**Transcript of Cyberseminar**

**HERC Health Economics Seminar**

**New Guidelines for Cost-effectiveness Models: A Report of the ISPOR-SMDM Modeling Good Research Practices Task**

**Presenter:  Karen Kuntz, ScD**

**April 17, 2013**

**New Guidelines for Cost-effectiveness Models: A Report of the ISPOR-SMDM Modeling Good Research Practices Task**

**April 17, 2013**

*This is an unedited transcript of this session. As such, it may contain omissions or errors due to sound quality or misinterpretation. For clarification or verification of any points in the transcript, please refer to the audio version posted at http://www.hsrd.research.va.gov/cyberseminars/catalog-archive.cfm or contact:**herc@va.gov*

Presenter:I am really pleased to introduce today’s speaker, I wanted to spend just about 30 seconds saying why I think today’s talk is so important. Modeling is really an essential tool for cost effectiveness analysis that is because we cannot test all possible combinations of care that we are interested in, and although we are interested in the payoffs over patient’s lifetime, we cannot follow patients until the end of their life. So a model is inevitable, that said the people who make healthcare decisions are often very skeptical of models and so it is up to us who develop them to make them accurate and transparent and to have some objective standard by which we can judge how good the models are. And so that is really where today’s’ talk is about, I am really pleased that Dr. Karen Kuntz is able to make this presentation today, she is part of the taskforce of the two organizations that developed good practices for decision modeling that were released last year. Dr. Kuntz’ professor in the school of public health at the university of minnesota where she has done a lot of work on evaluating cancer, especially colorectal cancer screening important work that has been used by the US Preventive Services Taskforce which really sets the standards for US Healthcare. She was Co-Chair of this taskforce and she has her masters and doctorate in bio statistics from Harvard School of Public Health, Dr. Kuntz.

Dr. Kuntz:Thank you, I am excited to be here to present this work, I want to acknowledge the taskforce leads. In addition to myself Jaime Caro, Uwe Siebert and Andrew Briggs who were the four taskforce leads and I guess we are going to start with a couple of polls of the audience so I think I send it back to Heidi and so the first question that I am asking, okay do I need to click okay there. Okay the first question is are you familiar with decision modeling using cost effectiveness analysis, the first option is yes I develop them, second is yes I participated in projects with models, the third is I have read studies that used them and the fourth option is no.

Heidi:And we will give them just a couple more seconds, give me just a couple seconds to get the answers in and then I will put the results up for you.

Dr. Kuntz: So it looks like twenty three percent have developed them, sixteen participated in project, forty one read about them and twenty percent not familiar so a nice distribution. And then there is the second poll is for those of you who are familiar with them, what sort of types of models have you developed and I guess pick the one that applies the best. Decision trees, cohort mockup models, and individual levels markup models or might be Markov micro simulation models, discrete event simulation models or other? That is a little over half, fifty six percent was decision trees, twenty two percent cohort markup models, ten percent individual level, four percent discrete event simulation, eight percent other so that gives me a nice sense of the audience thank you and then I will give controls back here. So just a little bit of background of this taskforce, the international society for pharmacoeconomics and outcomes research has traditionally had a very good infrastructure for developing best practices papers. They did a 2003 paper of best practices and modeling that was published in *Value in Health*, Note Weinstein was the lead author. *The Society for Medical Decision* making has been interested in this type of work but has only really developed at this time; in 2010, they develop one paper, kind of a best practices paper on diaster modeling. And so in 2010 when ISPOR decided to update the 2003 article, they invited SMDM to be involved so it is really nice to have the two societies be involved with this set or series of papers.

There were six working groups developed on six topics so in 2003, they had one paper and in this effort, there were six different working groups working separately and we combined forces and worked together, we had in person meetings where we had input into all of the papers. So the first was conceptual modeling working group and the authors are shown here. There are three papers on three different types of models so one paper on state transition models, a second paper on discrete event simulation models which is a type of modeling from engineering but becoming more and more used in the field and especially in industry. Dynamic transition modeling and then the last two papers dealt with parameter uncertainty and estimation and the last model transparency and validation. So seven papers were published from this work, one from each working group and then an overall paper, all seven papers were published simultaneously in two different journals. Medical Decision Making is the journal associated with *The Society for Medical Decision Making*and *Value in Health* which is the journal associated with ISPOR were published in the September 2012 issue and so they are available. 

All the papers went under external extensive review, all of them prior to even being submitted have external reviewers from broad representation of the societies. They were approved by the journal editors prior to submission. All authors had to document responses to comments, even prior to submitting to the journal and then once they were submitted to the journal, they had to undergo the traditional review process. They were also posted to members of the societies and members were able to review and comment on the papers. So I am going to go through each of the papers and just touch on the key recommendations. So this is the conceptual framework of the conceptual modeling paper and the idea is that you can start with reality which is this blob and note there are lots of nuances and things and we want to turn this into a workable problem. So how do we conceptualize the process? How do you think about the disease, the decision problem, intervention affects the costs associated with disease and the intervention etc and that later gets conceptualized into a modeling type but there were some suggestions about how to go about thinking about what model type you may need for a particular mocked problem. Here the parameter estimation and uncertainty paper dealt with how to take data sources and parameterize the models and there was a lot of discussion about stakeholders and users and where their role is in this conceptual framework.

So some of the recommendations is a set of models should collaborate and consult to insure the model adequately addresses the deficient problems in disease in question that is a good representation of reality in consultation should be done with experts in the fields in addition to stakeholders. Those people that will ultimately be the model users, the users of the model results. There should be a clear written statement of the decision problem adjusted in scope. The conceptual structure of the model should be linked to the problem and not based on data availability, not necessarily based on data availability. The model structure should be used to identity key uncertainties in the model where sensitivity analysis should inform the impact of structural choices. I think this is again what Paul mentioned about transparency models always deemed you to swap boxes, I think it is important to think about the structural, the functions that we make and how we might as we are building models think about doing structural sensitivity analysis under assumptions. And then the third recommendation is follow an explicit process to convert the conceptualization into an appropriate model structure. So the use of influenced diagrams, concept mapping, expert consultations, just some language in there about how to actually communicate with the final model users, stakeholders in terms of helping them understand the structural flow of the decision.

And then lastly simplicity is desirable, this was a large area of discussion and debate among the taskforce. Do you go for a very complicated model and try to model every little thing or do you really try to capture what is most important and keep the model as simple as possible and the ultimate decision was to with simplicity of aid in transparency ease of validation in description etc? But it needs to be sufficiently complex to answer the questions and needs to maintain face validity so that sort of tension in terms of how complicated the model needs to get. This is just an outline of the different types of models, if you just need a simple non-dynamic. Structure of decision tree works fine when the disease or deficient problem is based on events that happen over time, states of health. A state transition model is more appropriate if there are interactions or resource constraints that you want to incorporate the needs something like a discrete event simulation model or an agent based model. All modeling studies should include an assessment of uncertainty and I will get to more detailed recommendations from the uncertainty chapter. The role of the decision maker should be considered, always thinking about who the stakeholders is, the model users are. 

There was a lot of discussion about terminology and how terminology varies and there is some effort given to really trying to think about what terminology to use for what things and so that is included in the papers. One wants to identify and incorporate all relevant evidence so as opposed to cherry picking of that source. So when you are trying to estimate a parameter in your model, do you pick one study that gives you that information or do you try to really incorporate all the evidenced that is out there even if it is a mix of quality of the evidence. So the recommendation here was to as much as possible use all the relevant evidence. I am not sure that anyone is suggesting that every single parameter in a model needs to be based on a thorough systematic review of the literature but secure evidence to incorporate all relevant evidence in forming each parameter. And then whether employing a deterministic sensitivity analysis or probabilistic sensitivity analysis on the link to the underlying evidence base should be clear. And so there are results thinking about the different terms that are used and they have a preferred term, first order uncertainty, parameter uncertainty, homogeneity and structural uncertainty and then talked about the concepts and the other terms that are used. So variability might be used and many times, it should be used in the same sense meaning first order uncertainty if you are running a hypothetical cohort through a model, where they had outcomes distribute at the end is a concept of variability as opposed to uncertainty. Which is if you have a parameter in your model that describes the probability of dying due to a surgical procedure, there is some uncertainty about that actual number just based on sampling uncertainty based on this study size for example. So those variability uncertainty and homogeneity were hopefully well described and the differences among them clearer and everything was actually tied to an analogist concept in regression analysis.

So the recommendations from the parameter estimation of uncertainty paper, a few of the key ones are here, first was this notion that a lot of times sensitivity analysis reads gives you somewhat arbitrary ranges when we vary an input parameters, the sensitivity analysis is when you take a parameter and you carry it within a range and you see what impact that has on the results, how the results range. And so while a completely arbitrary analysis can be used to measure sensitivity, it should not be used to represent uncertainty so they made this distinction between looking at uncertainties versus just taking an arbitrary range of the model parameter. So consider using commonly adopted standards from statistics such as ninety five percent confidence intervals to base the uncertainty analysis on. When there is very little information, analysts should adopt a conservative approach in choosing when doing a probabilistic analysis we put distributions on all of our unknown parameters and the task force recommended in favor of continuos distributions that provide realistic portrayals of uncertainty. And in other words, they were not favoring something like a triangular distribution, which is used sometimes, and they recommend considering correlations among parameters. But I do not think it went any farther than that that it was necessary to incorporate correlation and that has been an area of debate and concern about probabilistic analysis is the lack of correlation among parameters.

So I should note it earlier the task force is really about modeling and not about cost effectiveness per say so this chapter even though it did cover cost effectiveness analysis a bit, it really did not get into the issue of uncertainty on costs. And I think that does raise a challenge in terms of when you put in distributions on cost with the best way to represent uncertainty and cost. This notion of structural uncertainty came up in a lot of different working groups, so where uncertainties and I have mentioned it before, so where uncertainties and structural assumptions were identified in the process and conceptualized in building the model those assumptions should be tested in a sensitivity analysis. And it can be quite challenging to post talk, changer your model completely to look at structural assumption so the notion is that as you are building the model, one should consider where there may be some key structural assumptions if they can setup at the beginning to allow a structural assumption to be evaluated. 

For reporting uncertainty, uncertainty analysis can be deterministic or probabilistic so they did not come down for example on one side saying that everyone must do a probabilistic analysis. That has been an area of debate over the years in terms of whether that is considered best practice too that everyone should definitely need to have a probabilistic analysis, they did not come down on that. So in additional assumptions or parameter values are introduced for purposes of uncertainty analysis, use values should be disclosed and justified. When model calibration is used to derive parameters uncertainty around an uncalibrated value should also be reported. Calibration is a technique that is used for estimating parameters, so sometimes we do not have direct evidence of a probability in our model so we have data that we can run our model and the model output would be able to be matched to the data. So we want to estimate a parameter in the model such that the model output matches the data we have what we would call a target data. So the uncertainty around those calibrated values is what is mentioned here. 

And then the purpose of the probabilistic sensitivity analysis is to guide decisions about acquisition of information to reduce uncertainty and results should be presented in terms of expected value of information. So instead of coming down and saying all the cost effectiveness analyses should include a probabilistic sensitivity analysis, they are saying if you do a probabilistic sensitivity analysis the real reason to do it is to do an expected value of information analysis. And that is essentially saying if we could reduce the uncertainty we have in our model and the way we reduce it is to collect more information to do more studies, how much would that be worth to us to actually be able to make better decisions with more certainty the outcomes that might happen. So I do not know if you are familiar with expected values information but they really came down on that that was the real value of probabilistic sensitivity analysis, taking it to a value of information framework. And then the last comment ahs to do with when you have multiple comparisons that when you are doing that cost effectiveness acceptability curve that they should be plotted on the same graph. 

Very briefly, on dynamic transmission models, they are really used when you are modeling the risk of infection and are transmitted across individuals so risk of infection is dependent on the number of infectious agents in the population. So an infection that you might get from a tick for example is not something that you need to worry about modeling a dynamic transmission model of infections that you might get from being exposed to someone else in terms of coughing or sexual intercourse or IV drug use would be the setting where you are transmitting from person to person. And the infectious disease model or dynamic transmission model you capture the infectiousness and that would be appropriate if you were looking at the cost effectiveness of a certain vaccine, a dynamic transmission model may be appropriate. There are other models called Agent Based Models that are similar to a dynamic model that interacts among individuals in a simulated universe if you will. You do not see agent-based models as much in cost effectiveness analysis, I would say the most commonly used model that you see are state transition models and basic deficiency models. So the choice between a cohort and an individual simulation model is just when you are running the model whether you are running a group of individuals through simultaneously or if you are running one person through at a time. And if you are running everyone through individually, you have to; it is very difficult to capture history and to make future risk a function of where they have been in the past. When you run individuals through one at a time, you can actually allow the future risk to be a function through where an individual has been in the past, how many heart attacks they have had in the past or how long they have had infection or anything that matters. Any past history that matters about future risk and so when you build cohort models we end up in order to represent reality in a realistic way we end up having more and more health states to capture. So that the past history and we end up with something called state explosion where we have so many health states that the model is unmanageable. And so it is a tension between having the manageable number of states or going to individual which is a more complicated model to develop and it takes longer to run but you do not need that many states to develop it. 

So there was some discussion about what is a manageable number of states and can we actually come up with a number and it really is going to be dependent on the actual modeler and what they feel is manageable and not manageable. And lastly, so the validity should not be sacrificed for simplicity, so when you are building a cohort model and you have so many health states describing the problem, you might make some assumptions that may be some past history does not matter. And so the validity discussion came about in terms of you really do not want to sacrifice validity for simplicity meaning you do not want to few health states that do not adequately represent the problem. Specifications of states and transitions should reflect the biological, theoretical understanding of the disease with the condition being modeled. So you do not want any model that you, sort of health service events, you want to have it theoretical, biological, underpins of the disease represented in your model. States need to be homogeneous and that fact that they are homogeneous they need to be understood that they are homogeneous, that everyone that resides in a health state looks like everyone else in terms of both observed and unobserved factors, so they are all at the same risk for example. So for markup models or state transition models as well as the cycle length, that needs to be specified, that needs to be short enough to represent the frequency of events. A clinical event should also be relevant for its intervention under a study. And lastly, parameters relating to the intervention effectiveness derived from observational studies should be correctly controlled for confounding.

So reporting there are some suggestions about how to communicate key structural elements and the assumptions and parameters in using non-technical language and clear figures. How to maybe add intermediate outcomes that can be presented to enhance the understanding and transparency of the results. Sometimes there may be some interest in looking at distributions of the outcomes of interest so thinking about ways of communicating the model and the model result and the model capabilities through different outputs that are separate from the ultimate output that we are interested in that might be quality adjusted life years and life time costs. So very briefly on the DES which is probably not an area that many of you are familiar with and most of it deals with when you want to incorporate constrained resource scenarios. So they had some suggestions about what to do when you are incorporating constrained resource scenarios, it is also used for non constrained resource settings and it is essentially an alternative, it ultimately boils down to being an alternative at individual levels state transition model. And is being used more and by certain people in the non-constrained resource scenario setting and the main difference that are reviewed between an individual level state transition model. Kind of a markup model when you are running one person through at a time versus the discrete simulation model without the constrained resource abilities or the ability to allow interaction is time is continuos versus discrete in the markup study. So this is all related to CES which is probably, I am going to skip through it sorry.

So transparency validation had some interesting discussions, so recommendation here is that every model should have a non technical documentation that should be freely accessible to any interested reader and should describe in non technical terms the type of model, intended application funding sources, structure of the model, inputs, outputs, other components, validation methods, the results limitations, so really not...

[Phone Dialing]

Equations, nothing geeky and technical but really very user friendly and I think a lot of the documentation I have seen, the technical appendices from a model paper tends to be very technical. I am not sure I have a good example of what this would look like, but I think it would be in some ways very desirable because it is often end users who are not technical, who is not familiar with modeling. One of the challenges is to try to get them to understand the model enough to trust it and to know what its capabilities are and to know what they are looking at, and even knowing what they could do if they were to want to use it. So the idea is that would come from a non technical documentation. Secondly every model should have a technical documentation that should be made available at the discretion of the modelers either openly or under agreement that protects intellectual property. This was the point of a lot of debate as to models that are funded by government should be open in general and models that are privately developed do have intellectual property to worry about. And the second bullet here is that the technical documentation should be written in sufficient detail to enable the reader with the necessary expertise to evaluate the model number one but also to potentially reproduce it. So some models are becoming more and more complex and so the idea is that, there would be enough information in the technical documentation to give them enough time so someone would actually reproduce it. 

Modelers should identity parts of the model that cannot be validated because of lack of suitable sources and describe how uncertainty about the parts is addressed. And for multi application models, which are models that are developed to address a lot of different questions within a clinical area, should describe criteria for determining when validation should be repeated and/or expanded. I think these multi application models are always looking for validation opportunities. This paper actually talks about different types of validation, so first it is just face validity which is more just a debugging, is the model doing what you think it is doing in terms of is the structure evidence that problem information that results is it all pass the sniff test if you will. So a lot of that can be demonstrated through doing different debugging exercises and so this should be formally done and should be able to be described. I guess it is sort of kicking the tires of the model to make sure it is doing what you think it is doing. Verification should be described as this non-technical appendix but it is really internal consistency. I guess face validity is just looking at it; verification is more when you are kicking the tires and just showing that it is doing. So if you input something, a survival curve, can you generate or show that the model will generate that curve so just showing that the equations in your models are appropriately being implemented if you will.

The external validation in its purest form is when you take a data source that was not used to estimate your model parameters and run the model and show that it matches verify well to data that is external data source. They do make a distinction between, so that is what they would call independent external validation, they did use this term dependent external validation which is actually where you can use the data source that you did use to estimate some of your parameters and then show that you can validate to those data too. So they did allow for that level of validation in external validation and then partially dependent is just a mix between the two. So I have a final poll which is, I just picked a few of the recommendations and I just wanted to see based on your initial thoughts are there any of these that you would take issue with, not agree or take issue for any reason. And the first one was the notion that when you build a model, the model structure should be linked to the problem and really not based on data availability. The second was the recommendation that model simplicity is desirable. The third one was that varying the inputs in the sensitivity analysis, varying the inputs arbitrarily with a plus or minus fifty percent range does not represent uncertainty. And then the last recommendation is the one the technical documentation should be detailed enough that any knowledgeable reviewer should be able to reproduce the model. So I just thought I would throw those four out and the last option is that you agree with all of them, you do hot take issue with any of those four. That does not mean you do not take issue with others, so I just thought I would get a quick poll from you guys on that.

Heidi:And the responses are coming in, we will just give them a few more seconds to respond here and then I will put the results up.

Dr. Kuntz: So the number one item that one would take issue with is the varying input arbitrarily does not represent uncertainty at eighteen percent. The second at ten percent is that technical documentation should be enough to reproduce the model, and then the other two were eight percent that had to do with the structure link to the problem and model simplicity and then we had fifty six percent agree with all of them. So that is interesting, so I think at this time we can open it up for questions which I think come from Paul.

Heidi:Paul you have muted yourself if you were trying to talk. The mute button is located on your right earpiece if you just need to click it.

Paul:Yes.

Heidi:There you go.

Paul:I muted myself twice, just so I would not talk out of turn. So we did have one question about the acronym for the...

[Disconnected]

Dr. Kuntz: I cannot hear.

Heidi:Yes, Paul has just turned into a little bit of static there.

Paul:Cost effectiveness acceptability.

Dr. Kuntz: Paul, you are going to have to reread that, you turned to static there.

Paul:I am sorry, someone asked about what the acronym CEAC stands for.

Dr. Kuntz:I can actually see that here, it is Cost Effectiveness Acceptability Curve, so that is the plot where on the X axis is willingness to pay, the fifty thousand dollars for quality years of life device. Here the societies wiliness to pay for quality of life here for example and then on the Y-axis is the probability that an intervention is cost effective. And so when you are doing a probabilistic sensitivity analysis you are taking into account all of these uncertainties, you could have a graph that might go from if you are willing to spend nothing for quality years you may have a very low chance of being cost effective in that you are willing to spend more you could maybe have an increasing probability. So these are curves you see in the literature a lot, it is a way of describing results from a probabilistic sensitivity analysis when you have the cost effectiveness. I am personally not crazy about them but I find them sometimes really confusing but such as they are.

Paul:I guess the concept is that the decision maker can see at their own willingness to pay level exactly how statistically significant the findings are.

Dr. Kuntz: Right.

Paul:So do you think there is something that the taskforce left for some later task force to deal with?

Dr. Kuntz: Well yes but let me think of...so one thing I had mentioned was the whole cost, when we are doing sensitivity analysis or when you are trying to represent the uncertainty on cost estimates I think the concept is challenging. I guess it depends on if you get your costs from, say you do a medicare claims analysis and you have some costs, you can get a ninety five percent cofindence around those costs and you could use that to represent your distribution but I do not think it has been really great guidance on how you should do that. I mean you can also get cost units, costs per utilization units and then that is something that you would consider as known if you really had a...I mean cost is really, is that something that is uncertain or is that just a known cost if you are doing it from a payer perspective. You know what they have to pay and maybe the variability really comes from variability and the number of units that a person might need in their lifetime. So the variability is about the utilization and so then you collect information on the utilization and that is where your uncertainty distribution is on utilization and the cost per part is maybe considered known. I think you do get a lot of this plus or minus fifty percent done to represent variability on cost so I think that is an area that could use a little more thought.

Paul:So we also have a question about have there been any efforts to evaluate and compare the performance of different models and what kind of evaluation criteria should we use to do that?

Dr. Kuntz: So I have been involved in something called CISNA, which is Cancer Intervention, and Surveillance Modeling Network, which is an NCI funded consortium of modelers and our focus really has not been on cost effectiveness. So we have done cost effectiveness but within colorectal cancer, there are three modeling teams so there are three independently developed micro simulation models and so we have done a lot of work trying to understand differences in our models. There is a lot of calibration involved and underlying disease processes, adenomas to prescriptions clinical cancer and so we have key difference in terms of how long it takes for an adenoma to become cancer for example. And we have done what we have coined the term comparative modeling where we use two or three different models to address the same question. And so that is kind of a structural sensitivity analysis in a way since you are varying these simultaneously a lot of these underlying deep model parameters is what we are calling them. The breast cancer group in CISNA has done similar work where they have had actually more models. But we have not compared them to the extent where we are like this one is better than this one, and I guess if you did that you would do it on a validation set so right now we are actually trying to validate our models to the one time only sigmoidoscopy trials that have been published recently. And so I guess this one model came closer to the outcome of that trial might indicate that maybe some of the underlying assumptions that one model were better than another. But it might be that it does better to one of the trials but not as good as to another trial. 

So I think you have to avoid saying what one is better than the other, I think you use these validation studies to try to improve and that was one of the points in the transparency paper was that these multipurpose models should always be looking for data to use to further validate their model, to further understand the model. But there has been a discussion around a lot of different work in looking at models and the role of models; I think there was something on the role of models alongside systematic reviews. And when we grade evidence in the goods grading system, reasonable grading systems for evidence that we are comfortable with and so there is this desire to have the same thing for models. So can we have a checklist or a grading system so that we can look at a model and say this is a good model and this is a not so good model and I think that is really difficult to do and almost dangerous to do. Because a model is, I think what we want to do with our models is to make sure they are just useful and if they are really used for decision making, they are not used for inference, they do not really have the same purpose as a clinical study. 

And so if we can bring in the decision maker, the stakeholder and if they are going to be making decisions with the evidence before them and they are doing everything in their head, I think adding a model to that process is only going to allow them to do a better job in making a decision. It is going to take the information, it can be very explicit about how that information is used, how it is processed, you can do sensitivity analysis to really understand what parameters are really driving the decision. What is important, what may not be as important as first you thought, and so I think if you just keep in mind that the goal of a model is to aid in decision making and that you are using the same information that you wold have without the model, you are just incorporating it in a more transparent way. I think it is important to I guess keep that in mind and then the checklist and the model grading becomes less necessary in my view, but that might be the very picture to come up with the grading system.

Paul:Yes, so what you said is that a model can be better than no model, I think that is a point well taken. So we do not have anymore questions, we would be happy to entertain more people on the question field here. I just wonder though just to play the devils advocate on  this little bit, if you are the Australian medicare program, and you make drug choices based on, you require everyone to submit a model along with their drug application. And I understand that some of the models that have been submitted are either the drug manufacturers are not so good and pretty self-serving. Would you not want to have a checklist or something there to...?

Dr. Kuntz: Well yes, and I guess my number one item on the checklist might be who is doing the model because there is confidential issues that come in.

Paul:Did we loose again?

Dr. Kuntz: I lost, can you hear me, and I think I lost the end of your question because you went out. So I heard the beginning about some of the models is not...

Paul:Yes.

Dr. Kuntz: You are out again.

Paul:Yes, no I did not saying anything I was just waiting for you to finish sorry. Susan would it not be valuable for them to have some sort of checklist to say gee, was the model validated, that sort of very basic type stuff, is it transparent.

Dr. Kuntz: Yes, there are checklists out there about certain things but they are very vague and open to interpretation so did the disease represented and then biologically or did they do adequate sensitivity analysis. So there are a lot of things that are left up to judgement, so did they validate and validation is not always possible because there might not be an adequate validation data set available. But I do think if you are Australian and you want to know cost effectiveness to make decisions on your formulary, you do not want the drug companies doing the model. And I am sorry if there are some drug companies on the call, and it is not that the drug company cannot inform, does not have good evidence to put into it, but I think that there should be some level of independence in terms of the initial conceptualization of the model where there is no stake in the gains. So I think that has always been viewed as a problem for, so it does lead to conflict of interest and the statement that oh someone just draws a target and you know where to put the arrow. So that is independence of modeling independence is important at the get go. Outside of that  I think that yes the user of the model needs to be able to at least understand to a certain degree what the model is doing, what are the assumptions, how do the results vary as you vary those key assumptions. If there is something you do not agree with there needs to be specific analysis that shows what happens if. So all those things are important but I think it is hard to externalate, look at three different models that models three different ways and they are all perfectly fine models in terms of how they have represented the disease, how they have incorporated the intervention and they present it in three different ways that are equally okay. So that is the area and as we move forward I think do we want to and can we, are there the right metrics out there to be able to actually grade models.

Paul:So there is one additional question here, someone wanted to know what type of model we would classify the Archimedes model that was developed by Kaiser.

Dr. Kuntz: Good one yes.

Paul:And then...

Dr. Kuntz: I am not sure if you would classify that as anything...

Paul:I am not familiar with that one myself, so.

Dr. Kuntz: It is very biologically based and it is a lot of equations that describe the...so I do not know if it has a simple, it is not a marked up model, I can tell you what it is not. So there might be some portion of a micro simulation but deep biologic..., but the parameters are relationships between A1, what is the diabetes, A1C, sorry I am blanking on this, the measure for diabetes. And to be honest the technical documentation for those models you can only get if you sign away, sign an agreement and then you are allowed to look at that and I have not gone. So what is in the papers published on the Archimedes models are fairly vague but I know people who have gone and signed the agreement and have gone to look at the codes and I think even they had a really hard time deciding what was going on in those models. So the guy that coded them has a physics background and there are a lot of models out there that are not key health models. There are models that have to do with weather and economics and war and so I am not sure it has a category.

Paul:So there is a comment, are you able to hear me?

Dr. Kuntz: Yes.

Paul:Yes, that was a comment that Leslie Wilson pointed out, it is not just the pharmaceutical companies that have a bias, payers and health systems can also have a bias and they said against treatments but presumably also in favor.

Dr. Kuntz: Yes, I agree with that. 

Paul:And I think our view of that is sometimes you have people who are essentially proponents of some new intervention who want to have an evaluation showing that it is good.

Dr. Kuntz: Right.

Paul:And it doers not necessarily need to be the pharmaceutical company.

Dr. Kuntz: Right I agree.

Paul:And then someone else so they asked if there is a checklist fort evaluating models?

Dr. Kuntz: Well probably, I do not know if I would call it a checklist but there is a paper by Phillips, and I cannot remember her first name, it might be Zoey and I think it was 2004 or 2006. I think she has a couple where she goes through and it was through the HTA so she is in UK but it goes through and it has different categories, one is model structure, one is data and one is validation. I think she might ever have items under each of those things about what a model should have. But as I said some of it is very vague and very hard to tell, so that is probably the best one I think that is out there.

Paul:So that is in the journal that is called *Health Technology Assessment*, that is actually put out by I guess NETSCC is it not that puts that.

Dr. Kuntz: Yes, and I could probably send that paper to someone if you can get it out to people who are interested. Would that be helpful if I did...?

Paul:We could post that right?

Dr. Kuntz: Yes.

Paul:We could post the citation and there is a link, I mean that is a freely available journal so we just need to send the link.

Dr. Kuntz: Yes, and if you send me the link I can include that in the archive notice that goes out.

Paul:Well we are past the hour, is that not where we are supposed to draw to a close Heidi?

Heidi:It is so with that we will wrap up today’s cyber seminar, Karen thank you so much for taking the time to prepare and present today, we really appreciate it. We had a great audience, they obviously really enjoyed, and we got a good number of hard questions in there so they definitely appreciated today’s session. For our audience thank you for joining us for today’s session, as you leave the session today you will be prompted with a feedback survey, if you could take a few minutes to fill that out we would very much appreciate it. We definitely do read through all of the feedback that we receive. Our next session in the HERC Economics theories is scheduled for May 22, that is a little different we usually are on the third Wednesday of the month but we will be on the fourth Wednesday in may and John Finney will be presenting *Are Misinterpreted Hospital Level Relationships Between Process Performance Measures and Outcome Undermining Evidence-based Patient Care*. We hope you are able to join us for that, we have sent some registration information out but we will followup with further registration information on that to everyone. Thank you everyone for joining us for today’s HERC health economic seminar and we hope to see you at a future cyber seminar.

Dr. Kuntz: Thank you.

Page 1 of 12

Page 12 of 12