1/12/2012  Randomized Designs for System Level Implementation Trials QUERI Implementation Research Brown, Hendricks

>> Thank you very much and I would like to add my welcome to all of you to the first presentation of 2012 in the VA QUERI implementation research cyberseminar series. Today's presentation addresses a challenge faced by researchers, grant reviewers, journal editors and reviewers, and other stakeholders in implementation research. That is the challenge of sample size, statistical power and research design when evaluating organization level implementation interventions. I am pleased to introduce today's speaker for the topic, Dr. Hendricks Brown of the University of Miami. He has contributed to our field in a number of ways ranging from innovative research methods to imperical research to conceptual and theoretical issues, he holds a number of leadership positions with university and outside. Perhaps of greatest relevance to today's presentation is the role of PI and director to the newly funded NIH center for prevention implementation methodology at the university of Miami. Hendricks thank you for presenting today and I will turn to the platform over to you. 

>> Good. Think you very much for the kind introduction Brian and the opportunity to talk with you folks with the VA system. I am really very pleased to do this one. To me this is a really  important challenge, to get to the point of what are the scientific steps that we need to do for designing the next generation of implementation research? I think this crosses boundaries as much as implementation science itself crosses a number of boundaries. I wanted to move on and if you would note that these slides are numbered in the top third of the slides, there is a slide number. I will follow this one and do these manually, but for people who are following on their own systems you can follow the page numbers. So page number two is our acknowledgments in here, again the center that Brian mentioned here, it's just been funded by the national Institute and drug abuse and also OBSSR, out of the director's office at NIH. And I want to talk about randomized implementation trial and I don't know if that word is standardized but Patty Chamberlain is the director of that and that has been around for about year six, we have been funded in California for this one for multi-dimensional treatment foster care. We are also very closely connected to a NIMH implementation methods center which is run by John Landsverk. We have a number of other projects that I'm PI on as well as a couple that I'll mention: Jeanne Poduska suppported by NIDA and Institue of Educational Research and other areas as well. My co-authors today are people we have been collaborating with and learning as much as we can, Patty Chamberlain, John Landsverk, Lawrence Palinkas, USC; Wei Wang at the University of South Florida; Lisa Saldana, Center for Research to Practice. 

I wanted to get started here with sort of more or less a perspective and I wanted to get your feedback on, and how you'd think about this issue. Here is one perspective on doing randomized trials for the implementation research. I realize that randomized trials have not necessarily been the standard design for running research and implementation research but here is a perspective. Strategies to implement evidence-based practices do necessarily involve organizational, community, or higher-level, system-level interventions. Implementation strategies, for example, is the main thing we have been using as a reference to that. In addition to things like evidence-based practices which might be at the lower level, we are talking about what are the implementation strategies in here? Implementation science is all about understanding those processes. If we want to formally test these implementation strategies, we could at least try to use some scientific principles, the opportunity to randomly assign implementation strategies at large organizational levels. That is a statement in here. 

>> Here is another alternative perspective. Randomized trials do not answer the key implementation questions because they're too rigid, there is too little generalizability, low external validity and the like. Here's the question that I wanted to start with and get your response at the onset here. I will give a statement and I'd like you to see whether or not this is something you agree with much or not at all or somewhat or strongly. "Randomized implementation trials at the organizational level would be scientifically useful for advancing implementation science, if they could be carried out?" I'm not asking people directly whether or not you can carry these things out right now. We will talk about some of those issues. I wanted to get some feedback from people. 

>> So as you can see, 49% of people strongly agree with that statement, also 49% of people somewhat agree and 2% do not agree with that statement at all. I will turn it back over to you now Dr. Brown. 

>> Thank you. It sounds like there is at least some difference of opinion about how important these things are which is I think a very important reflection, not only of your background and your experience in here, but also where the field is. And that is perfectly fine. Let me start with the second issue about the practical concerns about trials at the organization level. You could make arguments that say carrying on randomized trial at the organizational level is generally too expensive and it requires many organizations to achieve sufficient statistical power. Randomizing at the highest levels is unlikely to be supported by those organizations, or communities who are averse to withholding effective interventions, programs, or practices. This is a potential statement that people have made in some regard about this. The conclusion you might draw is that randomized strategies should rarely if ever be used for conducting large-scale implementation evaluations, not necessarily on scientific grounds but certainly on issues around financial, ethical, and other issues. On practical grounds, and if you really do not believe these things should be done on scientific grounds as well, we should rarely if ever use organizational level randomized trials? I want your feedback on that as well. 

>> As you can see, 11% strongly agree with this statement. 45% somewhat agree, 44% do not agree. Thank you to those respondents. 

>> Thank you. It is a very efficient system and I haven't used it before, but I think it does give some reflection of where the field is. There are at least some people who feel strongly, 10 or 11% or so this is really not appropriate in many circumstances at all. There is some debate about the level of this one, some are saying they do not agree, 44%, so there is some possibility. This is where I think the field really is on both of these kinds of questions. Let's go through the outline in here, and I will talk really briefly in an introduction about what methodologies are important to the field of implementation science. 

>> We are talking about what the role is of randomization at large levels. To briefly mention this, the Ce-PIM Center which was developed and then go on to talk about two approaches. What could you do if you could randomized not at high level but at a lower level and when should you do that? The answer is surprisingly clear about when and where you can do that. 

>> The second point is to look at ideas of actually randomizing at these large levels. We've had examples of randomizing at the level of counties for example. And instead of randomizing just on these very large levels, we are randomizing not only location, or place, but also on timing of implementation. We will talk about these things and give you this word 'timecasting' which we think would be useful in here. 

>> An example of the California and now Ohio randomized implementation trial and it is called a roll out a randomized implementation trial. My background in here is from the prevention field and prevention science. A really good and quick summary to give you guidance of where we have been coming in is from the National Academy of Sciences publication that came out in 2009, on  mental and emotional behavior disorder prevention. The summary is there is a lot of interventions are effective. The methodology we used to test for effectiveness on implementation, has really resulted in a lot of this body of knowledge because we've been able to do carefully designed, randomized trials, some of which have taken 15 or 20 years, and long-term outcomes. 

>>The implementation side though, is really unknown. We do not really have a good set of methodologies yet developed that is part of our process. And the center in here on the next page on 11, it was funded specifically for that purpose, to develop new methods. To advance the discovery and the practice of implementation and also the use of these methods in implementation science. We are interested in not only in drug abuse, and HIV and sexual risk behavior prevention but also areas around mental health, depression, suicide,service utilization and programs as well. We are quite interested in talking to a number of you over the next coming years as we think about potential partnerships. 

>> I am going to limit our discussion today to talking about trials. That doesn't mean that there isn't an awful lot of other very important methods around here. I will limit this and not talk about qualitative  or mixed methods or quality improvement designs. I have a reference in here to Landsverk et al. All the references are at the back.

>> The first point I want to make here is about the quantitative designs. There is a limited use of those now in the implementation research field. Here's an example where a survey started out with 2800 studies and only five studies were appropriately designed and/or reported on the range of outcomes so as to influence policy and practice. That is a not a good rate, so one of our objectives is to get more precise about this. In randomized trials, in fact do occur, here is an example of a review that was done by John Landsverk and colleagues on child welfare system and mental health implementation. Nine of 338 programs acutally had a comparison group. That's again not a great rate. Eight of those nine used to randomized trials. Even the Cochrane collaboration which has the EPOC reviews, 57% use randomized trials for evaluating care. 

>> I just looked up on the journal of the implementation science, which I expect everybody is familiar with in here, and Brian is a coeditor of that one and I just counted the numbers of studies. There was about 44/193 research and study protocols, about 25% or so, dealt with cluster or group-based randomized trials. Those were all of the kinds of randomized trials that were in there. Some of those had certainly large numbers of organizations. One trial started off with 40 counties that were randomized in California as a randomized implementation trial, this is the Wang,  et al paper, and this is now been extended to 53 counties. There was also many others that are randomizing at the organizational level but use much smaller numbers. The Boveldt et al. paper had 6 oncology clinics and that is not atypical. The third point is that there's many that randomized at lower levels than the organization itself. I will spend a little bit of time on the strategy in here, one of the papers that was published in implementation sciences was about the design of the trial in Baltimore with 37 first grade classrooms where the organizational level unit here was at the school level and there were 12 elementary schools. 

>> Here is strategy number one that you could do. Given the difficulty and the limited power that you have, if you looked only at randomizing at organizational levels, you could randomized at a level lower than the organization. Here are three places where that could work as a strategy. One, it is essential that it matches the research question. What I call the unit of implementation, the unit keep your looking at that you want to study is actually at the level below the organizational level. For example, Poduska's trial is all about a coaching model for helping improving teachers in delivering an effective classroom management behavior implementation study. It is really the coaching model and so we're looking at how does a coach relate to the individual teacher in here. There are system-level, higher system-level, school, as well as school district, characteristics in there, but for the purposes of this study, that is not going to be the emphasis that you would do in a design when he randomized to the level of the classroom, rather than a level for example, the school. And certainly not at the level of school districts. 

The second thing is is that the amount of leakage of an intervention has to be acceptable. People have been very rigorous about this one, trying to make sure that there is no leakage of the intervention. The data that we have got says you can afford some leakage of the intervention in order to get this one and still get a pretty good design in their. The other point about this is that many of the interventions, such as a coaching intervention, really requires a lot of one-to-one contact and communication. It is not that somebody can easily get this by osmosis even if the next-door neighbor teacher knows about this one and doesn't necessarily mean they would be doing that intervention just because they know about it. It may take a lot more effort. In particular with things like leadership and things like that, in my experience, some of those really do not leak very well or very much, even if those manuals are available in the books are available.

>> Here's an example of a couple, on page 17, lower level implementation strategies. I gave an example here in education in the first column. You can think of this as much more complicated and multiple levels and three, the three might be a useful one to look at in here that you might emphasize. We would for example look at schools using those as what people would call blocking factors, that would be a design where within schools you could randomized classrooms to which intervention or coaching model that you have, and then look at outcomes associated with the child outcomes. And health organizations, you might aim for the clinic but randomize at the level of clinician of within clinic. And then as they implement evidence-based practices. And think for example in social service systems at the agency level, use the service provider who gets supervisor training for example, or group based training which could be a group that you do as well. Or you can think about the governmental systems where county could be a major high level unit or agencies are given differencial money incentives for following up and potentially think about a design like that. And then  use service provider at the level below that.

>> There is another important piece in here. If you are going to randomized a level lower than the organization when does this work? The third requirement is the following: these level II unit classes they should be similar to one another within each of these higher-level groups. For example, the classes within schools should be somewhat similar in order to be able to do that because you're randomly assigning individual classrooms and within those you want to be able to make those comparisons. If those classes are very different from one another you lose statistical power pretty quickly in here. Or the other option is the implementation is very strong. 

 >>Here are results on page 19 of comparisons of statistical power. I have to say that this is the only one that I'm going to talk about in more statistical detail about statistical power which we have been doing a number of projects we have evaluated in here. I do not think it is necessary in this audience to really go through the details of these but if you go back to some of the papers in here, more of the details are available about statistical power. You can ask questions and we can give you some resources about how or what would be useful ways to calculate statistical power using the web-based systems available now. 

>> Anyway, giving the statistical power, this is for two different kinds of designs. One design in here would be a school-based, randomized design where all the classrooms in the school get the same intervention. What you'd have is the school number one would get an intervention, for example, for coaching and everybody at school number two would get a totally different intervention. The dark solid line corresponds to the statistical power to a particular design and you can see that power is about 10%, very low. Statistical power of 10% means it is almost a meaningless design. What it means is that it would be very underpowered if you did a school-based design with that kind of design. On the other hand, the dash lines corresponded  to the statistical power when you do classroom based design, where within schools you randomly assign. The dashed lines separate out for some of these curves substantially. They give very large statistical power under certain circumstances. The X axis corresponds to what is called ability tracking. An American schools they tend to track kids in first grade based on what they think their academic and performance ability is.  You get classrooms where they are very well behaved and academically superior students in one classroom, and then in other ones you get a heterogeneous classes so one class would be filled with mostly behavior problem kids. That is traditionally what happens. If the ability tracking is very small, which is on the left hand of the curve, you'll see huge separations. And that is where the amount of variability of classrooms within those schools are that small and you would get very big advantages with this kind of design. We have used that for many circumstances over time. 

>> The last elipse on the bottom right hand side in here corresponds to the differences and statistical power for school-based design versus the classroom-based design, same numbers of schools and classrooms, when there is a large intervention effect. You can see there is a big separation. That would be nice except for one thing. If it is a really big intervention effect, what is the point in doing it? On page 20 here is an example of a large intervention effect. We'll bring back an old history of epidemiology, John Snow's map of London with cholera death. In 1854 there was about 500 deaths that were occurring in London around this particular area due to cholera. And John Snow went in and actually located where that was. It turned out to be in his mind is source of water so he removed the pump in the next year there was virtually zero deaths. The trouble is we do not have very many Broad Street pumps in our sudies anymore. We have a much smaller effects and so we do need to do things like randomized trials. 

>>So let me move on to the second strategy in here. I'm going to need a little bit of time to motivate this one as we have been motivated given guidance. Here is an example on page 22. We are going to use this idea of rollout designs to try to overcome some of the challenges of small numbers. Here's the first step I wanted to take a look at. Let's suppose that we have two states and we want to do an implementation strategy in one state versus no implementation strategy in another. And suppose we have 100,000 individuals in one state, and 100,000 individuals following  up in another state. Well, if you are looking at comparing the effects of that implementation you're really looking at a sample size of two even though there are 100,000 individuals in here. That is relatively of small importance compared to the number of states that you have. If you flip a coin and decide New York gets one implementation strategy, and Arizona gets another one, there could be a lot of other reasons why you get differences between those two. No matter how many people you measure the individual level. That is the real crux of the problem here. 

>>Small numbers of observations on page 23, means low statistical power, even though you may have large individual sample sizes. The second point was alluding to that in New York versus Arizona, if you have a large degree of organizational differences, it also lowers the power as well. Question is how do you try to overcome that issue? 

>> Here's the idea in here for community level or organizational level implementation. And I give you additional design in here. Starting from the illustration that Hawkins et al did in the American Journal of preventative medicine in 2007. You could treat this as a multiple baseline or interrupted time series design. If you repeated measures over time with the same communities, same organizations, you could get some measures of changes that would occur. Here's an example where there were four communities and there is a specific baseline time theory, then an intervention, and then looking at changes that occur after that time. If you had data like this I think everyone in the room would be fairly convinced that looks like it would be really successful implementation strategy and your outcome would look great. That is a lot of simplification. But let me go to sort of a perspective on what are the different kinds of ways of doing this. You will note that the last example used time specifically to do a change in the design for each of those organizations or communities. 

>>You can think of three kinds of designs. One of them is if you're going to broadcast an intervention or implementation strategy that you are offering it to everybody to see who comes. It is much more of a dissemination idea. You can do what some people call narrowcast, which is a word, and that would be a much more focused one that says these specific communities or organizations are the ones that you'd want to use it to. The other one is what you would call or label time cast. The timing is what you are using to convert and change organizations from a previous step where they are not implementing this to a time when they are implementing that. This is the control that the researcher has in the study. These are called multiple baseline designs in psychology, sometimes  interrupted time series in here. There are repeated measures over time of a community outcome. You introduce an implementation to the community midway through the check whether the community outcome differs before and after the intervention.

>> Here's an example of this one and this one comes from the American Journal of community psychology and it comes from Biglan on changing the way tobacco outlets sell to minors. The idea is to go in here and do a strategy to change the outlets, individual outlets, that are available to the community, and reduce the number of underage sales of tobacco. And what is on the Y axis is the proportion of times at which there was a successful sale to kids without checking the ID. This is part of the design of the study. You can see that this is two communities where looks like a really big, huge change had occurred. The next page, the third one, looks exactly the same way, and all of a sudden the fourth one doesn't look quite so impressive. They had not been for that one, it would probably look quite like the other ones. Here are the problems and limitations of that kind of design. We are building up from that kind of idea of a multiple baseline design. What happens if exogenous factors occur at one of the times of transition? That is the really difficult problem with that kind of design. 

>> In the implementation trial that we were doing in California, we actually had a huge change that occurred midway through that project that had to do with the recession in California. And we were getting the agencies of child welfare, juvenile justice and mental health at the county level to implement a new strategy which was to change the way that foster care children were taking care of. And that problem was a difficult one to do when all of a sudden the counties encountered very difficult financial situations and making changes in here. That is not unheard of in situations of implementation strategies. Greg Ahrens and colleagues  at the UC San Diego is working with colleagues around issues of implementing an HIV prevention program in Mexican cities for sex workers. They had experiences with drug cartels in major cities, there were dozens of bodies left in the areas where some of these clinics were available. Obviously there were huge changes occurring during the process which were outside the scope of the usual experiences. We've had lots of experiences with this one in suicide prevention. One of the projects we had a 10 year anniversary was Kurt Cobain's suicide in the middle of the study and they were elevated suicide attempts among those kids that were in there. The point is, if we did not, we cannot expect to control those exogenous factors. So we need something that will hold in place a design during those times. It seems like randomly assigning the times that they occur is about the only way that I know that you could be able to make that kind of comparison to do it. 

>>So, moving on to the issue of rollout design that do the following system: it divides the available communities into comparable batches, starts measuring outcomes for all communities- or maybe a subset- but certainly the number that  get the intervention early on and some don't. And then randomly assign each comparable batches to when the dissemination begins. That is what we call time casting. The ideas it is a similar design to multiple baseline design but it includes in here randomization of the timing of when the intervention occurs. Then the analysis uses all the communities and all the times in there, it uses communities that change over time so they can service their own controls, and it also uses communities that can be compared at each point in time with each other, some who have the implementation and some who do not, so you can make that direct comparison, even in circumstances where there are some exogenous factors that might be occurring. Here's a picture of it on page 31. This is a quick illustration you take the population, and we're talking about the population in here of, for example, of organizations. And randomly select those into subsets. Construct subsets that are as equivalent as possible. There are five subsets in this case and randomly assign when there is a transition. This is where a dissemination design can work exactly the same way for implementation design. 

>> Then what you'd have in the design, the Os on page 32 represent points in time where's there is no implementation going on, two, an X is where there is a change that occurs in here, so you can see in the first cohort that those randomly selected, start with a couple of baseline values, and then you move into a baseline strategy that you can follow over time and develop a model with growth modeling. 

>>Here are a couple reasons to consider randomized assignment to these kinds of designs. From statistical point of view, we discussed those and there's some papers in here, the clinical trials journal was one reference to this one, we used it for suicide prevention, effectiveness trials and also areas related to implementation trials. They deal with  mostly with statistical percission and power. As well as bias. Randomization should be looked at as a very flexible kind of thing so we're thinking about the tool randomization, used in innovate in different ways. We talk about it at the person level nd also at the place or group level, but you can also randomize the time at which the intervention occurs as well. 

>> Here's a couple of references. Here's the idea. Page 35. It came from an HIV, community-based intervention that was done in the 1980s, or 90s, called the empowerment community invervention and it was targeting young, gay males in terms of their sexual practices. It started with two committees. One was Eugene, Oregon, and Riverside, California. And they had a bright idea of flipping a coin and randomly assigning which one got that intervention first. 

>> They could not have trained both of them at the same time but they decided to randomly assign one of those communities at a time to intervention. And the other one to control. Now if you know those two cities, Riverside and Eugene do not look similar to one another but that is part of the issue of the design. You will never get communities that are perfectly matched anyway or organizations that are perfectly matched. The bright idea with that design was not to start with a simple randomization and stop, but to move that forward and say what we should do is to continue do that with new pairs. So if you randomly assigned which gives the intervention first in each pair repeatedly over time, what you can do is that you can separate out and legitimately measure in year one those who could intervention versus those who get the control. And then in year two you would convert the next group will wait list design and they would get the ntervention. From a community standpoint, they like the advantage because there is nobody who is a complete control group who does not get the intervention. And so therefore you get groups that come in here. 

>> If you look at the comparison of the left hand side of figure 35, the typical way that you would often do organizational interventions is to take one of those, give them the intervention and find a control group. The problem with that design is that it completely confounds your implementation condition with community readiness. And the green and red on the left-hand side are not randomly assigned so you never know over time whether or not it is your intervention or some other characteristics they might have been lucky enough to measure, but more likely you have never measured the particular pieces of community readiness that would be useful in here. 

>> On the right-hand side of the randomly assign those, you do get a design over time they can contribute and advance that overtime. We've used that kind of idea to build up studies and starting very small to very large studies now. 36, 70 high schools for example. So here's the implications of this for community research or organizational research. If you have a large number of units that are available, and you have the opportunity to randomize them when they can do this one, but you cannot do them all at one time, this is the kind of rollout design that might make sense. 

>> The single trial with a small number of communities is virtually always underpowered, but if you think about it sequentially and add on different numbers, small numbers of communities but  randomize which one gets it now over time, you have a legitimate, full, randomized trial. There are a couple of references at the bottom of page 36 that you could look at for looking at getting the statistical power on that. So here is the next point about this one. 

>>A randomized trial is worth doing in implementation? The answer is if you were going to use a classical randomized trial probably wouldn't be good, but the idea of using the roll out designs is a useful way to do it. We've done it in the California trial and along the way we learned about community buy-in. So why would communities be interested in doing these randomized, rollout trials?

 >>First of all it is a fair system. With the flip of a coin when community would get an implementation early on, and the other one would definitely get it, but it would have to be delayed. The payoff for getting it early for community is that they get something that looks like it is an evidence-based kind of program and they can handle legitimate implementation strategies. 

>> The second approach in here, looking at getting something later on, is that you might if you wait a little bit you might get a better intervention. We've used this with effectiveness trials but you can also use this in other areas as well with implementation. Will it be accepted in here? I think we're seeing a couple of examples where that kind of design idea is acceptable and I will give an example of one of these to give you an idea. 

>>This is the California Ohio implementation trial example that Patty Chamberlain is leading it is an evidence-based program for multidimensional treatment foster care. This is for high-end kids who really need a lot of support. And the routine way the counties and child welfare and juvenile justice and mental health deal with his which is to put the kids into group homes which is a tough thing for them to do. No matter how much effort you put in, it is very expensive and they don't get very many services. This is a program to put those high needs kids and really good homes where they really done a great job of training foster parents and provide a team-based support which is really focused on their particular needs. 

>> We started out in California and in some important cases we had to go and extend the trial to Ohio. That is the way these rollout designs work. The implementation strategy is called a community development team model we're  testing it against the standard method. On the left-hand side is what you would think of if you were testing the multidimensional treatment foster care or MTFC so you have a MTFC intervention that you would randomly assigned to certain families and compare that to the control condition. In the background are all the implementation strategies and things that need to happen at the county, agency, clinician, and parent level.

>> And all the other things are in background. That is the effectiveness design. In the implementation design was constant in here is the MTFC intervention what is different and what gets randomized as the counties get randomized to the standard implementation for the county or the community development team model. The task is to see whether or not the CDT method improves the implementation of these programs and ultimately better services for the kids. That is what page 42 indicates. 

>> This is being done in 40 counties in California and what we have been calling the diffusion of innovation kind of research, there  are early adopters and non-early adopters. This is look at the non-early adopting 40 counties after about 10% of the counties have already taken place. Those are the ones that were randomized and we were able to randomize those counties into six equivalent clusters three of which received CDT and three which received the standard implementation and we used measures, the time it takes to adopt, recruit staff, train, and deal with certification of the MTFC program logistics.

>> Page 43 is a picture of how we started out with 40 counties. You can think about those as being blocked into certain areas in here, the CDT and standard settings were the two active interventions and there were 26 remaining counties that were wait listed and the next year we took the 26 waitlisted ones and took the ones who got the CDT versus standard-setting. The remaining 13 waitlisted ones went to that next cohort and we now added a fourth cohort in Ohio to do the exact same kind of thing. A couple of issues on this design. We do not know whether it was going to work. The review committee fortunately believed us enough to say that we could try this one and see how it did. First of all, every county was accepting of this design and was not a big issue. We did have one challenge which I think is one of the things that is going to happen in this design that has to be recognized. Some counties were just not ready to take part when we said ready set go. They said we are not there. 

>> What we did, this is a consort diagram, just to see what we did. We divided these six counties into six clusters and randomly assign those six clusters into cohorts and condition in here. Among the six CDT counties at the beginning, there was a vacancy that occurred from two counties that could not start when we said we would like to start. What we did, we went to the second cohort that was already assigned to the CDT intervention, randomly assigned the invitation process to those and for those who were invited and they accepted it, they were moved into the first cohort so we were able to do that. This did occur in interventional conditions. This was early on. We thought we were able to keep it relatively balanced. But that is the reality. 

>> The second problem which is mentioned, the exogenous factors in this rollout trial, and running randomized trials during a recession is a very difficult thing to have to happen. Had we not used a randomized trial, we would probably have no data that would be relevant to evaluating and comparing those two conditions. But because we did a randomized trial, we did not break that design up and we still had a viable thing going on. Because it took longer than we expected for counties to really get on board and do this implementation process, we went back to the funding agency at NIMH and got additional funding to add 13 counties in the second state and use the exact same inclusion criteria. 

>> Here's the summary. Randomizing implementation trials is not a panacea but I do think it has a place especially at the beginning of the study. And that is a place where we often think maybe that is not a good place to do randomization. But I think that is the place where randomization might give you the most useful bang for the buck, early on, if you can do some randomization. 

>> Some of the early people who did evidence-based medicine, it started off with randomization at the very beginning of the process, we had two circumstances where we could do randomization. One was we could drop down a level and try to randomize at a lower level. We had examples of where you could do that unit of implementation you wanted to study had to be at that lower level to begin with. You had to have some limit of implementation leakage and somewhat comparable lower-level units such as classrooms. 

>> The other alternative in here that I think is a useful, viable means over time is this rollout  implementation trials and I do think it is useful to do this one, even if you do not have a lot of statistical power at the beginning. If you're planning a multiple year study, maybe it will take 10 years to collect the data. But we do not have the luxury to design these huge implementation strategy designs that are going to be done in a small time frame. 

>> From a community standpoint there is a value to do this because everyone gets it, it's a fair assignment in here. From a scientific standpoint there is some advantages of reducing biased and protecting against external events. Again, I would suggest the potential for randomizing at the beginning because if you do not start doing this you will never accumulate the data over time. We do need to do a lot more work on statistical properties in the context of those trials. These are the remaining references to papers. You may want to take a look at these. Thank you very much. I would be happy to hear some questions. 

>>One question regarding your comments on slide 35. Could you explain why the left-hand side method  confounds implementation with community readiness? 

>> Sure. Let's go back to page 35. The tradition in community based studies has been to select or identify a community that is willing to work with you, and then find another comparison community. And if you repeat that process over and over again, what you're doing is, you're getting the one that comes in first for you. And that may differ in subtle ways or measurable ways from the other community. 

>> Another example that somebody tried to do at one time, there was a review committee where they want to do a study in the Bronx. And they created this group later on that they called the Pseudo-Bronx as a comparison group, they the did not get funded and the rationale was that there really is no Pseudo-Bronx. The idea was that if you had pairs coming in as communities, Eugene and Riverside, and said look we know you're different, but what we want to do is find a way to have you measured. You flip a coin to see who gets intervention first. In year one we have both of you measured and one of you will get intervention and one will not and so that we can make a legitimate comparison. And in year two the other group got the intervention. So in time the radmonization here made the readiness and other potential issues will balance out. 

>> Next question, I should mention there are a number of questions coming in and we are not likely have time for all of them. With time permitting, we'll have an answer by e-mail. In the timecaps Design how do you deal with the group that doesn't have a stable baseline when it is their turn to get intervention? 

>> That is a good question. I think that is part of the process of understanding the natural variations. From epidemiologic standpoint, I would say here is a population of communities or organizations. Some of them are going to be stable and some of them are not. And that is usually the process. That is part of the process of the natural evolution of these interventions. Those who are unstable I'd rather make sure to get randomized to ones in both implementation conditions. That would be something that I would try to analyze within the analysis itself with growth models. Putting in a model of baseline variability plus location and change during the implementation process, and what it is after in the sustainability time period. 

>> The next question is a multipart question. Is the stepped wedge RCT another term for your rollout RCT and how should one determine time period between additional rollouts and how does this affect the analysis? Does it have anything to do with the time it takes for the intervention to be fully implementated or is that an independent issue? What are the implications of a larger number of rollouts with a smaller number of organizations in each wave versus a smaller number of rollouts with a larger number of organizations per rollout? 

>> Great questions. The stepped wedge designed is essentially the same as what we are talking about. This dynamic wait list design which was what was originally put together in this rollout is the same way. There are some variations that could occur based on that but that stepped wedge design works, organization start in a control setting and then randomly get assigned to when they get treatment- that's exactly the same kind of thing. The second issue is about the time period. It is really important to figure out the right period of time that you can balance out the amount of time it takes to implement these interventions and get it an effect, versus ones where communities have to wait a long time. We typically have done that for half a year at a time in suicide prevention programs in schools, but we knew that wasn't going to be really sufficient to get that one.

>> What we have done in our current NIMH trial, like with Peter Wyman, we went to two years of a wait list design and we were able to do that with communities. The third question of how many communities do you need to put into these clusters in each one? We found from a statistical power point of view, it doesn't take many clusters to really enhance the statistical power over the traditional wait list design which only has two cohorts. But if you go to say four cohorts you get a lot more statistical power so the gain you get from going to smaller and smaller number being trained at the same time is not a huge amount from a statistical point of view but it may be very important from a logistics point of view. Most of the time it is going to be dependent upon how many organizations you can train at the same time. That might be the limiting factor. 

>> Do you have any suggestions for determining on which criteria to pair experimental and control groups (e.g., socio-economic status, urban vs. rural setting)? How do you decide which are the most important factors for determining similarity?

>> Well, we've done it in several ways. One of them is from a theoretical point of view. The trials that we did with suicide prevention in schools, we blocked on only two things. This might be a useful kind of thing. There is a small number of pairings in here. We based it on high school versus middle school which turned out to be extremely important developmentally in our outcomes in here and whether the school had a previous history of suicide or not. That actually turn out to be a really good choice in what we did. 

>> In the California schools, we wanted to make these California counties as similar as possible in these clusters. And we selected about eight or so different criteria that we used and measured the population, characteristics of the child welfare system, and things like that in those counties. And we looked at all, basically randomly permuted all of the different possible choices of those counties until we got as close to a balanced design as possible. 

>> So we knew with 40 counties, on maybe on eight dimensions, we could take a look at many different possible combinations of those. We selected about the best out of running a couple thousand potential clusters in those groupings and used that. That is about all I can really say right now. I think it is still really open question. 

>> So in summary, is it correct that having lower level randomization has more power than higher level randomization (as long as the variability between lower levels is low)

>>Yes, the statistical power for lower level randomization is very often much higher, even with a small number of lower level units per higher level. Also see Brown & Liao, 1999.

>> Thanks again. We are at the top of the hour. -- I would like to add my thanks Dr. Hendrix for your presentation and we appreciate your contributions to our program.