What is the ASAP and what you should know about it

Are you curious about aggregate safety assessment planning?
Whether you’re an experienced statistician or just starting out in the field, your work increasingly demands that you apply principles of aggregate safety assessment planning. With an ever-changing and advancing landscape filled with data and technology advancements, it is essential to stay current on this topic.
In episode, Greg and I explore what aggregate safety assessment planning is, its components, its importance for statistically informed decisions, and how it ties into patient safety initiatives.
You will be equipped with a better understanding of the fundamentals so that your efforts can make powerful contributions in research settings and support meaningful health outcomes for patients everywhere.
Stay tuned while we discuss the following key points:
  • The US FDA has been advocating for aggregate program-level safety evaluations since 1988 when the ISS was introduced (the IND Safety Reporting Final Rule).
  • Aggregate data analysis looks at all available data holistically rather than relying on individual case reports. This allows for a more complete understanding of potential risks associated with a drug or vaccine.
  • In the near future, more companies will adopt a systematic approach to aggregate safety assessment planning and IND safety reporting.
  • This process will develop a better understanding of the safety profile of drugs and ensure that patients’ safety is well-thought-of.
Sources and references:
  • Ball G, Kurek R, Hendrickson BA, et al (2020).  Global Regulatory Landscape for Aggregate Safety Assessments: Recent Developments and Future Directions.  Therapeutic Innovation & Regulatory Science, 54(2):447-461
  • Ball G, Hendrickson BA, Freedman AL, Gordon R, Crowe B, Veenhuizen MF Buchanan J (2021).  Interdisciplinary Safety Evaluation for Learning and Decision-Making.  Therapeutic Innovation & Regulatory Science, 55:705-716.
  • Hendrickson BA, Wang WW, Ball G, et al (2021).  Aggregate Safety Assessment Planning for the Drug Development Life Cycle.  Therapeutic Innovation & Regulatory Science, 55:717-732.

Greg  Ball

Owner and Consultant at ASAP Process Consulting

Greg served in the Navy and taught HS math and physics before earning his MS in statistics from Purdue and PhD in biostatistics from the University of Texas.  His research on blinded safety monitoring procedures is being developed in collaboration with statistical and clinical scientists at several pharmaceutical companies (including AbbVie and Merck).  He co-leads, with Mary Nilsson, the PhUSE Safety Analytics working group.  Greg established, with Bill Wang, the ASA Biopharm Safety Monitoring working group and has been pioneering the joint DIA-ASA Interdisciplinary Safety Evaluation (DAISE) scientific working group, to advocate for aggregate safety assessments and cross-disciplinary scientific engagement.


Webinar with Greg Ball

[00:00:00] Alexander: Welcome everybody on this webinar. We have more and more people joining and as usual, there’s always a little bit of a delay after the start of the meeting um, but I would all welcome you to the first, the effective statistician webinar of the year. And If you are new to the Effective Statistician, there is a lot of resources that we provide.

[00:00:29] We have already over 250 episodes. No, actually approaching 300 episodes this year on the podcast. And we have a lot of free content already on our homepage. So if you go to the effective statistician. com, check for the free content, there’s a link to a library where I store all the content, previous webinars.

[00:00:55] And that’s where I also will store this webinar. [00:01:00] And as you have registered for this event, you will should. Pretty easily get also kind of access there. You can, you know, just head over there. It is on a, on the so called teachable platform, which is a platform that helps to provide content in a easy and nice and digestible way.

[00:01:22] There’s one other announcement I would like to make Greg is not only talking and presenting today. He will also be presenting on the April 25th. There will not talk so much about the FDA, but he will talk about how to work effectively in a multi-disciplinary team. So Greg has over eight years working as a dedicated safety statistician and within safety, the interesting thing is that you work with a lot of different functions, you know, pharmacology, [00:02:00] epidemiology, safety experts, clinical experts, medical experts, all kinds of different areas.

[00:02:06] To get this Yeah, this weird thing about safety together, because as everybody that probably listens here is, safety is a very, very different beast to efficacy. Greg has more than 20 years’ overall experience as a, as a bio statistician has served on more varied, you know, high level platforms like, you know, safety organizations the, the, we were just talking at the introduction about, you know, the safety working groups and things like that has published quite extensively about All these different aspects and started his own company recently which is ASAP process consulting.

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[00:02:54] And if you don’t know yet what ASAP stands for, it’s not as soon as [00:03:00] possible, but we’ll get to that in a minute. So without further ado, now I hand over to Greg and give him the floor for his awesome presentation.

[00:03:11] Greg: Thanks a lot, Alexander. Yeah, so today I’m going to talk about specifically the FDA DSUR but there’s some important signals here which we can talk about when we get a little bit deeper into the material.

[00:03:27] But keep in mind that plans are nothing. Planning is everything. hopefully by the end of the talk, you’ll understand the meaning of this, if you don’t already. Okay, so. The FDA is replacing its current annual reporting requirements for INDs with a more comprehensive and informative annual FDA Development Safety Update Report, so the FDA [00:04:00] DSUR, which has been previously described in FDA’s guidance for industry.

[00:04:07] The E Two F. D. S. U. R. So you’re probably familiar with this already. So high level summary. This tool, the F. D. A. D. S. U. R. Is for both F. D. A. And sponsors working together to identify and manage potential risks and ultimately to reduce exposure of human subjects to unnecessary risks. This is another demonstration of the partnership between FDA and industry working together to protect the safety of participants in clinical trials.

[00:04:50] and to protect the integrity of the data. but also importantly, this tool [00:05:00] is going to make annual reporting process for sponsors more efficient because now there is one format for submission to FDA. And multiple regulatory authorities in the rest of the world,

[00:05:17] not that it’s completely aligned. And we’ll talk about that. That’s part of the signals I was talking about. So just touch on the major provisions and then we’ll get into a little bit more detail on a few of these. So this expands the scope compared to the annual update report it’s more comprehensive it involves clinical investigations conducted anywhere in the world, not just under an IND it expands requirement for information, for example, a cumulative number of subjects enrolled in all treatment arms are required broken down by countries and [00:06:00] regions, and also the total number of subjects planned to be enrolled.

[00:06:05] The description of all actions relevant to the safety of the drug is included. And this is by any regulatory authority or by the sponsor. Importantly, the reference safety information comes from the IB, right? So this has been a little bit of, of tugging war with between FDA and ICH and other regulatory authorities.

[00:06:34] One thing to note, all safety related changes to the IRIS I. Are needed to be included in the report. So it’s not just a summary of what occurred the previous year. The information is going to be compared to what was known before. So it’s an evolution in [00:07:00] understanding of the safety profile that that’s an important point.

[00:07:03] And need to understand that if you’re going to make best use of the D. S. U. R. Need to list all serious suspected adverse reactions and identify those that are unexpected. Sue SARS. This is where we start to get into still a little misalignment and we’ll talk about that in more detail in a minute.

[00:07:28] Some of these other things are pretty straightforward. Cumulative summary tabulation of serious adverse events, summary of safety and effectiveness findings from clinical investigations. Summary of key safety findings obtained from other sources, uh, summary of significant CMC changes, cumulative listing and brief description of all known risks and potential risks.

[00:07:58] bUt what is really [00:08:00] important in the DSUR, I think. These last two things, concise, integrated evaluation of all of the new safety information. And its kind of interesting because FDA really promotes this, right? They’re, they’re very much into aggregate program level safety assessments. So it’s kind of interesting that what they had in place before is not this it’s not surprising that they’re moving to this other than some disagreements on some things we’ll be talking about in, in a minute, and the conclusion.

[00:08:41] So you put all this information together and then you come up with the conclusions, right? What. What does this mean? And what actions are being taken or will be taken? So what is the need for this regulation? Well, it’s more comprehensive, more [00:09:00] detailed. The safety summary, it will enable the FDA to more efficiently identify and review new safety signal information.

[00:09:10] But also it’s creating a more efficient reporting process to the FDA. worldwide. So it’s going to allow regulatory authorities worldwide to have the same information at the same time. And that is big. That’s really important. So in terms of what was in place before the annual update report, it was simply accumulating and reporting data for a given time period.

[00:09:43] So there would be information about what happened the year before, right? But there’s no interpolation of this information, no evolution and understanding. So without [00:10:00] considering all previously available data from clinical trials and other sources this Could have led to delays and identification of important risks now, harmonizing the annual reporting of clinical trials.

[00:10:18] Not surprisingly, is going to enhance efficiency and provide all the key stakeholders with consolidated safety information, not just the regulators, but also investigators and patients and the sponsors themselves.

[00:10:40] So the, the FDA is current. India annual report was only intended to provide summaries of clinical studies conducted under an I. N. D. And this is a brief, description of what’s included. But you can see that compared to what we were talking [00:11:00] about before and what we’re gonna be talking about moving forward here is a lot less right?

[00:11:05] So there’s a lot more information coming together for the FDA. everybody. And to align with the rest of the world. So the E2F DSUR provides recommendations for sponsors. It provides recommendations for regulators. And it facilitates consistency among sponsors and regulators. So that that partnership I was talking about before, right?

[00:11:35] In order to really protect the safety of participants and at the same time, the integrity of the data sponsors and regulatory agencies need to partner together. And this DSUR is going to provide an update on the status of. the clinical investigations. It’s going to summarize [00:12:00] current understanding of identified and potential risks.

[00:12:04] It’s going to describe safety findings that could have an impact on the protection of study subjects. And importantly, it is examining whether information obtained during the reporting period aligns with prior knowledge of the safety of the investigational drug or if there’s new understanding. That that needs to be communicated with stakeholders.

[00:12:34] Continuing again, emphasizing it provides important advantages for safety evaluation compared to the previous annual report. So this additional safety information is going to enhance the safety of subjects. And again, ensure that regulatory authorities for all development programs are relying on the [00:13:00] same information, right?

[00:13:01] So this is going to get rid of the misalignment and the challenges with reporting different information to different regulatory authorities. So one of the key learnings from this. In order to accomplish this meaningful understanding of the evolving safety profile of an investigational drug. Is going to require a periodic analysis of all available safety information. Now, historically, this is not always been the case, right? Seum 6 came out in 2005, I think. And really clarified that we need to start doing program level safety assessments.

[00:13:52] Earlier than the submission in the ISS. So we need to move the ISS up earlier in [00:14:00] development, not, not the formal ISS, but the ISS process, the ISS thinking, the, the aggregate program level safety assessments in order to understand the evolving safety information. So integrated analysis and a summary of overall safety risks.

[00:14:20] Is going to help increase the usefulness of the safety data and help facilitate efforts to identify and assess important safety risks promptly. Now, I want to clarify a couple of things. This is not going to require. sponsors to submit information that they don’t have, right? This doesn’t create a requirement for sponsors to seek out unplugged, unpublished studies, right? If they don’t have this information, they’re not obligated to include it in the DSUR. And for example, with blinded studies, this is [00:15:00] not a requirement to for study. Teams to unbind ongoing blinded studies. So in preparing the D. S. U. R. For blinded studies while they’re ongoing study teams could estimate numbers for those studies. Now there’s a requirement that the D. S. U. R. Is published within 60 days of the data lock point, which revolves around the I. N. D. Date. That’s not going to line up with other regulatory agencies. So this requirement can be easily waived so that you can choose a date that lines up with the the global date global birth date.

[00:15:44] Another thing is the FDA really wants program level, so product level, really. But often If the product is being developed for multiple indications and in [00:16:00] diverse patient populations, it may not make sense to combine. All of the studies together. But this should not be explained in the DS.

[00:16:10] You are. This should be waived before the DS. You are and then separate DS. You are could be produced for. All of the needed indications.

[00:16:23] So let’s talk a little bit about the D. S. U. R. This provides a thorough annual assessment of clinical investigations conducted and safety information is collected during the reporting period that are related to the investigational new drug. So this is a requirement to have Aggregate program level safety assessments at least once annually.

[00:16:49] Now, companies probably are going to need to do this more frequently, maybe quarterly, for example, to understand the evolving safety profile. [00:17:00] And to be able to prepare and communicate consistently and authoritatively in, in publications like the DSUR and, and other safety related reporting of information.

[00:17:14] Now this is for all ongoing or completed clinical investigations conducted anywhere in the world on behalf of the sponsor evaluating the drug, including clinical investigations not conducted under an IND. Again, they, they want this product level. If, if you don’t want to do it, then you need to get a waiver.

[00:17:35] I’m not going to sound off on all of these they’re, they’re listed here in the slides. You can have the slides after the show. There’s a couple of things I, I want to point out there’s, there’s an executive summary that summarizes everything. The table of contents is supposed to be robust enough that it’s easily searchable, so they can find the [00:18:00] information they’re looking for.

[00:18:01] A lot of these other things is just listing obvious, important safety information. One thing we need to talk about, though, are the safety data tabulations and the line listings. This is where the differences persist, and we need to understand those a little bit better. Some other things that are pretty obvious at the bottom two important things, the overall safety assessments.

[00:18:27] So this is really a paradigm shift from before in order to prepare for the DSUR and other documents reporting the program level safety companies are probably going to need to Implement a new process an aggregate safety assessment planning process. Which if we have time, I’ll talk about after the show here and the conclusion.

[00:18:52] So the overall safety assessments brings all the information together in the conclusion makes sense out of it. What does [00:19:00] it all mean? What actions are going to result from This understand this new understanding of the safety of the drug. So here’s the difficult part. This is where the differences remain.

[00:19:15] Right? So there’s slightly different information in the FDA. D. S. U. R. versus the D. S. U. R. used around the world. And this comes from differences in terminology in safety reporting standards. FDA recognizes anticipated events, for example. Other regulatory agencies don’t. Except this, this this term yet for reasonable possibility of causal association, this could be determined by either the investigator or the [00:20:00] sponsor worldwide.

[00:20:01] Us is insisting that it is determined by the sponsor who has a better view of everything to make this determination. And I got to say that even the EU and other regulatory agencies agree with this when they’re making the reference safety information. The reference safety information is determined by the sponsor and its aggregate program level safety assessments.

[00:20:31] Where the differences start to happen is in the the safety reporting, right? So, when it’s suspected as opposed to recognized. So, these differences are going to come out here. All serious suspected adverse reactions need to identify those that are unexpected. This is related to the R. S.

[00:20:55] I. And the I. B. Right. So that’s a major [00:21:00] concession by the FDA. And this is where I want to talk about One of the signals that this reveals to me the FDA for a long time has been trying to advocate for their I. N. D. Safety reporting final rule and anticipated events. And that has created some challenges, right?

[00:21:25] Well, recently we published a paper demonstrating the alignment between FDA and industry, at least in the US on safety reporting. So, it was published, the final rule was published in 2010. The companion guidance was finalized in 2012. The first draft guidance came out in 2015. So the FDA has been trying to get alignment with industry all this time.

[00:21:55] We wrote the paper a couple of years ago. Last year, they came out [00:22:00] with a new draft guidance. And my expectation is that they’re going to be finalizing that pretty quick now that there is alignment with industry. And so importantly here, right, the same challenges that the industry saw with what the FDA was requiring.

[00:22:22] Are the same challenges that the regulatory agencies and other regions have identified. So now that U. S. has regained alignment over these challenges. I expect that the FDA. Is envisioning that the other regional regulatory authorities are going to be able to also re harmonize with this new approach.

[00:22:55] So I think this is signaling here. FDA is making things is [00:23:00] as much aligned as possible. There’s only a couple differences that show up right here. But I think they expect the FDA expects that eventually other regional regulatory authorities Are going to align more closely with the safety reporting final rule.

[00:23:18] Now that we have managed in a controlled approach for dealing with the unbinding of. Serious adverse events and related information. The other things here are straightforward and not an issue. The other important thing is the overall safety assessment. So, this is a concise. integrated evaluation of all new clinical, nonclinical and epidemiological safety information obtained by the sponsor during the reporting period relative to previous knowledge of the drug.

[00:23:57] So this is where you’re going to need Some [00:24:00] kind of aggregate safety assessment planning process. Now, this overall safety assessment is not intended to require a repeat of information, from the previous sections. And it would require an interpretation of the information and its implications for the IND.

[00:24:21] Relative to what was known before and explain how safety information obtained during the reporting period integrates with what was already known about the drug. They also expect a benefit risk kind of assessment and here’s a listing of all of the things. They’re straightforward. No real controversy here.

[00:24:45] And then the conclusion. So this brings it all together, right? So the, the summary brings all the information together and the conclusion identifies what this means, [00:25:00] right? And what actions it’s going to lead to both that are underway and will be taken in the future. So if you want to comment on this, you need to do it by March 9th.

[00:25:15] There’s still plenty of time a couple months., any final rule based on this proposed rule would become effective 30 days after the final rule publishes in the federal register. So it’s going to be some time before they publish it right if they’re taking comments till March 9th, but once it’s published you have 30 days.

[00:25:40] And then compliance is expected within half a year after that. So that took a lot of time. I, I was planning to talk a little bit about the aggregate safety assessment planning process, but let me turn it back over to. [00:26:00] Alexander, and we’ll see how we want to finish up this, this webinar.

[00:26:06] Alexander: Yeah, so I think first, thanks so much for the great 25-minute presentation about what’s going on here. I think it’s a, it’s a really big change and will require a lot of additional resources to, to get all that done and to make sure that All these requirements are fulfilled and as you just shown on the last slide. Well, if it gets published, then you really should have everything in place to do it because otherwise you’ll be really, really running late.

[00:26:41] The overall kind of guidance here, I think, for me, just thinking about myself as a researcher, as a as a patient is very good because I think we’ll get a very, very comprehensive overview of what’s really going on much earlier than [00:27:00] the actual submission. So by the time it gets to submission.

[00:27:06] You’re probably going to have less work because, well, you already have a lot of done work done. Of course, there’s, there’s always additional things coming. But given that you have spent a lot of time through this ASAP, and if you probably heard what just Greg said about what it means you should be in a good place.

[00:27:27] Greg: Yeah, I want to emphasize that point. In the past, the first time that, that companies had looked at aggregate program level safety information was at the time of the submission and, and the ISS and what this DSUR are. Is requiring right in, in development, you’re looking at aggregate program level safety data at least once each year, even before the submission.

[00:27:56] And that’s a good thing, right? Because in the past. [00:28:00] If the 1st time you’re looking at the combined data. Is when you’re creating the. You bring all that information together. You have more power and precision. You’re going to find some things that you need to understand better. So it’s going to lead to more analysis.

[00:28:19] So it’s going to be a scramble at the end, right? It’s going to be a fire drill. But now you’re looking at these things. before. And by the time you get to the I. S. S. You should be pretty much ready, so it should go smoothly. This this should streamline the I. S. S. And also continuing into post marketing when you have successful drugs that are marketed, and there are additional studies to expand the label, right?

[00:28:47] There’s more information. So the process continues. You have to add on to the I. S. S.

[00:28:54] Alexander: Yep, there’s a question actually by Nelson. Thanks Nelson. He asked whether there’s any [00:29:00] specifics for how to submit the new reports. Any ease up. I don’t know exactly what that stands for, but, but Nelson, you can also kind of put on you.

[00:29:11] Video and audio and ask a question directly, but I guess it’s about the format itself. How’s that looks like?

[00:29:19] Greg: Maybe he’s talking about whether it can be submitted electronically. Yeah, that’s it. Yeah. I mean going forward, everything is going to be electronic. If, if you wanted to submit it hard copy, I think you would have difficulty. They may not accept that. I, I don’t know, but electronically. You, you certainly can.

[00:29:41] Alexander: I wonder whether that will make it possible in the future to submit more than just PDFs and stuff like that. So that that would be interesting part.

[00:29:51] Greg: Well interesting that you bring that up. We’re in discussions most notably through fuse. We’re, we’re going to have what [00:30:00] we call community forum. The next couple of months, we’re going to have one each month and, and we’re. Talking about how we’re reimagining a safety submission. So in a submission, the way it’s typically done is you basically submit static tables and listings, right?

[00:30:20] But that doesn’t take advantage of all of the technology that’s available. So we’re going to be talking about how we could leverage technology better in a submission and actually provide, interactive safety graphics. In a submission to help communicate the important safety information, right? And to give some flexibility to regulators when they review the, the, the safety information that they can look at the information different ways, you know, in subgroups that are defined ahead of time and, and this might also improve the efficiency because or change. [00:31:00]

[00:31:00] No matter how many tables and listings and figures you send in a submission, there’s always more questions, right? But if you have some flexibility to look at the, the data different ways. Then they might be able to provide their own answers, and then they won’t have to go back and forth with an iterative process that can be very time consuming.

[00:31:24] So again, this, this is all about that partnership between regulatory agencies and, and sponsor companies, right? Trying to understand the safety data, to consistently communicate the safety data to all important stakeholders.

[00:31:41] Alexander: Yeah, yeah, I think that is that’s where the future goes. Have interactive data visualizations, especially on the safety side.

[00:31:49] So that helps you to support the general workflows that you have anyway. Yeah. So where you want to kind of. Dive [00:32:00] into the data deeper on a, you know, on the subgroup on a by patient level. But then also, you know, go back to the, to a more global view backwards and forwards without kind of flipping through hundreds of tables and listings which is quite tedious.

[00:32:18] Greg: And in the process of doing this, we have to consciously recognize that safety is different than efficacy. And we need to set up a process that is designed for safety, right? Currently, clinical trials are designed for efficacy. Studies are designed for efficacy for the primary efficacy endpoint, right?

[00:32:42] And the rules are very well established. And we have the most powerful test for efficacy, but for understanding safety, right? It’s a different process. It’s not a testing and confirming process. It’s a learning and decision making process. So we need to set up a [00:33:00] process that can leverage the scientific expertise and medical judgment of multidisciplinary teams in regulatory agencies and in sponsors. In order to understand the safety profile of these drugs that we’re developing. Yep.

[00:33:18] Alexander: Yep. And that is really a very, very important point. So, so if you have just been multitasking, which I can understand we’re all sitting in PCs all the time, and there’s some email coming up on your chat coming up.

[00:33:33] If you’re multitasking, it’s a moment. Come back now because now it’s really, really important. So let’s talk about this. ASAP. What is that? And why is it so important? Could you just repeat on that?

[00:33:50] Greg: Right. So I highlighted in red some areas that are requiring aggregate program level safety assessments, right? In the [00:34:00] DSUR. But the DSUR is not the only document that is requiring ASAP. communication of the aggregate safety profile. There’s lots of documents throughout development, even into post marketing, where you companies need to consistently And authoritatively communicate the safety story. And to do this, you need a process, right?

[00:34:24] That is championed by a multidisciplinary group responsible for the aggregate program level safety assessment. And just like in studies, right? You have a study, you have a protocol. That you have this document that explains exactly what you’re going to be doing. We need a similar thing for aggregate safety assessment planning, right?

[00:34:49] You need these planning documents. Now, the difference between efficacy and safety, though, for a study, what ideally you would [00:35:00] have one protocol and it would never change, right? And you would plan it. You’d close your eyes. And when you have all your data, you would analyze it according to the protocol for safety.

[00:35:13] You have this planning docket. It’s a living document, right? And it facilitates the cross disciplinary scientific engagement of all of the relevant disciplines coming together to understand the safety. And its program level, right? And it’s ongoing and you’re going to have studies that come online and complete and more studies come online and complete and the knowledge is going to evolve and you can update this document at any time that there’s a new knowledge about the safety profile that needs to be incorporated in the safety strategy.

[00:35:49] Alexander: Yeah, and this, I think my understanding is you need to update that at lots of time points, you know, and not just kind of after you have a [00:36:00] database log, you update it when you have, you know, could be even external information coming. Yeah, this may be another drug that have a similar method of action, where they is and they publish about a certain kind of rare side effect.

[00:36:16] Well. I guess you need to take that into account and, you know, update you’re processes to, to look into this information. Yeah. Or there’s a, you know, the FDA becomes aware about a certain kind of class effect that they have seen in other areas, and you have probably been maybe been in these situations where you get a question from the FDA about a side effect and you say, where’s that coming from?

[00:36:43] Yeah, that’s because they, you know, they have seen another sponsor and they have a similar truck and they have seen the side effects. So they want you to look into it. So there’s all this information that come from all kinds of different sources. So you then need to take them into [00:37:00] account. And that’s what I think you mean by having something like a living document and a process that.

[00:37:07] Takes all these kind of different things into account and the way you can show to respond to regulators. We have everything under control and you’re also yourself as a sponsor, as a company, as a project team can feel like you have everything under control. Isn’t?

[00:37:28] Greg: Right? And very important point here. I think the FDA loves this idea of having an aggregate safety assessment planning process. I think the most common word in the final rule was systematic. The FDA and you and other regional regulatory authorities want a systematic program level safety assessment. So why are they not requiring an ASAP [00:38:00] or something like an ASAP, right?

[00:38:02] Well, I, I thought about this for a while and it became obvious to me because the way we’re developing it, the way sponsors are developing the ASAP, this is for the sponsors. This is an internal process that facilitates the multidisciplinary teams working together to understand the safety profile to identify safety topics of interest that they want to understand better before they make a determination of.

[00:38:35] Whether this is an important identified risks or not before it gets labeled or not, right? So if it’s going to serve in this purpose, and this is a great purpose, right? And this is going to help companies understand the safety profile and communicate it consistently in the DSUR and other documents, right?

[00:38:55] And if the FDA were to include this in a guidance [00:39:00] somewhere, then it would become. required, right? And then if you had an audit or an inspection, that would be auditable, right? And then that would corrupt the purpose of this process, right? Because now if that were to happen, then companies would have to say, Oh, well, if, if, if we identify this as a safety topic of interest, and then this gets, Audited, then it’s going to be on the public record, and then we’re going to be held legally responsible for this event, right?

[00:39:30] And then it’s going to corrupt the purpose of this process. So, the FDA is 100 percent behind this, and many times they’ve said in presentations at scientific conferences that they really like what the industry is doing with this. But they’re leaving it in industry’s hands so that we can develop this process for our own purposes as a learning and decision making process to understand the safety [00:40:00] profile and to consistently communicate it in the DSUR, in the ISS. In the CTD in every other publication of the safety profile of the drug.

[00:40:12] Alexander: So, if you now think as a participant here, I don’t know, we have this if we have it. How good is it? You have a good opportunity now to work together with Greg, because since he left his last job, he is now working as a consultant.

[00:40:36] So you can reach out to Greg to actually, you know, help you either set up these processes. Or check these processes, improve these processes, and learn from what are best practices, where are things going, what can you do to make sure that you always can authoritatively tell your [00:41:00] safety story for all the different components that you have.

[00:41:03] Now, Greg, how would such a, you know, Consulting look like, what, what would be kind of the benefits for, for working together with you?

[00:41:14] Greg: Right. Ultimately I want to help companies get this implemented because it’s going to help them. And the ASAP is an idea that is publicly available, although there’s very little experience with it.

[00:41:30] So companies are going to struggle setting this up in their first couple of programs. So what I’m offering is really a cure for this, right? This is not. Like an addiction to a drug, and then you need to get more and more of that drug, right? This is a cure. You

[00:41:50] Alexander: need to hire Greg and then you need to hire him again and again and again. No, no, probably not. So

[00:41:58] Greg: it’s really just communicating [00:42:00] this idea socializing this idea, helping companies implement this. We, we developed this at Merck. And it took several years, and a big resource intensive team developed this process, and then we implemented it in a couple programs, and we learned from that over a couple more years, and, and we implemented it in, in the second wave of programs.

[00:42:28] So this idea is not a theoretical idea. This is something that has been developed and implemented and it works really well. And if companies are interested in doing this, I can help facilitate the process. Now but what I want people to understand you know, it’s, they may feel a little bit uncomfortable buying into this idea.

[00:42:51] So I’m happy to come to any company, no cost to give a webinar to explain the [00:43:00] value proposition of having an ASAP process. And the DSUR is just one example of that.

[00:43:07] Alexander: Now, that’s a really, really nice offer to I hope you just got that and wasn’t weren’t distracted. You can just send Greg an email, ask him, hey, let’s jump on a call have this discussion, set up a meeting where you invite your relevant cross functional stakeholders, and have Greg explain about what this is, what is the goal, where are the learnings, We appreciate it.

[00:43:34] What are the typical kind of problems that were there in the past and how can you can leverage that to make sure you’re always up to date with, with your analysis on, on the safety side.

[00:43:49] Greg: Or even, in a more non threatening way, I have a website that I just created last, well, had created. I’m not really [00:44:00] capable of creating my own website, but I have a great website, I gotta tell you. You can go to this website and look at some of the material. And there’s a, a way to send me an email saying that you would like a free webinar. Or

[00:44:13] Alexander: you can just, you know hit reply to the emails that you got from me for this webinar.

[00:44:20] Hey, I would like to talk to Greg and then we’ll make the connection.

[00:44:25] Greg: Yes, that would be an easy way too, if you’re comfortable with that.

[00:44:30] Alexander: Any other questions from the people on the call now? Any questions about the topic? What’s coming in terms of the FDA? Any questions on Greg helping you? You can also just, you know, open your mic and ask a question. Yeah, small, small group now. So, so that’s, that’s no problem.

[00:44:55] Okay. Otherwise, thanks so much. Yeah. As a [00:45:00] short summary if you want any further help from Greg in terms of the aggregated safety analysis planning process, feel reach out to him or to me directly and and we’ll make the connection and you can get a free webinar specifically designed for your company to to get an introduction into this, We’ll make the slides of this available for everybody.

[00:45:30] And of course, we’ll put the recording into our library of the effective statistician. And so you will be able to then, you know, get all of that there and have a have a further look into this. So if you liked this and you want to share it, share it with as many colleagues as you would like, because all of this is free. And thanks so much, Greg, for being here on the first webinar of the year.

[00:45:59] Greg: Thanks a lot, [00:46:00] Alexander. And thanks, everybody. Have a good day.

[00:46:02] ​

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