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Ähnlich wie Finding a drug safety solution for you - Embase and PharmaPendium - Webinar 25 Oct 2012inar. 25 oct2012
Ähnlich wie Finding a drug safety solution for you - Embase and PharmaPendium - Webinar 25 Oct 2012inar. 25 oct2012 (20)
Mehr von Ann-Marie Roche
Mehr von Ann-Marie Roche (20)
Finding a drug safety solution for you - Embase and PharmaPendium - Webinar 25 Oct 2012inar. 25 oct2012
- 1. Welcome to our drug safety webinar! Featuring the Embase and PharmaPendium combined drug safety solution Your host: Ann-Marie Roche Your presenter: Pooja Jain
- 2. About us
- 3. Need to know • Your control panel: – Questions for asking the presenter a question or making a comment. – Option for full screen view • Questions during the webinar and time for Q&A at the end.
- 4. Finding A Drug Safety Solution: Finding A Drug Safety Solution: Embase + PharmaPendium Embase + PharmaPendium Presented By: Pooja Jain, M.Sc., MBA Date: Oct 25 2012
- 5. ••Embase is an online information Embase is an online information PharmaPendium is the only online PharmaPendium is the only online source of biomedical literature that source of biomedical literature that resource to allow drug development resource to allow drug development serves pharmacovigilance reporting serves pharmacovigilance reporting teams to efficiently extract: teams to efficiently extract: needs by broadly tracking adverse needs by broadly tracking adverse events from comprehensive high- events from comprehensive high- ••Best-in-class drug development Best-in-class drug development quality sources. quality sources. information information ••Embase records are deeply indexed Embase records are deeply indexed ••Allavailable FDA approvals since 1938 All available FDA approvals since 1938 using our Emtree thesaurus to make using our Emtree thesaurus to make ++EMA since 1995 ++more EMA since 1995 more searching faster, more accurate and searching faster, more accurate and more specific. Emtree lists more than more specific. Emtree lists more than ••More than 1.5 million pages of drug More than 1.5 million pages of drug 60,000 preferred terms and over 60,000 preferred terms and over reviews reviews 260,000 synonyms, including generic 260,000 synonyms, including generic and trade names of drugs. and trade names of drugs. ••More than 4,000 drugs covered More than 4,000 drugs covered ••Compared to MEDLINE, Embase has Compared to MEDLINE, Embase has ••Comparative exposure data Comparative exposure data over 2,000 more journals in addition to over 2,000 more journals in addition to conference reports. In total Embase conference reports. In total Embase ••Regulatory precedents Regulatory precedents indexes over 7,000 journals. indexes over 7,000 journals.
- 6. Acarbose example “Acarbose” search in Embase Filter by “adverse event” Filter by “liver toxicity” Identification of relevant articles Identify any warning Reports of post- Adverse events signs that there may Adverse event not marketing adverse reported to affect be drug induced reported in labeling events patient compliance liver toxicity Can we find Did we actually find evidence of these Could we have Was there any evidence of this in adverse events at known about these evidence of this the approval the preclinical and adverse events before the drug was package? How do clinical stages before the label approved? we mitigate risk before drug was updated? moving forward? approval?
- 7. Indexing allows for easy to find information that would otherwise be missed
- 8. PubMed returns less than one third of results.
- 9. Acarbose example “Acarbose” search in Embase Filter by “adverse event” Filter by “liver toxicity” Identification of relevant articles
- 10. What information would you have missed that would pertain to critical post- marketing events?
- 11. Search of “acarbose” in Embase
- 12. Search of “acarbose” in Embase, filtered based on adverse drug reaction
- 13. Filter further on “liver toxicity”
- 14. Acarbose example “Acarbose” search in Embase Filter by “adverse event” Filter by “liver toxicity” Identification of relevant articles Identify any warning signs that there may be drug induced liver toxicity Was there any evidence of this before the drug was approved?
- 21. Summary • Link critical post marketing findings to the drug and validate its relevance in the context of the studies that were performed as part of the drug approval process • Look at post marketing findings and understand how they could be relevant across different drugs and drug classes • Get directly to the study that was done and now find ways in which study designs could be optimized to reduce the chance of seeing those same events take place with a drug that you are currently developing
- 22. Acarbose example “Acarbose” search in Embase Filter by “adverse event” Filter by “liver toxicity” Identification of relevant articles Identify any warning Reports of post- signs that there may marketing adverse be drug induced events liver toxicity Can we find evidence of these Was there any adverse events at evidence of this the preclinical and before the drug was clinical stages approved? before drug approval?
- 23. Filter further on “liver toxicity”
- 40. Summary • Found postmarketing adverse event reporting in the Japanese demographic • Found drugs within the antidiabetic drug class which demonstrated similar adverse events in the Japanese demographic and were then able to do comparative adverse event analysis on those drugs • Found extracted drug safety data in both preclinical and clinical studies across different drug classes
- 41. Acarbose example “Acarbose” search in Embase Filter by “adverse event” Filter by “liver toxicity” Identification of relevant articles Identify any warning Reports of post- signs that there may Adverse event not marketing adverse be drug induced reported in labeling events liver toxicity Can we find evidence of these Could we have Was there any adverse events at known about these evidence of this the preclinical and adverse events before the drug was clinical stages before the label approved? before drug was updated? approval?
- 43. Article: “Medical Management of Metabolic Dysfunction in PCOS”
- 49. 2008 label
- 50. 2011 label
- 51. Summary • Found postmarketing adverse event reporting in the Japanese demographic • Found drugs within the antidiabetic drug class which demonstrated similar adverse events in the Japanese demographic and were then able to do comparative adverse event analysis on those drugs • Found extracted drug safety data in both preclinical and clinical studies across different drug classes • Found adverse events not yet reported on the label
- 52. Acarbose example “Acarbose” search in Embase Filter by “adverse event” Filter by “liver toxicity” Identification of relevant articles Identify any warning Reports of post- Adverse events signs that there may Adverse event not marketing adverse reported to affect be drug induced reported in labeling events patient compliance liver toxicity Can we find Did we actually find evidence of these Could we have Was there any evidence of this in adverse events at known about these evidence of this the approval the preclinical and adverse events before the drug was package? How do clinical stages before the label approved? we mitigate risk before drug was updated? moving forward? approval?
- 53. Was there any evidence of lack of patient compliance pre drug approval?
- 55. Summary • Found evidence that patient compliance was an issue with acarbose due to its adverse events • These concerns were clearly expressed in the approval package and should have been further considered before launching the drug on the market • Now if you are facing similar adverse events in your clinical trials, what information can you find that can help you mediate that risk of patients withdrawing from your drug?
- 56. Acarbose example “Acarbose” search in Embase Filter by “adverse event” Filter by “liver toxicity” Identification of relevant articles Identify any warning Reports of post- Adverse events signs that there may Adverse event not marketing adverse reported to affect be drug induced reported in labeling events patient compliance liver toxicity Can we find Did we actually find evidence of these Could we have Was there any evidence of this in adverse events at known about these evidence of this the approval the preclinical and adverse events before the drug was package? How do clinical stages before the label approved? we mitigate risk before drug was updated? moving forward? approval?
- 59. However a combinatorial drug therapy of acarbose and metformin is not approved yet by the FDA or EMEA. Was this ever tested before?
- 62. Where do we go from here?
- 64. Summary • Found evidence of acarbose plus metformin combination therapy in recent clinical studies • However the same combination has been considered by the FDA before • Gained insight into the risk factors of combining therapies where both drugs have similar adverse events • Found a possible way of mitigating that risk of patient withdrawal if that type of combination therapy were to be explored again
- 65. Acarbose example “Acarbose” search in Embase Filter by “adverse event” Filter by “liver toxicity” Identification of relevant articles Identify any warning Reports of post- Adverse events signs that there may Adverse event not marketing adverse reported to affect be drug induced reported in labeling events patient compliance liver toxicity Can we find Did we actually find evidence of these Could we have Was there any evidence of this in adverse events at known about these evidence of this the approval the preclinical and adverse events before the drug was package? How do clinical stages before the label approved? we mitigate risk before drug was updated? moving forward? approval?
- 67. • The Q&A will be sent to you by email. • For more information and questions please contact bdtraining@elsevier.com • Check out upcoming and previous Embase and PharmPendium webinars at http://www.embase.com/info/embase-webinars and http://www.pharmapendium.com/info/pharmape ndium-webinars. Please fill out the survey Please fill out the survey that appears on your that appears on your screen after leaving the screen after leaving the webinar. webinar.
Hinweis der Redaktion
- Embase is developed and maintained by Elsevier and to briefly put it into context, Elsevier is serving 3 main areas of interest to you, Biology, Chemistry and Medicine. [first click] Embase is one of the products serving your needs in these areas, we also have Reaxys, our Chemistry workflow tool and I will be presenting a webinar on Reaxys tomorrow, Pharmapendium, giving searchable access to all FDA and EMA approval documentation and our new target finding and validation tool, Target Insights. [second click] Sciverse ScienceDirect provides full text access to over 10 million journal articles and is continuously looking for new and novel ways to enable further understanding of the scientific literature through applications and new article formats. Sciverse Scopus is our all science database, illumin8 enables product and partnering decisions for R&D and innovation professionals working at the front-end of innovation and Sciverse is a lens on the worlds research activity. And so to todays Embase session…
- We will be placing the webinar slides and recording online so you can listen to it again, in your own time. During the session you may send us your questions by using the chat or Ask a Question function on the webinar control panel. We will answer as many of your questions as possible throughout the webinar and all questions will be included in a complete Q&A and sent to all attendees by email, as well as a link to the recording. If you wish to have a full screen view, please click on the red arrow. Your control panel will be hidden. Click again on the red arrow to see your control panel again.
- In order to show the depth and breadth of information, we will choose a drug that was approved in 1995 just so we can show you how examples of much information you can access when having both PP and Embase as there is a lot of rich data that we can extract out.
- Before I proceed, I will just mention that here [CLICK] I am showing some smaller screenshots, but then I will show a full screen view so you can see what the results look like a bit better. The purpose of the smaller screenshots is to help you visualize how to initially navigate Embase. So here you will see what Embase looks like when you go on the home page. Now due to time limits, I am not going to go into all of the functionalities of Embase. You will be prompted to fill out a short survey at the end of this webinar. By filling out your information, we will have the opportunity to contact you about the products that you indicate you are interested in learning more about and then we can really show you a more in-depth product demo. With that said you will still be able to follow along as I have made sure you can get a good grasp of how the products can help you answer some key questions you have pertaining to drug safety. Therefore we are going to largely focus on the specific functionalities and features that pertain to the examples that we will demonstrate. So again, here you see the home page of Embase. Now to find information related to Acarbose specifically, we can click on the tab named “drug” to get more relevant searches. [CLICK] We can actually choose from a number of drug subheadings that can lead us to information that is more relevant to an end user. For the example that we will show today, we will first do a search with just the drug name, acarbose, alone and then we will later on show you the results we get when we choose “adverse drug reaction” as a subheading since our examples are focused on drug safety. Just by doing this one initial search, we will demonstrate the depth and breadth of information that you can access using Embase and PP together as a comprehensive source for drug safety information.
- [CLICK] Here we have a screenshot of a search that was performed with just acarbose alone. We can see we get almost 5000 results. Now just to show you how much information you would have missed if you relied on PubMed alone, [CLICK] if you do a simple acarbose search in PubMed, you get less than one third of the results. This is largely due to the fact that PubMed does not do full-text searching. So a lot of the data that you can find in the body of the article, you will miss out on. Hence if the words that you are searching for are not in the title, abstract, keyword list, you lose a lot. And this is a huge risk to take if you are working in drug safety.
- In order to show the depth and breadth of information, we will choose a drug that was approved in 2004 just so we can show you how much information you can access when having both PP and Embase as there is a lot of rich data that we can extract out.
- As we go through the examples, we will be pointing out some articles that you would have missed if you used PubMed exclusively.
- So let’s look at a larger full screen view of just the acarbose search. You will see your search query displayed here [CLICK] . Your results showed here [CLICK]. And additional filter options shown here [CLICK]. Here the filters are drugs, disease, study type, journal title, publication type, and publication year. I will talk about these filters a bit more on the next slide. Now since your search results are so large, one thing we can do, which we mentioned earlier, is to filter based on adverse drug reactions from the drug tab we showed earlier. So on the next slide you will see how we can narrow down the search results even further by filtering records on “adverse drug reaction”.
- Now we have gone from almost 5000 records to almost 1000 articles. On the left hand side, I have an expanded view of one of the filters, Disease. Here you will see the top 25 terms listed with the highest frequency from my search query. To narrow down the results even further, we can look at liver toxicity since liver toxicity is one of the main reasons why drugs can fail either in the clinic or have serious issues post-approval.
- Now we have narrowed the results to just 194 results. We have a highly relevant set of records now and we can go in and see what kind of insights we can find. And all of this literally just took a few minutes, so it saves end users a lot of time. We will be referring to this result set very often during the presentation since we will be pulling a lot of interesting articles from this search query. [CLICK]. By looking at our results, one article that may pop out is the one that mentions elevated transaminase levels in the title. [CLICK] If we look at the abstract, we can see that acarbose is no where to be found in the abstract. Hence this article would have definitely been missed in PubMed. But if you click on the index terms tab, [CLICK] you can see the list of terms which are present in the full text, and acarbose is indeed listed here. Hence you can see that it is a relevant article.
- So we are now at this point where we are going to now look into PharmaPendium and see what information we can find.
- So now, we can switch over to PharmaPendium. This is the home page.
- So let’s start off with a search that will search records containing the word “transaminase” and we can restrict that search to just “labels” to see what drugs actually had data related to transaminase on the labels themselves.
- Here we can see that we actually get over 1500 results. You can now actually compare information from different drugs to see what kinds of elevated transaminase levels were found. This kind of comparative drug view is only visible in PharmaPendium. And this is a huge value driver for end users. To be able to compare data amongst drugs which are targeting the same indication or which belong to the same class is really huge. To narrow the results further, we can click on the “show filter tab”.
- We can then select drugs and drug classes and go under the antidiabetic drug class to then find acarbose and see if there is any mention of transaminase in its labels. [CLICK] Indeed we see that there are 4 results found with acarbose. So we just need to select this and click “apply filter”.
- So here we can see the 4 results. Now if you look at the lines closely, it looks like it is the same result mentioned 4 times. In fact, [CLICK], the results pertain to different labels which can be really useful because you may want to know how has the data changed since the drug was approved. To give you an example of how easy it is from here to go into PharmaPendium and find the data, simply click on the link which is at the top of each result, so for example we would click right right where the top red box is in the result list…
- And then here we would land on the page from where the data was extracted from. And here you can get to the information you are looking for without having to waste a lot of time searching for information. In PharmaPendium, none of the content is altered at all, it is the original content so you can be rest assured that you are getting all of the correct information. Keepign everything in its original form was actually a requirement from the FDA.
- (Read off slide) Now I will leave you with one more observation.
- In order to show the depth and breadth of information, we will choose a drug that was approved in 1995 just so we can show you how examples of much information you can access when having both PP and Embase as there is a lot of rich data that we can extract out.
- Now let’s go back again to this result page where we had searched acarbose and then filtered by adverse drug reaction and liver toxicity. If we scroll down the results….
- We will come to this result, #13, called “Hepatotoxicity and hepatic metabolism of available drugs: current problems and possible solutions in preclinical stages” which looks like a really interesting article since it talks about drugs linked to having fatal hepatotoxicity. Now from the abstract and title alone, it is not completely clear if this article is directly relevant to acarbose. However…
- If we click on the index terms, we can see acarbose is mentioned in the drug index terms hence it is an article that can be of relevance to the particular end user. Remember our scenario again, that we are interested in finding post-marketing information on adverse events related to liver toxicity for acarbose. This article would not have been picked up by PubMed, hence critical information would have been lost during our pharmacovigilance monitoring. Now we don’t have a subscription to this article
- Here is another example of an article called “Prediction of severe adverse drug reactions using pharmacogenetic biomarkers” which also looks really interesting. This too would have been missed by PubMed, and here since we have access to the article, I can show you what kind of information you could have gotten.
- By looking a little more closely at the abstract, we can see that this article actually focuses on the Japanese demographic, which is information that is often times hard to get.
- This table was found in the article which lists drugs that reported cases of hepatotoxicity in 2008. [CLICK] Acarbose is linked to several of these cases. In addition, you can see that there is mention of numerous other drugs. Which one of these drugs are approved for the treatment of diabetes in the United States and Europe?
- You can go into PharmaPendium and look up the list of [CLICK] antidiabetic drugs and then cross-reference that list to the one in the title. This list is too long… but going through the list we can actually identify additional drugs.
- In fact we see 2 more drugs identified. So where do you go from here? Well you can actually go back into PharmaPendium and now do a comparative adverse event search and see which drug has a better safety profile and then from there try to figure out why.
- So if we go into PharmaPendium, and it is very easy, all we have to is click on the safety data search tab as indicated by the yellow arrow and we will get to this safety data search form. We just need to click on the “add drugs and drug classes” link to add the drugs that we want to compare.
- On the left hand side, [CLICK] this “browse drug” tab will appear from which we can actually find the drugs we want to pick out. Simply click the add button and they will be added to the list [CLICK] displayed here. Then click on “search now”.
- And you will see [CLICK] over 1700 lines of extracted adverse event and toxicity data available for you to compare the safety profiles of each drug and even export so that you can do some more advanced analysis with your team. But till then, you can actually narrow down your search results even further by clicking on [CLICK] “show filter” and facilitate your comparative analysis.
- In this case we can actually choose [CLICK] to see which adverse event we would like to do a comparative search on. We can choose “hepatic and hepatobiliary disorders.
- Within minutes you can find extracted comparative adverse event data like what you can see here. Not only can you get comparative data between drugs but also across species, which is really valuable when you are trying to see how to best design your clinical trial and preclinical studies to avoid seeing adverse events such as these. And by gaining visibility into the dosing used for studies that showed these adverse events, you can then use this information to design better studies which can save an incredible amount of time and money.
- Now if we go back to the “show filters” tab, where we had selected the hepatic and hepatobiliary disorders, you can also look up information on transaminases under [CLICK] liver function analysis. Also very critical extracted information that you gain with just a few clicks. And it is a great way to supplement the insights that you would get from Embase in order to get the comprehensive drug safety picture of pre and post marketing events.
- And last time we had restricted the transaminase search to just the FDA labels. But here when we search the whle document you can see how valuable it is to be able to see at what doses you start to observe elevated aminotransferase events.
- You can also look at preclinical studies…
- And now see what were the preclinical studies that observed this event and understand what were the warning signs that these observations were going to translate to the clinic.
- (Read off slide) Now I will leave you with one more observation.
- In order to show the depth and breadth of information, we will choose a drug that was approved in 1995 just so we can show you how examples of much information you can access when having both PP and Embase as there is a lot of rich data that we can extract out.
- Now let’s picture a scenario where you are a scientist in the year 2010. You are monitoring post-marketing adverse events for acarbose because you are developing a drug in the same drug class and you want to know if there has been any major adverse events since the last approved label, which in this case, would be in 2008.This is where Embase can help give you access to studies which have published additional clinical trials related to this topic.
- We looked at another article from our 194 article subset which actually [click] mentions how treatment with acarbose actually resulted in cases of potentially fatal hepatotoxicity. Now this was not mentioned at all in the 2008 label.
- If we now go in PP and look at the drug acarbose, where you can have links to the approval packages, pharmacokinetic data and adverse and toxicity events, and we look under post marketing [CLICK] events….
- You can see all of the adverse event reporting. Once again by clicking [CLICK] on the show filter tab…
- You can actually look for hepatic failures and get a more comprehensive view of all of the reports which have been made for hepatic failures.
- When you select for hepatic failures you will see [CLICK] we get 17 reports. By clicking on those 17 reports….
- We can actually get a view of what were the concomitant drugs, secondary suspect drugs, and interacting drugs which could have also been identified as playing a role in the adverse events listed. Again, this can provide really key insights for pharmacovigilance monitoring. As you can see, many of the adverse events led to death. One can then go back in Embase and further search for these events and get more clarity as to why these events took place.
- So when looking at the 2008 label, you can see that nothing is mentioned about any fatal adverse events being reported…despite what we have seen.
- But in the 2011 label, [CLICK] it does mention fatal outcomes, however it took 3 years to show up on the label. Hence you don’t want to wait 3 years before you find out that this drug has fatal adverse events assoicated with it, especially if you are developing a drug which belongs to the same drug class or has the same target.
- (Read off slide) Now I will leave you with one more observation.
- In order to show the depth and breadth of information, we will choose a drug that was approved in 1995 just so we can show you how examples of much information you can access when having both PP and Embase as there is a lot of rich data that we can extract out.
- # 32 prediabetes: to treat or not to treat
- In fact if you look in PP, you can see studies which were done. When we do a “discontinuation” search in the acarbose drug approval package, we can retrieve information on what are some potential reasons for discontinuation of the drug. [CLICK] And we can see that the reason why patients discontinued the drug was largely due to gastrointestinal events.
- (Read off slide) This is actually what we are going to answer next with our final embase plus pharmapendium example.
- So we can actually show you an example of how to answer that last question by actually giving another example for the last use case related to patient compliance.
- So let’s go back and see the 194 results again in Embase and let’s [CLICK] open up the drug filter. Here we can immediately see that after acarbose, metformin is the next frequent drug mentioned. It might be interesting to see if this is a hint of some kind of combination drug therapy.
- So [CLICK] we can go under the Advanced search tab and type acarbose and metformin [CLICK] in the search bar..
- We will come across this interesting 2010 article where they do mention studies [CLICK] of both acarbose and metformin studies and how the combination of both is superior than just the monotherapy with metformin alone. From here, by looking at PharmaPendium we actually know that the combination of acarbose and meformin is nt actually approved yet by the FDA or EMEA. We can then ask, was this ever tested before the approval of acarbose? And in fact the answer is yes and you can find that information very easily in PharmaPendium.
- Now here I had actually came across the information on acarbose and metformin accidentally by typing in “dosing concerns” in the FDA approval package search bar [CLICK]. However you can easily type in metformin and come to the same pages as well. Now I would like to point your attention to a few things on this slide. First [CLICK] you can see that it clearly states that though acarose was approved in 1995 for treatment of type 2 diabetes as noth a monotherapy and in combination with study with acarbose sulfonylureas, the combination with metformin was not approved. [CLICK] Here you can also see that this was a study was felt to be inadequate because the combination of both acarbose and metformin potentiated the gastrointestinal events which could lead to low patient compliance. Hence if you were to carry out drug combination studies, you may want to carefully carry out your dose response studies in order to minimize the gastrointestinal adverse events.
- Here you also see a clinical study in the states.
- As we scroll down you can see the same concern that was found in the Canadian study, that the combination of both may lead to an acceptably high rate of gastrointestinal complaints. [CLICK] So how can we optimize studies moving forward. Is there any hint that we can find in the approval package that can provide us some guidance?
- Well if we scroll further down into the package, we can see some interesting information that is provided. One solution is to preselect patients who are already on the metformin therapy AND who are tolerant to the gastrointestinal effects and then put those patients on the acarbose plus metformin therapy to see what happens. And this is an example of some of the really good pieces of information that are in these approval packages.
- (Read off slide) Now I will leave you with one more observation.
- Overall, as you can see with this one drug example how useful and critical it is to have Embase and PP together in order to get that comprehensive view of drug safety from preclinical and clinical studies, to post-marketing reports. I really encourage you to let us know if you would like to be contacted to receive further information on these products to see how we can best serve your needs.