Good morning I'm going to talk to you about RxNorm and DailyMed which are two different types of information having to do with drugs. I'm going to start off talking about RxNorm because this is historically where I started.
First let me tell you what RxNorm is. RxNorm is a vocabulary which was built to support interoperability between various kinds of drug naming systems. Some of the drug names -- most of them used in the United States are proprietary and used with pharmacy knowledge bases to provide information about pricing about drug interactions, dosage adjustment. RxNorm was conceived of as part of the Unified Medical Language System that Jan Willis is going to talk about, I believe after me. 

The whole impetus of this project arose in my attending HL7 meetings, which is a standards development organization about messaging and medicine, and one of the problems that they were talking about was: how do we talk between these proprietary drug naming systems.  If we send a message in one naming system, the people who are using a different naming system at the other end don't know what we're talking about. After a fair amount of discussion, as often happens in standards development organizations, we came to the realization the level of discourse that we needed to talk about was a clinical drug. A clinical drug was defined as an ingredient with a strength or a form or both. So a Valium tablet would be a clinical drug, or a 5 milligram Valium would be a clinical drug, or a Valium 5 mg tablet would be a clinical drug. Now this gives you an example of kinds of ways one clinical drug was named in different systems. Given the way the UMLS is built, it became very difficult for a system to recognize that we were talking about the same thing. Each of these is a little bit different if you look at them so that  in the UMLS, we have lots of unrecognized synonymy between these various types of clinical drugs.  One way that people got around this problem is by the use of NDC codes. NDC codes are assigned by the Food and Drug Administration, administered by the Food and Drug Administration but they represent not only product (what we could call the clinical drug) but also the package size so Valium 5-milligram 25 tablet vial would be a different NDC code than a 50 tablet vial. Another thing about this is no source of NDC codes is absolutely complete or accurate. Some of these proprietary knowledge base vendors have six pharmacists and all they do is they sit around and talk to the manufacturers to know which NDC codes they are assigning. They are still inaccurate. As an example, here is -- are all the NDC codes associated with a single clinical drug  a propranolol 10-milligram tablet. Now, if youre doing something like trying to maintain a knowledge base, you cant maintain a knowledge base at just the NDC level for just this reason. You need to have some level of granularity which is not that specific in order to maintain this. So we developed this model of what a clinical drug was and said that we were going to name things in a specialized normalized way  a standardized way of creating a name, with a standard way of expressing strengths, standard set of forms, standard set of rules about how we decide if two strengths are the same or different, with establishing relationships between each of these concepts and other concepts.  So at the top left we had -- you can't see, you see the model there which is a nice little graph of relationships and the third one down on the far right is for Zyrtec 5 mg oral tablet. And if you follow the set of relationships, up on the top left youll see that this relates to cetirizine as an ingredient. 

Having had this set of  these sets of rules, what we've done is taken these source vocabularies, the proprietary ones, the ones like First Databank, which has a 60% market share in the United States, Multum, Micromedex and Gold Standard the VA has their own system, SnoMed-CT has some drug names in it. Weve also obtained drug names from two different sources from the FDA. One is their listing of NDC codes and the other is the DailyMed. Each of these -- we take the name of the clinical drug from that source and we create the standardized name associated with that drug and then, because we assert that when the two drugs have the same standardized name, they mean the same thing. We can establish synonymy in that way. Where we are now is we have covered 99% of the prescription drugs in the United States. We're producing an edition on a monthly basis and we have, if you go to the MeSH website or the website here, you can connect to documentation about RxNorm. Also there is a browser available where you can look at each the graphs for any of the medications that you would like to see. Now what makes this a little bit different from the rest of the UMLS is that, in the rest of the UMLS, we do not, as a rule, create a name. We just use the names of the source vocabularies. Here we are creating a name. Also, the UMLS is limited to three or four releases in a year. If youre going to worry about clinical drugs, you have to release much more often than that.  At the present time we have a monthly release.  Soon we're going to get to the point of having a weekly update release. Also, we have defined a very narrow region of the world of biomedicine that we're going to be concerned about. We're only concerned about clinical drugs. Were not concerned about allergy classes, were not concerned about diseases, were not concerned about taxonomies of organisms.  Lots of other things that are important in biomedicine are not involved in the RxNorm model. 

Now I mentioned that DailyMed was becoming a source for RxNorm.  Now I have to explain what DailyMed is.  DailyMed is based on a structured product label. Its the FDA approved information for -- largely for prescribers and dispensers, but occasionally they have information for patients as well. Now, the old method of distributing these -- because the Food and Drug Administration has the ability to regulate commerce and drugs  well, you have to ship this information with a drug.  And so I'm sure that you've all experienced the phenomenon that youve gone to the pharmacy, and you come home with a package, and you open it up, and you find this little piece of paper, and as you unfold you get your magnifying glass because it's in very small print and you read it. Now, if that information from the manufacturer changed between the time they printed this and it got up to the pharmacy and you bought it, the FDA has changed it and approved what it said, this has not been updated. Ii is the information that was printed at the time it was manufactured. And, of course, if you are a prescriber, how often do you see these labels? Well,I see the labels on my medications, but in general, you do not. 

The FDA decided a few years ago that they were going to try to become an electronic agency. One of the things that they're requiring is that they're requiring an electronic submission of this label in a structured format, and the agreement that we have is that once they have reviewed this label and approved it they send it to us electronically. Then we put it up on a website which is compliant for individuals who have disabilities. Individuals can download a single label or all of the labels that are currently available and of course, the instant -- the day we receive an updated label, we replace the old one with a new update. 

In addition, because we have this label we're going to put up we can also make links available to other part -- to other resources that are important. PubMed, MedlinePlus, clinicaltrials.gov. SIS has a very interesting database about presence of drugs in breast milk that can be very an important concern and we also have a link to the FDA website where you can report adverse events. With using now these labels and information how a drug is supplied in a label as a source of names RxNorm we can link the names and codes to this label. 

We have a number of functions, too.  We do not yet have an archive of old labels. That is a feature to come. It's on the drawing board, just a matter of time and resources when we have that available. We also have a really simple syndication subscription service where individuals can register to be notified of changes in the DailyMed or specific labels. 

Now I'm going to show you what the DailyMed website looks light. Today we have 2700 labels. I estimate there's going to be 5 to 6000 labels when the FDA is finished approving the labels and submitting them to us. This is how many they have seen and approved electronically. As a demo -- I'll like to look at this Ticlid that is common in individuals for prevention of stroke. The first thing you see, on the left is options for downloading, the additional link site. In the center is the label. Now because this label comes electronic in a -- electronic in a structure put up tabs for the major pieces of it. When I was teaching medicine people frequently want to know what size do these pills come in? What they really wanted was the how supplied. And so, of course, we have a little section here for how supplied. They're white oval film coated tablets. The FDA requires that every solid dose form of a medication have a unique appearance. Sometimes it's just an imprint code or sometimes it's the color for size and so forth. One of the important things is that this medication has what is known as a black box warning. The way that black box warning was dealt with in the past, when a manufacturer on a medication they sent out to all the 600,000 physicians practicing a Dear Doctor letter. Having been there I can tell you that you get one of these a month and you look at it and say very interesting. But the next time you see somebody taking that medication you don't remember anything about that. Now, it's right there in front of you every time you want to look.   It happens that this medication is a somewhat tricky one. It has patient package insert and you can select that and see what information there is for the patient. There are also about a hundred or so medication guides which are similar to package inserts that the FDA is requesting the pharmaceutical manufacturers to produce and when they have a sufficient number of those, we can identify them, we'll have those available as a separate list as well. 

Now you can see on the left the links that we can go to. We can find a clinical trials involving this drug.  -- last thing I want to do is answer a survey now. -- So we find that there are three studies that are -- two of which are recruiting and clinical trials.gov. Now if I want to search PubMed I can go into articles and click on adverse affects and click on articles that are submitted in PubMed adverse affects. I think I told you we were going to have the RxNorm codes and names linked. There are RX names, if you click you can see the names and codes for this particular medication. It's only supplied in one size, the 250-milligram tablet. 

Is there going to be an opportunity to llink from PubMed to DailyMed? That's not up to me. I can suggest it but, I think it would be helpful if other people suggested it. 

[INAUDIBLE]
Right. One of which is if you look at it is Ticlid 250 oral tablet. That's the branded name. And Ticlopidine 250 mg oral tablet is the generic name.  So we have both the generic and the branded name.

[INAUDIBLE]
I will not say number one tends to be the branded name and number two is the generic name. You understand that a label might have 4 or 5 different sizes of medications involved. You look at the label for Synthroid for example. It comes in about seven different strength. It could be a long list. There are a number of other issues. And also, if I say amoxicillin 250-milligram tablet there might be five labels that apply to amoxicillin 250 milligram tablet. So th linking from the names to the labels is not a unique link. It can be one to many. 

I'm sorry I can't hear you. >> 

Is there a link from MedlinePlus to DailyMed? Yes there is currently a link. And of course, we have a link here from DailyMed to MedlinePlus. I didn't demonstrate that. I can show you where that occurs. 

Was there any thought of indicating which is generic or which is the brand? I've not really thought about that. What I have been concentrating on is getting those names and codes in on the DailyMed site and created out of the DailyMed site in RxNorm. I'll certainly think about that as a potentially worthwhile suggestion. 

Yes, ma'am. >> [ INAUDIBLE ] 
What we put up is the label FDA approved information. It's what the FDA considers as established by good evidence or needs to be told to individuals for health reasons. The other sources are, as you saw, MedlinePlus and PubMed.  In that case you have to look at them and read them appropriately. The way we deal with conflicts is really -- I feel like I'm a librarian. This is what the information says. This is who said it. That's all I'm going to say. You know? I'm not going to -- part of the reason I have the links there is sometimes what the pharmaceutical manufactures get the FDA to approve, but what you really want to look at the literature about that. That's a different story. I think that there's recent legislation requiring that the NLM, I think it says NLM, host information about the results of clinical trials of which case that will be more and more interesting.   When you think about things like Vioxx where this information wasavailable in the clinical trial results whbutich was not made publicly available at the time. Any other questions? What? 

Are there generics in DailyMed? 

Yes there are. Generic drugs are required to have an approved label by the FDA. There are generic drugs in DailyMed as well as the branded.

 Now comes the very important thing. Who didn't get a ticket for the drawing.