then you are going to just go.
13:04To the routine reporting.
13:07And every expedited AE is also.
13:12Recorded like a routine adverse
13:14event so the adverse event CRF
13:18and rabies comprehensive of all.
13:20Non serious adverse events
13:22in serious adverse events,
13:23so everything should be captured
13:26on that one form.
13:28Does anybody have any questions
13:29about this flow chart?
13:35Is this does it?
13:36Do you find this helpful?
13:37Like does that kind of breakdown
13:38the process a little bit for you on
13:40how you're going to take an event
13:42and then assess it for whether
13:44it's an adverse event? Yeah,
13:46I have one question, so that chart
13:49that's in the NCI protocol that has
13:52the reporting timeline that says
13:55if it's grades one, two or three
13:58and its results in hospitalization,
14:00then you have to report it within 10 days.
14:03But if it's grade four or five and it
14:07is results in hospitalization or not,
14:09you have to do an immediate report
14:11in 24 hours and then a follow
14:13up or a full report within five.
14:15Yeah this this chart.
14:16Here, so this is only in the case of it.
14:20If if it's an SAE.
14:23Or an AE that's not covered by spear?
14:27Yeah, so if it's an essay
14:28it has to be an SAE first.
14:30First you have to identify is it an
14:33SAE in an SAE is will meet one of
14:37these definitions 123456 and the one
14:40that kind of captures a lot of them
14:42are the important medical events.
14:44So does the investigator consider this,
14:46you know something that's important that
14:49could really result if he's not treated,
14:51it could result in one of these other.
14:53OK, I see.
14:55So first you have to decide and once
14:57you figure out it isn't serious adverse
14:59event and then you check the sphere,
15:01you check that adverse events section.
15:02And again,
15:03it's unfortunate that it's not altogether,
15:05but you do have to check.
15:07More than one location to see
15:09if there's any exclusions,
15:11but just be sure just to make sure
15:13you don't have overreporting.
15:14Make sure you look at the entire
15:16adverse event section of the
15:18protocol to be sure you're not
15:20missing something that should be
15:22reported or should not be reported.
15:23And that's when you then use this timeline.
15:26Once you've identified that,
15:27it should be reported in this time.
15:28This chart timeline chart goes into effect.
15:32Got it OK. Thank you so much.
15:35Cynthia, can I ask a quick confirmation
15:38question just for the group?
15:40Four, so it's sometimes possible,
15:43especially, especially in hematology trials,
15:45that a patient may have a grade 4 adverse
15:48event that didn't require hospitalization,
15:51and what we would have to do in that
15:53case is basically confirm that a
15:55Grade 4 is not medically significant,
15:58and if it's not an SAE but it is
16:00a grade four, it's just a regular
16:02adverse event like the chart notes.
16:05So just because it's a higher grade
16:07doesn't necessarily mean that it's
16:09automatically going to get expedited.
16:11Reporting right
16:12exactly exactly, so let me see if this.
16:19How do we override
16:20that in this system to not report it?
16:23Yeah, I can go over that in a minute,
16:24but see like right here.
16:26Trisha like you can see here you
16:29have exception 6 that I'm reporting
16:32anemia Grade 4 so it would have to be
16:35a great fight for you to report it.
16:37Abdominal pain constant.
16:38So this is like you know,
16:40a lot of these are pretty high,
16:41so this is a must get.
16:43Hematology study and neutrophil
16:45count decrease rate for so.
16:49In those cases.
16:51The spear will pretty much dictate what
16:54needs to be reported and what doesn't.
16:56If it's a new.
16:58Regimen that there may be a
17:00little bit more concerned about
17:01it may they may want more things
17:03reported than in other situations,
17:05so it just depends on how
17:06much knowledge they have.
17:07Probably on each individual drug
17:09on the regimen as to what this
17:11fear will list as the greed.
17:14And again, then,
17:15even if the spear says this,
17:16I would look through to make sure there's
17:19no additional exceptions to reporting.
17:22OK, great so yeah.
17:23So maybe if you want to go
17:25through the adverse event.
17:27So how you override the adverse
17:28event if you want to maybe we
17:30should just finish this and then
17:31maybe we can go over and talk about
17:33C tip errors real quickly and the
17:35adverse event reporting through.
17:37Yeah I. I think going through
17:39Rave would be extremely helpful.
17:42So anyway, so this is like I said,
17:43this is the basic process that you're going
17:46to take when you have an adverse event
17:48in that you can then determine and again
17:50the the physician needs to be involved.
17:52In particular in these earlier phases
17:55just to get the grade and this.
17:59You know and how significant
18:01the adverse event is so.
18:03Then just some things to consider.
18:07When you do have an adverse event,
18:09like was it an adverse baseline symptom.
18:11If it was an adverse baseline
18:13symptom and it did not change like.
18:17It was the same grade.
18:19There was no change in attribution
18:20then it does not have to report
18:22it as an adverse event.
18:23A routine adverse event or
18:24as a serious adverse event.
18:26However, if it does change in severity,
18:29the grade increases or
18:31the attribution changes.
18:32It's now possibly or probably
18:35related to study drug.
18:36Then you would then have to enter it as an
18:40adverse event on the seat adverse event CRF.
18:43And then again,
18:44it wouldn't be an SAE unless it met
18:46all those other criteria for an SAE.
18:48Another thing that would have to be
18:50assessed is if if an adverse baseline
18:53symptoms like intermittent something,
18:54then that's fine.
18:55But if it's a kind of a finite
18:57adverse event that has a stop date
18:58and it reoccurs during this study,
19:00then it would have to be reassessed
19:02for now as an adverse event.
19:03Just because we want to know what
19:05did it reoccur because of study drug.
19:08And then you want to look at
19:10whether the patients receiving
19:11investigational or commercial drug,
19:14I believe at the recent audit the
19:16patient was initially receiving just
19:18commercial and then on day eight they
19:21started receiving the investigational drug.
19:24So during that first eight
19:26days the patient did have.
19:28What could have been considered an SAE?
19:30But because the patient was only on the
19:33commercial part of the study so far,
19:35it was not.
19:38He did not have to report it
19:39because it was an expected event
19:41for those drugs and expecting this
19:43you can really find out when the
19:45commercial drugs by looking at the.
19:47The idea for that drug.
19:49Do you have a quick question about that one?
19:52Because on the previous page it mentioned
19:53that it was if it was like a hospitalization.
19:56It's regardless of. The attribution,
20:01well, this is only for commercial drugs.
20:03If there was investigational drug,
20:05all of that applies,
20:06but for a commercial drug,
20:08unless the protocol specifies differently.
20:11They you they already have a
20:13safety profile for those drugs,
20:15so you you refer to that safety
20:17profile for that commercial drug
20:19to determine if it's serious and
20:21if you have a question about that,
20:24the safest bet is to call see tip
20:26errors and and ask them talk to the lead
20:30physician of the national Pi for the study.
20:33Talked to them about that again,
20:34as soon as it as soon as the
20:36patients on either you know,
20:38even if they're on commercial
20:39and investigational,
20:40the Pi thinks is related to the.
20:42Commercial, it doesn't matter,
20:43it still is reported because that patient
20:45also on a new regimen and part of
20:47that regiment is an investigational agent.
20:48So it goes under the
20:50investigational umbrella.
20:51The only time this applies if there
20:53are only on commercial drugs,
20:55and sometimes you might see that
20:56if the patients randomized in one
20:58arm is only the standard of care
20:59and the other one is standard of
21:01care plus an investigational agent,
21:03and then in that situation he
21:06assessment of adverse events can
21:08be different just based on.
21:10Which arm they're on?
21:12So and again,
21:13if you have a question about that,
21:14the safe route would always be.
21:16Talk to your Pi,
21:18talked to Li Pi calceta pairs and just
21:20confirm whether it should be reported.
21:23Look in the protocol, but the standard.
21:26Directions are if it's only a
21:29commercial agent, that's it.
21:30They they have a safety profile
21:32and you go by that.
21:33And if it's an expected.
21:36Event for that for that commercial
21:38drug or combination of drugs then it
21:41would not be reportable because it's
21:43almost like over reporting for the study.
21:46Does that make sense?
21:47Yeah, so I'm just gonna try to
21:50rephrase only once a patient
21:51or for the most part site.
21:53Some trials are different.
21:55Once a patient starts,
21:56the investigational drug is when
21:58we're making those SAE assessments.
22:01Yes, well, not necessarily.
22:02You're going to make them all
22:04along because you could still
22:06have an unexpected adverse event
22:08with commercial commercial drugs,
22:10so you have to look at it wasn't it
22:12wasn't an expected or unexpected.
22:14It was unexpected in serious.
22:16Then it still gets reported.
22:18So, so I'm going to go back to the example.
22:20So if a patient is hospitalized
22:23on a commercial drug,
22:25even though a hospitalization
22:27meets the definition of an SAE,
22:29it's not necessarily reportable
22:31unless it's a non serious.
22:36If the patient is hospitalized,
22:37I would definitely contact the
22:39national Pi or C temp errors.
22:42I don't know if you know if they
22:45have grade for me peneia that
22:47might be an expected event now.
22:49What was the reason for
22:50them to get hospitalized?
22:51You know what I mean?
22:52You have to look into that further.
22:53I can't really say.
22:55Conclusively that they wouldn't.
22:56That would need to be repeat reported.
22:59I think in that situation you need to like.
23:01Like I said, talk to cite pairs and
23:02talk to the National Pi and say you
23:04know they're only on this commercial.
23:06Dr is expected for the patient
23:09to have prayed for neutropenia.
23:11We're putting him in the hospital
23:12for this reason.
23:13You should report it.
23:14I think in that situation I would
23:16just for just confirm what they want.
23:21But in a situation,
23:22what we had this week,
23:23and I think you did contact setep errors.
23:27They they came back pretty
23:28quickly and said now these are
23:29expected adverse events for these.
23:31For these drugs and it does not
23:32need to be reported because
23:34they know historically been
23:35treating patients with that drug.
23:37But their blood counts are going to
23:39drop and they don't need to know that
23:40again because they already know it.
23:45I know it's a little confusing,
23:46but I don't think you need to.
23:48I don't think you need to focus too much
23:49on that because there's not that many
23:51instances there that's going to occur.
23:52It's only going to occur in that one.
23:55The protocol that you just did when they're
23:58only on commercial for that first eight days.
24:01Or in a situation where there
24:02might be two different arms,
24:031 standard of care and one is not standard,
24:05one has standard of care plus
24:06an investigational agent.
24:07Most protocols you're going to have an
24:10investigational regimen, even if it's over.
24:13The regimen has some.
24:14Standard of care and investigational
24:16agents or commercial agents and that
24:19are used that for new reason than
24:21their investigational agent, again.
24:24So most protocols are going to be
24:26under the investigational umbrella,
24:27so my my my feeling is you need to
24:31assess every adverse event for it
24:33as a E and then in your head you
24:35know if you realize this protocol
24:37has a standard of care arm.
24:39Then you just want to sit there
24:41and look at it a little further to
24:43make sure it's still reportable.
24:45But again,
24:45most most of your situations are going to
24:47be under the investigational umbrella.
24:49I think the commercial umbrella
24:51is is not very often,
24:53at least not not in our early fate,
24:54not in the phase one,
24:55and not in the early phase.
24:57Two titles that we've been doing.
24:59I think that's really helpful,
25:00so I guess forever my team standpoint,
25:03what we'd want to do is,
25:04during study startup,
25:05assess whether or not there's a
25:07commercial drug use so that we can pay
25:09closer attention to the essay reporting,
25:11which should be on less than
25:13the majority of the trial, so.
25:14That's the time point.
25:16I think that we maybe want to make that
25:18assessment because it sounds like again,
25:19it's not for all of them
25:21again and again if it,
25:23even though it's a commercial drug.
25:24If you're taking it for a new reason,
25:27it's not approved for it becomes
25:29an investigational drug.
25:30And if it's if it's not standard of care for
25:33what you're giving the patient that drug for,
25:36or if it's being combined with
25:38another investigational agent,
25:39you're looking at the whole regiment.
25:40The whole regimen has again,
25:42once on that protocol we
25:44were just discussing.
25:45Wednesday 8 happened in the the
25:47investigational drug was added.
25:50It becomes an investigational
25:51regimen and all adverse events
25:53then qualify for SAE reporting.
25:57So even if the doctor thinks it's active,
25:59they even if they attribute
26:00it to one of the other drugs,
26:02they still have to report it,
26:03because there's no guarantee that
26:05it really was could be attributed
26:07to that commercial agent.
26:08You know what I'm saying?
26:09Unless the spear excluded it right?
26:12Or it could be like a combination of the
26:14the drugs and we wouldn't know unless
26:16everyone is reporting right exactly.
26:19To be more frequent, it could be great,
26:21could be worse severity.
26:23It could be worse.
26:24So yes, so those so.
26:26You know, so I don't want to confuse you.
26:27I don't want you to not report things,
26:28I just want to know about this community.
26:31If it's a new regimen for that.
26:34On study diagnosis,
26:35then that's always investigational
26:36if if it's standard of care plus an
26:39investigative investigational agent
26:41becomes an investigational regimen.
26:43And then it's just like treated just like.
26:47If they were just on the
26:49investigation one drug so.
26:51So there is one question in the chat
26:54one of our coordinators just wants to
26:57confirm that during a hospitalization
26:59that we should be reporting out
27:01on all abnormal or all labs.
27:04Concomitant medications and AES that
27:06occurred during that stay within the EDP.
27:10And can you just confirm for us
27:12again that grade one adverse or grade
27:15one labs during hospitalization?
27:16Do those also need to be reported under the.
27:23Under the, I can't think of that lab page.
27:29An additional lab page or during
27:32hospitalization is adjust what's significant.
27:34Is it all or just what's been
27:36deemed significant? I guess
27:37is what I'm trying to place
27:38when they're hospitalized.
27:39I mean, I think they're gonna
27:40have an abundance of labs.
27:41I think it needs to be.
27:42It definitely needs to like
27:44if there's still, you know,
27:46being assessed or giving study
27:47drug course you have to follow
27:49what's on the study calendar and
27:51enter all of those time points.
27:53And then yes,
27:54I would say anything that's
27:56you know significant from the
27:58hospitalization should be entered.
27:59I I. I don't think it's realistic
28:02to enter every single lab.
28:04That they had ever drawn, but I mean,
28:06I think you need to look and see,
28:07you know, look through all the
28:09labs and if there's changes and.
28:12The the values you know if the
28:14patient goes from grade one to
28:15grade 2 and then the grade 4,
28:17you know you need to like come
28:19and enter those, but I don't.
28:22I've never been told what exactly
28:23I've never been asked that before,
28:25and I've never really looked to
28:27see that every lab is entered.
28:28I would look for significant
28:30labs and anything.
28:32You know that needed it to be
28:35reported more so than all the labs.
28:38OK, great, thank you so much.
28:40I can get more clarification
28:42on that if you like but.
28:44But yes, I mean. I I don't know my.
28:47My experience is that when
28:48they're hospitalized,
28:49I think they can have multiple
28:50draws in a day.
28:54Yes, and I know that that was a
28:56question that came up during last
28:58week's audit was to ensure that we
29:00were assessing the abnormal labs.
29:02So I I guess I jumped to that
29:04conclusion that in a hospital in
29:06the case of a hospitalization,
29:07we would only then be reporting
29:10abnormal labs that were deemed
29:12clinically significant by the provider
29:14and not all labs that were drawn on
29:16that patient for their their stay.
29:21Yes, I mean I think I would probably enter
29:23all the labs on the day of admission.
29:25You know, like I mean like 1 comprehensive.
29:28You know CNBC, you know, like.
29:30CBC you know and all that kind of stuff.
29:33Just have one baseline from
29:35when they were admitted,
29:36and then maybe like you said,
29:37anything that significantly changed
29:39throughout the study if they stayed,
29:41but they were stable throughout.
29:42And those values didn't change their.
29:44I don't see a reason to
29:45continually put everyone in,
29:46but as they have significant changes
29:48then I would enter those values.
29:51But I think putting the baseline
29:52in would be a good idea when
29:53they were first hospitalized.
29:58And that gives you kind of a baseline.
29:59Do that. You're going off
30:01up to assess the remaining.
30:02You know the remaining blood draws.
30:06OK, I think that makes sense if you if
30:08there's any other further like written
30:09guidance on that, I think that that
30:12would be. I'll ask if there's any written
30:13guidance or anything that can be, you know,
30:15concrete guidance that can be provided. OK,
30:18that'd be great. Thank you.
30:21And then again,
30:22like you're in the protocol,
30:23specific requirements reporting,
30:24and then the reason for the hospitalization
30:27hospitalization is only reported
30:29reportable if aney is associated with it.
30:31If it was a hospitalization plan plan
30:33prior to the study for an elective surgery,
30:36then that's not an SAE.
30:38If it's a hospitalization because
30:40they may have a for some reason,
30:43they have to get a port put in or
30:45something that's not going to be an SAE.
30:46They were just putting the patient in
30:48there to have that procedure done.
30:50So just some you know,
30:53all hospitalizations
30:54don't need to be reported,
30:55they're only reported if they're
30:58related to an adverse event.
31:02Just a reminders all information
31:04that's on the adverse events in
31:06Europe and in the expedited report
31:08has to be in source. So just remind.
31:13Your investigators to you know.
31:14Thoroughly document these adverse events.
31:17The protocol Trump's all
31:18other reporting requirements.
31:19So the protocol says there it's
31:22there's an exception to reporting.
31:25Or that it needs to be reported
31:26then it's reported or not reported?
31:28I mean, of course,
31:30if the physician feels like.
31:33You know has a feeling that
31:34this has to be reported,
31:35and of course he konesky or she can
31:37escalate that to the National Pi and the
31:39C type errors and then just you know,
31:42consensus consensus on whether
31:43it should be reported. Uhm?
31:46The expedited reporting CRF in
31:48Rave is just a recommendation.
31:52It's then you have to still go through
31:54that flow chart that I provided.
31:57You know the Pi needs to make
31:59the final decision.
32:00You know,
32:01based on the protocol requirements and
32:03the attributions of you know of the AE,
32:06if it should be reported.
32:08So not every time that the
32:10expedited reporting CRF says.
32:12They recommend reporting
32:14doesn't have to be reported.
32:16There should only be one
32:17estate report per course,
32:19so if the patient has even two
32:22separate unique SAE's during the
32:24same course that have you know one
32:25starts and stops and then a whole
32:27different SAE starts and stops,
32:28it still goes on one report and
32:30these first report is just amended.
32:33If there are recurrent recurrent
32:35adverse events in SAE's,
32:37they must be reported on the
32:39rave adverse events era.
32:40Every occurrence must be.
32:43Put on there, unless it's wearing one.
32:47That's not required,
32:48but recurrent Sae's you do not
32:51have to submit another expedite
32:53report unless the grade increases
32:55or there's a hospitalization
32:56associated with the recurring SAE.
32:58So with the patient.
33:01Had.
33:02You know, uh,
33:03grade four wheels go with grade 4.
33:06B Braun neutropenia or grade.
33:083 new brown neutropenia and then it resolved,
33:12and then the next course
33:13it it started up again.
33:14You'd still record that and rave,
33:16but you wouldn't have to submit another
33:18SAE report unless the grade went up to,
33:20like,
33:20maybe grade four or they ended up
33:23being hospitalized for that event.
33:24Lab abnormalities grade two
33:26and higher must be entered as
33:28adverse baseline symptoms and
33:29as adverse events regardless of
33:31their clinical significance.
33:33If you have any questions about the
33:36management of these adverse events in Rave,
33:38I would contact data management.
33:41But if you have any questions about
33:43the submission of an SAE and if a
33:45drug if an adverse event is an SAE,
33:47I would contact the seat up
33:48mirrors desk and they can give
33:51you some guidance on that.
33:53So for these slides,
33:55are there any questions that you have?
34:02Does that help at all?
34:03You got help you at all. Kind of dumb.
34:05Understand the flow of of adverse
34:07events and how you assess them. As CS.
34:15I think this was extremely helpful.
34:18So did you want
34:19me to go through? I guess you want
34:21me to go then through the UM?
34:23Let's say he reporting let's
34:24see I can go open that too.
34:26So I won't. I won't go through
34:28all of this because I think you
34:30guys have this PowerPoint already,
34:32so there's not unless you want me to.
34:34If you want me to, I will,
34:35but if you if you.
34:38If you want to, I think
34:39there are two things that came up last
34:42week 'cause we do have this from July
34:44and I think last week what we were
34:47noticing is when there's multiple
34:49SAE's in the same course and then how
34:51to like bypass the suggestion like
34:54what steps need to be taken when setep
34:57errors believe something is an SAE
34:59and we've confirmed that it's not.
35:02OK, OK so. And you know, so as you know,
35:07there's the adverse event in the
35:08expedited reporting evaluation,
35:10so you know I'll just kind of go
35:12through a general introduction and then
35:14will so you know, all adverse events
35:16are interred on the adverse events.
35:17Sierra as soon as you enter them.
35:21Then you. Have to go to the expedited.
35:28And you have to click send for evaluation,
35:30hit save, and then you're going to either get
35:33a recommendation to report or not report,
35:36and you of course want to look for any
35:37errors if there's an error in the submission,
35:40then there's going to be some kind
35:41of alert up here saying that your
35:43form did not get submitted, and.
35:45Something is wrong and most likely what
35:47is could be wrong is that on the adverse
35:50events here a maybe there's some missing
35:53information that is required in order
35:55to submit it to see to bears for evaluation,
35:57and most of the time those are the.
36:01Fields with a like a red
36:03asterisk or highlighted in red.
36:05The only one that may not be his attribution,
36:07and that one's definitely required,
36:09and they're also cannot be any
36:11outstanding system queries.
36:12They all system queries must be closed before
36:16you can send that form for evaluation.
36:19Uhm, let's see.
36:22So again,
36:22these are all the recommendations
36:24that can come back based on sending
36:28that form to the rules evaluation.
36:31And.
36:33So if you have a recommendation for none,
36:36so if you.
36:38If that's the recommendation you get back,
36:39however, you realize the protocol
36:42requires you to submit that as an SAE.
36:45Then all you have to do is click
36:49this to complete the safety report.
36:51But you're not going to change this,
36:53you're gonna leave that as it is.
36:54The recommendation stays none,
36:55but you're still going to click this
36:57and go ahead and complete the essay
36:59report as normal and cite pairs.
37:03So that's that.
37:05And then if it says to create.
37:07Uhm? Then and again,
37:10like when you say when there is
37:13none right here in this column
37:14on the adverse events here,
37:15if you're going to see
37:17the recommendation is no,
37:18and this is a derived field and will not
37:20change based on you submitting the report.
37:23It will always remain no.
37:26So just as an FY I you don't
37:27need to go in and change that.
37:28It just states that that was
37:31the original recommendation.
37:32And then if they said to create it,
37:34that field gonna say yes and again,
37:36even if you override that recommendation,
37:38it's always going to say yes in this field.
37:40The original recommendation
37:41is always going to be there.
37:44So then if you wanna override this
37:48recommendation, what you have to do
37:50is then you do go change this create
37:52to none and then that will just.
37:55Reverse the recommendation in.
37:58The report type, the due date
38:00and all that will then disappear.
38:03So it's a little confusing
38:05because if they don't,
38:06if they don't recommend it,
38:08you don't change it to create,
38:10you just leave it as none.
38:11But if they say create you are
38:13going to change it to none and then
38:14that way this page will no longer
38:16have that recommendation on it.
38:18And there's a chance.
38:19Then, if you ever had to modify the
38:21adverse event CRF and you went back
38:23and ran the rules evaluation again,
38:25it most likely you're gonna end up
38:26having to do that a second time.
38:31And then you know we don't
38:32need to go through all that.
38:33I think does that answer
38:34your question pretty much.
38:38Yes, I believe that does team.
38:40Do you guys have any other
38:42questions about that report when?
38:45It triggers us to report something,
38:46but we've gone through those
38:47steps that Cynthia went through
38:49in the last presentation.
38:52OK, no, I guess oh thank you
38:55alright. One confirmation
38:56I think we got it.
38:58I have one question so if it says say we had
39:02to change something on just a regular AE,
39:05if we had already changed this
39:08to none would the database then
39:11recommend an amend or create again?
39:14If we submitted the ease for review
39:16and it still contained the one that
39:19it thought needed to be expedited,
39:21does that make sense?
39:22I hope. I hope it does.
39:24Yes, yeah no, it does make sense, right?
39:27Yes, I think like if you
39:29haven't submitted a report,
39:31it'll come back and say,
39:32create UM. And. I would.
39:38You know that's an interesting question
39:40I I would assume if you you amended
39:43something that they recommended for
39:45reporting but you did not report,
39:48I would think that that could trigger
39:50the same situation where they might say
39:52amend and you really don't amend it.
39:54You didn't submit it as an SAE,
39:56but that's only if you had already submitted
39:59another essay report for a different SAE.
40:02In that situation,
40:03I think I would call a seat at errors desk
40:06and just ask their opinion on on how to.
40:09Modify this form.
40:10I don't know if that's has that
40:12come up for you before where you had
40:15submitted an SAE for something else
40:17that wasn't a save during that course,
40:20but the one of the events that they
40:23recommended you did not submit.
40:25And
40:26yeah, it yeah. So it came up we had
40:29a grade for white blood cell count
40:32decrease and we reported it on the
40:35form and then I had changed it to none
40:37originally since it was already reported.
40:40And of course, previously, and when I
40:42had submitted the changes for review,
40:45it then told me again to create.
40:47So it just kept telling me to create or.
40:51Yeah,
40:51but it will continue to tell you to
40:53create 'cause it's gonna have the same.
40:55It's gonna evaluate it the
40:56same as it did the first time.
40:57So each time you're just gonna have to
40:59keep going in and changing it to none.
41:01OK alright, that makes sense.
41:02That's easy enough.
41:06So that's. Yeah, so that's really dumb.
41:10I don't know if there's anything else,
41:11but really the setep errors help desk.
41:13I think that they're very helpful,
41:15very knowledgeable,
41:16so it's it's a great resource.
41:19And then, of course,
41:20the paradox data management when it comes
41:23to anything about the data entry INT array,
41:26they should be very helpful and you
41:27can always reach out to me also.
41:29And if I can't answer it,
41:30I'll make sure that data
41:31management gets back to you.
41:36So anyways, is there anything else that
41:38you wanted to review during this call?
41:42And now I can't remember if
41:43there are slides in this one,
41:44but just the if there are any slides
41:47when potentially like a second,
41:49SAE occurs within the same
41:51horse in the seat app.
41:53I think the problem we were having
41:55that arose last week was the
41:57the ticket going into the first
42:00ticket that we created in the
42:02course report or the first SAE
42:04to then add on a second SAE.
42:08Yeah, so you. So you would still be.
42:13However, you would amend that original
42:16report is the same way you would
42:18go in and then add the new event.
42:21So, uhm. At that point,
42:25as there is there a link to the to
42:27the actual report that was created?
42:32'cause if it says amend,
42:34here it says. Like edit,
42:37then you're still gonna click this.
42:39To edit the report so they say
42:41that in the directions they say
42:43you still click this and it should
42:45take you to that report that was
42:47created during this course because.
42:51My understanding is by doing
42:53this integrated system you're not
42:55supposed to be able to submit more
42:57than one SAE report for course.
42:59That was one of the reasons that
43:02they created this system. Was.
43:08Who? You know, diminish.
43:12Over reporting or creating more than one.
43:15Like duplicate data entry,
43:17minimize overreporting.
43:18Make sure that there could
43:19only be one essay report.
43:20Course was my understanding
43:22of why they come.
43:24Created the system.
43:32So should the system should.
43:36And if you find if anybody
43:37found that that's correct,
43:38then I think maybe contacting C type
43:40errors and you could let me know that.
43:42But my understanding is that this
43:44system should only allow you to
43:47submit one SAE report per course.
43:52Cynthia, we might wanna follow up with you
43:55because we had a few instances where we
43:57were able to open up a secondary ticket.
43:59And so all work with the teams and better
44:02understand like what the like, how that came.
44:04Came about because there were there were
44:08there was the ability on some of these to
44:11have two tickets open for the same course,
44:13and that's what we were correct in last week.
44:16OK, OK, so yes, if you can look into
44:19that and if you can let me know what
44:22you find out about that and if you
44:24talk to setup errors. If you can ask.
44:27How, why that occurred and if, and if,
44:30how you can prevent that in the future.
44:32And if you can let me know because again,
44:34like when you look at the.
44:37If you look at the guidelines for
44:39the expedited reporting that got
44:41that that I also gave you the.
44:45It's the.
44:49Miss CTS, you resource guide
44:51or expedite reporting.
44:53That's where I got.
44:54You know, a lot of this information,
44:55not all of it, but a lot of this
44:58information from and so like I said
45:00when they say that you have to amend a
45:02report or do anything they're directions,
45:04say, amend and then you have
45:06to click this link again.
45:08That would should take you to that report.
45:13OK, well we'll do
45:15some further investigating on our end
45:17and and let you know how that came about.
45:21Yeah, that would be good because you know,
45:23like I said that that would.
45:26The unfortunate it's it's not really.
45:29You know easy to identify how to add a
45:33second event to a report report versus.
45:39You know having the mistake of adding
45:41adding a secondary port for that course?
45:45I'm also getting some comments
45:47that Extensionally might be the
45:49difference between prior to the
45:51integration and post integration,
45:53so we'll just do a take a quick look
45:56at that and see if those studies
45:57that we have that door reporting
45:58during the course was from the.
46:01Non integrated or prior to the integration?
46:05Yeah and then. And it also it's it's
46:10really recommended you can go once you've
46:12submitted the report. Ruciane grave.
46:17You can go through the regular Ave
46:20to see temp errors to complete the
46:23narrative or anything that's not
46:25contained on the adverse events.
46:26Sierra. However, it's recommended
46:28that you always go through rave
46:31just to ensure that no change.
46:33Not that you can actually submit it.
46:35'cause if you try to submit a
46:36change that's going to field that's
46:38on the adverse events here up,
46:39it's going to get rejected,
46:41so it's advised that you just
46:43always go through rate to make
46:45any kind of amendments or updates.
46:47Never saw that report.
46:52Great, thank you.
47:00So it's anybody else have any questions or?
47:08Team, do you guys have go ahead and
47:10put in the chat or just you can unmute
47:13and just confirm if there's anything
47:15else that you wanted to review today?
47:23I'm not in Trisha.
47:24I have that flow chart just on an
47:26independent individual Word document.
47:27If you if you want that separately.
47:30You know if that would be helpful at all.
47:33I guess if you don't mind that
47:35I I really like that flow chart,
47:37so I'm hoping we can share that
47:39and that can be a useful tool
47:41when our teams are making working
47:43with the physicians to determine
47:45the reporting requirements.
47:48Yep, I'll send it to you.
47:51OK, well if you know I'm always happy to
47:54get it on the phone or answer questions.
47:57Go through anything.
48:00You know, in rave that you might,
48:02you know if I don't know the answer.
48:03Of course I will go to somebody
48:05and find the answer for you,
48:06but I'm always happy to do this.
48:08So 'cause I know it's a lot.
48:09There's a lot of changes going on.
48:11There's a lot of things to
48:12keep in mind and the protocols
48:14are getting more complicated.
48:16So I know it's not not easy.
48:21It's not, but it's really helpful when
48:23we have your support and the support
48:25of setep errors and everyone else
48:27that does allow us the opportunity
48:29to ask these questions and get
48:31answers so that we can continue to
48:33improve our reporting processes and
48:36the one thing also to remember.
48:39If you're not really sure,
48:41go ahead and submit the 24 hour report,
48:43because if you don't submit the five
48:46day report, if you find out after
48:47submitting the 24 hour report that
48:49you know what now we've come to like.
48:50It's a Saturday. We think it's an SAE.
48:53We submit the 24 hour report you come
48:55in on Monday. You do a little bit.
48:57You know deeper look into it and you
48:59say Oh no, the protocol excludes this.
49:01We didn't have to report it, just don't.
49:03So if you don't submit the full
49:05report it gets dropped so it wasn't.
49:07It never was until you submit
49:10the report the full report.
49:11It's not.
49:12It's not a you didn't report it
49:14to C temp errors.
49:15You know what I'm saying so you
49:17always have that five days to give
49:19yourself a little extra time to
49:21make sure it actually is an SAE.
49:23So in those instances where you know it's.
49:27It's a little crazy.
49:27It's late at night, you know,
49:29it's a weekend,
49:29it's whatever and you feel like you
49:30think it's an essay and you come
49:32in on Monday and realize it's not.
49:33It's not the end of the world,
49:34you just don't submit the full report
49:35and you just you just realized it wasn't.
49:37Reportable and it doesn't.
49:38You know it doesn't go any
49:39further and it doesn't.
49:40It's not considered over
49:41reporting or anything like that.
49:44That doesn't make sense.
49:46Gives that again it gives
49:47you a little bit extra time.
49:49You know better to do that than
49:51probably to have a late report.
49:53'cause you didn't have time to assess
49:54it on the weekend or something,
49:55or you thought you know you, you know.
49:58And Cynthia, can you confirm as long as
50:00we withdraw that before,
50:02like an audit type of situation,
50:04that would not then be a finding, right?
50:07I it would be if it actually got submitted.
50:09If you completed the five day report,
50:11you know there's a 24 hour
50:12report in the five day report.
50:14So you submit the 24 hour report and
50:15then you get the email saying for it
50:17says even I think in rate no, I don't.
50:19I hope it changes in rave or not, but it did.
50:21You get the email saying the
50:23full report is due on this day.
50:25If it's not submitted,
50:26then the ticket gets dropped from the system.
50:29OK, so it's really bad,
50:30so it's like really do you submit the
50:3224 hour and you don't submit the fold?
50:34And that's a fine 'cause it
50:35never got submitted.
50:36Or if you submit the 24 hour and
50:38you realize you know what we didn't
50:39have to submit this as an essay so
50:41you never submit the full report
50:43that they'll never be a record.
50:44There's no record of you submitting it
50:46like software on your end that you've got.
50:49OK, so it's not a submitted SAE because
50:50you would never submitted the full report.
50:54OK, right, that's very helpful
50:5624. Five five days, so you have to
50:59submit that full report in order for
51:01it to be submitted to see temperatures.
51:03Otherwise they drop it in the system
51:05after like I think five or seven days.
51:09OK, I think that's really helpful.
51:16So. Alright, well again,
51:20if you have any other rum.
51:22Questions about AE
51:24reporting or anything else?
51:27To do with raise just please let me
51:29know and I'm like I said I'm happy too.
51:32Get another zoom call and discuss it.
51:35Thank you so much Cynthia again,
51:36we we really appreciate your time
51:38this afternoon and I I think this
51:40was extremely helpful to just review
51:41some of these sticking points for us,
51:43so we will follow up about some of
51:46those additional questions that we had
51:48and if I I think that the one thing
51:50I had written down is just about the
51:52the labs during hospitalizations and
51:54any more clear or formal guidance that
51:56we can have and hope that you'll see
52:01improvements at our annual audit this year.
52:05I think I will I I know it's a
52:06little confusing this new expert
52:08value reporting method because
52:09it is difficult when you get the
52:11recommendation to submit and then it
52:13really didn't need to be submitted.
52:14That's some little confusing so.
52:17You know, but hopefully now you
52:19understand that even though they do
52:21say that there's they set up these
52:23protocol specific reporting evaluation,
52:25it's not completely.
52:29Protocol specific 'cause it
52:30doesn't include all the exceptions.
52:34Yeah excellent. Alrighty,
52:37well have a great weekend everyone and
52:40good holiday if you're off on Monday.
52:43Thank you very much. Thank you Cynthia.
52:45Thanks everyone for joining Happy Friday.