Comparative Effectiveness, Safety, and Indications of Insulin Analogues in Premixed Formulations for Adults With Type 2 Diabetes. Event ID: 129966

Transcript of Web Conference


This is the transcript of a Web Conference titled Comparative Effectiveness, Safety, and Indications of Insulin Analogues in Premixed Formulations for Adults With Type 2 Diabetes that took place on February 26, 2009.

Select to access the slide presentation for the Web conference (Powerpoint® slides, 4.58 MB; Text Version).


Scott Smith: Good afternoon, everybody, I am Scott Smith from the Center for Outcomes and Evidence at AHRQ [Agency for Healthcare Research and Quality], where I direct the research program for pharmaceutical outcomes. In the next 5 minutes, I am going to provide you with a very brief overview of AHRQ's Effective Health Care Program to provide some background for this presentation and also to point you to some similar resources that you can use in your practice.

The Effective Health Care Program was authorized in 2003 as part of the Medicare Modernization Act [MMA]. It began approximately 2 years later, when AHRQ actually received an appropriation of $15 million from Congress to support the work. I mentioned the MMA because the Effective Health Care Program has a special focus on health care issues facing the Medicare, Medicaid, and SCHIP [State Children's Health Insurance Program] populations, although our research is much broader.

The program is really a groundbreaking Federal effort to conduct objective, unbiased comparisons of the effectiveness of different health care interventions. We refer to this work as comparative effectiveness research or Comparative Effectiveness Reviews, and this body of work has received a great deal of attention recently with the passage of the American Recovery and Reinvestment Act, which provides expanding resources to do comparative effectiveness research for the Nation. So you will be hearing a lot about comparative effectiveness research in the upcoming months, and I suggest you stay tuned to AHRQ and to other trusted sources of information like APhA [American Pharmacists Association] so you can keep abreast of the information. But for today, the goal of this presentation is to really provide you with information about the program, which is geared toward bringing the best available scientific evidence to bear to make health care decisions.

This slide provides an organizational framework for the Effective Health Care Program. It has three major components, each of which is oriented toward supporting evidence-based practice in health care. The first component of the program is the evidence synthesis part. This involves systematic reviews and summarizing the quality of evidence found in published studies, as well as unpublished studies when they are provided by people like the manufacturers of drugs. For anyone who has done a literature search, you know what a very valuable resource this is, not only as a literature search, but because each study that meets inclusion criteria is critiqued and the body of literature is summarized to explain what is known about the balance of harms and benefits for a particular set of treatment options. And as many of you know who have done literature reviews, the quality of studies varies very widely, and so this is a huge advantage to clinicians, to have a group devoted to finding, evaluating, and summarizing the strength of evidence for a particular set of questions.

Today's presentation is one example of a systematic review. There are many more on AHRQ's Web site that I'll point to you in the future. One important part of reviewing the literature is also uncovering what is not known in a particular field, so all our systematic reviews include a section on identifying research gaps. This is also helpful to a pharmacist because he or she can communicate to patients and physicians where there is uncertainty about a particular therapy or its outcome.

So the second component of AHRQ's Effective Health Care Program is a research infrastructure that provides the ability to conduct new research to fill evidence gaps that have been identified through systematic review.

And then lastly, the third component of our program is called the Eisenberg Center, which is a center devoted to communication and translation of the reports that are produced to make them into to consumer-friendly material, including provider-friendly material and policy-friendly material.

To summarize, the program engages three primary approaches to research on comparative effectiveness. The first approach is to summarize and to synthesize the existing scientific evidence on topics that represent important clinical dilemmas for health care decisionmakers. The second approach is, where there is insufficient evidence on a topic, to generate new evidence to address those knowledge gaps. And the third is to provide meaningful information and translate those sometimes complex technical reports into plain-language guides that highlight the benefits and risks of different options, as well as the level of evidence for different therapies.

This slide shows you, from the perspective of a user, what the outputs of the program are. On the far left, I have shown the research reviews or the systematic reviews that are produced as part of the systematic review process.

The next slide shows the research reports, which are similar to journal articles, that are produced for the new research side of the program. The third products are Technical Briefs. Technical Briefs provide an overview of key issues related to an emerging clinical intervention. Technical Briefs focus on an intervention for which there is limited published data and provide an early description of an emerging area.

Most important for practitioners and pharmacists I think, are our summary guides that are derived from each of the three other products. They are in plain language and are concise ways for busy clinicians to quickly absorb the material that is produced in the research reviews and the new reports and so forth. There are summary guides for patients, there are summary guides for clinicians, and there are summary guides for policymakers.

These products can be used in a variety of ways. I will just point out a couple of them. One is they are often used to inform the development of clinical practice guidelines; they often are not the only source of information but they are one key source when guideline developers are producing guidelines. They can be used for things like coverage decisions and formulary decisions. So they are used as research products in a variety of ways.

The Agency makes a strong push to be transparent, and therefore all of the materials that we produce in the program are available on AHRQ's Web site. This slide lists the direct link to where you can look at the full reports and the summary guides. We also have audiofiles and in addition, we produce the summary guides both in English and in Spanish. So for people who are in areas where you are serving a predominantly Spanish-speaking population or have Spanish-speaking people in your patient population, we have produced the materials to accommodate the Spanish language.

If you are interested in staying in touch, we also offer the ability to push the information out to you. If you go to the Web site, you can sign up for e-mail triggers that allow you to know when new reports are produced. As soon as they are produced an e-mail goes out, you can go right on and get the new report. If there is a consumer guide that is produced, that is also pushed out through e-mail. They are very brief e-mails and, I think. valuable resources to pharmacists.

So with that, I will turn it over to the next speaker.

Barbara Bartman: Hi. Good afternoon, and good morning to those of you who are further west of us. I am going to repeat the welcome because it is my understanding that there have been some technical difficulties with sound. I want to welcome everyone to this Webinar, which is entitled Comparative Effectiveness, Safety, and Indications of Insulin Analogues in Premixed Formulations for Adults With Type 2 Diabetes.

This course is being presented by the Agency for Healthcare Research and Quality's Effective Health Care Program and it is being cosponsored by the American Pharmacists Association.

My name is Barbara Bartman. I am a general internist by training and currently a medical officer at AHRQ and work with the Effective Health Care Program. I am moderating the Webinar.

This Webinar will last 60 minutes, and during this time we will hear from three speakers. You just heard from Dr. Scott Smith, who described AHRQ's Effective Health Care Program. Next you will hear from a speaker who will talk about current research on insulin analogues, and finally we will provide you with some selected suggestions as to how pharmacists can apply their research in practice.

At the end of the program, we will have a Q&A session and answer any questions that you have pertaining to the presentation. You may enter questions to the speakers at any time during the event by entering your questions in the text box in the lower left-hand side of your computer screen.

Today's event is eligible for Continuing Education [CE] credit through the Accreditation Council for Pharmacy Education with the assistance of APhA. To obtain credit, participants must attend the entire program and complete the Continuing Education registration form. We will discuss how to do this at the end of the session.

CE disclosures: As part of providing CE credit, we must provide disclosure information for all of those who participated in putting together this event. To see the disclosure information, go to the Webinar lobby Web page.

And finally, the learning objectives:

  1. To discuss the effectiveness of premixed insulin analogues in achieving optimal glycemic control as compared to traditional insulin regimens;
  2. To compare the difference in premixed insulin analogues with other commonly used insulin preparations, especially in regard to safety and adherence;
  3. To evaluate the effectiveness and safety of the new premixed analogue regimens in individuals on oral antidiabetic agents and individuals with different blood-glucose patterns or types of control; and
  4. To discuss practical and effective therapy options for patients with diabetes.

Okay, since Dr. Smith has presented, we are going to go to the second polling question before I introduce our next presenter. Our second poll question asks, "Are you currently using or planning to use AHRQ's comparative effectiveness products in your setting?

A. Yes, currently B. Yes, in the next 12 months C. Yes, in the next 12 months or later D. No"

I will read it one more time to provide you with an opportunity to answer. "Are you currently using or planning to use AHRQ's comparative effectiveness products in your setting?

A. Yes, currently B. Yes, in the next 12 months C. Yes, in the next 12 months or later D. No"

And again, please submit any questions that you may have in the text box on the lower left hand side of your screen. We will answer these during our Q&A session at the end of the Webinar.

It is now my pleasure to introduce our second speaker, Dr. Rehan Qayyum, who is the Assistant Professor of Medicine at the Johns Hopkins University School of Medicine. He was the primary investigator on this comparative effectiveness research effort, and so if it wasn't for him, it would not have been completed for the Effective Health Care Program.

Dr. Qayyum?

Dr. Rehan Qayyum: Thank you, Dr. Bartman. Hello everyone.

This report, The Comparative Effectiveness, Safety, and Indications of Insulin Analogues in Premixed Formulations for Adults With Type 2 Diabetes, is based on research by the Johns Hopkins Evidence-based Practice Center under contract with the Agency for Healthcare Research and Quality.

According to data from the Centers for Disease Control and Prevention, or CDC, diabetes is the seventh leading cause of death in the United States. Patients with diabetes have a two times higher risk of death than those without diabetes and incur approximately $116 billion annually in direct medical costs. This cost is more than two times higher than patients without diabetes.

Results from large clinical trials of Type 2 diabetic patients have found that intensive control of hyperglycemia decreases mortality by 10 percent and microvascular complications such as diabetic retinopathy by 25 percent. Oral antidiabetic agents are the first line of drug for Type 2 diabetics. Once oral antidiabetic agents fail in achieving optimal control of hyperglycemia in Type 2 diabetics, insulin is commonly added to the treatment regimen. According to data from the CDC, approximately 22 percent of the U.S. Type 2 diabetics were taking insulin in 2007.

The study questions commissioned by the Agency for Healthcare Research and Quality are listed on this and next three slides. This systematic review was designed to address four key questions. First, the systematic review was to look at the effectiveness of premixed insulin analogues in comparison to other treatments for Type 2 diabetes. Second, we wanted to assess the safety, adverse effects, and adherence of premixed insulin analogues. Third, we wanted to assess the effectiveness of premixed insulin analogues in different subpopulations. And lastly, we wanted to examine their effectiveness and safety in combination with oral antidiabetic agents and in individuals with different blood glucose patterns or individuals requiring different types of blood glucose control.

Before I move on to the next slide, let me say a few words about premixed insulin analogues. These are human insulin molecules with minor structural changes. These structural changes have no impact on glucose-lowering ability of insulin, but impart important pharmacokinetic properties that allow better control of the onset and duration of insulin activity.

Premixed preparation of insulin analogues consists of mixture of rapid-acting and intermediate-acting formulations of these analogues. These premixed insulin analogues have a faster onset of action, with peak activity in about 2 1/2 hours, in a comparison to premixed human insulin preparations, which achieve peak activity in about 4 hours. There is also a faster decline in insulin activity once a peak is reached with premixed analogues.

To identify studies that addressed key questions of our study, we performed an extensive literature search. We searched electronic databases, MEDLINE, EMBASE, the Cochran Central Register of Controlled Files (or Central), and Cumulative Index to Nursing and Allied Health Literature from inception to February 2008. We also reviewed reference lists of included articles, recent issues of 30 field-specific medical journals, the Food and Drug Administration [FDA] and European Medicine's agency Web sites for the premixed insulin analogues, unpublished data from premixed analogue manufacturers, and Web sites for public registries of clinical trials, such as clinicaltrials.gov and clinicalstudyresults.org. Our aim was not to miss any public study that has addressed this topic.

We included studies that compared a premixed insulin analogue approved by FDA as of February 2008 to any other drug for adults with Type 2 diabetes and evaluated the outcomes of our interest. The outcomes included fasting glucose, postprandial glucose, and hemoglobin A1c, and we called these outcomes "Intermediate Clinical Outcomes." We also included hard critical outcomes such as all-cause mortality, cardiovascular morbidity and mortality, and microvascular outcomes such as diabetic retinopathy. We collected data on adverse events such as hypoglycemia and weight gain. Data on quality of life were abstracted if reported. We included randomized controlled trials, controlled clinical trials, and observational studies with control groups regardless of the duration of followup or sample size. We did not include results for hemoglobin A1c in our trial if the duration of followup was less than 12 weeks in that trial, for obvious reasons. We also did not include the results of progressive outcomes from crossover trials.

Two investigators reviewed the titles, abstracts, and full articles independently for inclusion and abstracted data by using standardized forms. For intermediate outcomes and adverse effects, we pooled the results of individual studies using a random effects model. For clinical outcomes, we included all studies that reported any information about clinical events such as all-cause mortality, and cardiovascular mortality and morbidity.

All analysis followed the Intention to Treat principle. While many studies did not report on hard clinical outcomes, few studies that reported these outcomes had very few events. The presence of real events in pooling data makes any single method unreliable. We therefore used several different statistical approaches to confirm the robustness of our results.

We classified evidence pertaining to key questions into three basic categories: "high-grade" evidence indicating confidence that further research is very unlikely to change our confidence in estimated effects; "moderate-grade" evidence indicating that further research may have an important impact on our confidence in the estimates of effects; and "low-grade" evidence indicating that further research is very likely to have an important impact on the confidence in the estimates of effects and is likely to change the estimates from our study. We graded the evidence as "no evidence" if there were no studies evaluating the drug comparison.

And here I will be presenting results. Our literature search found 45 studies that reported on at least one of the intermediate clinical outcomes on all adverse events. All were randomized controlled trials except two. In two of these studies, patients were enrolled consecutively. In one of these two studies, patients were enrolled consecutively and followed prospectively, while in the other study, data were obtained from the medical records database of a large employer.

Among the randomized controlled trials, 23 were parallel-armed and 20 were crossover trials. The median duration of followup in these trials was 16 weeks, with a range of 1 day to 2 years. Median age of patients in these studies was 59 years, and approximately 52 percent of the subjects were males.

This slide shows a forest plot, and it compares the fasting glucose-lowering effect of premixed analogues with other agents. The left-hand side of the figure lists the name of competitors and the premixed analogue to which it is compared. The middle part of the figure gives the weighted mean difference of fasting blood glucose of each comparison with 95-percent confidence in results in a graphic form, and numerical values are on the right-hand side of the figure. The upper third of the figure shows that long-acting insulin analogues are clearly better than premixed insulin analogues in lowering fasting glucose. The difference was about 12 milligrams per deciliter between long-acting analogues and premixed analogues combined, and ranged from 6.4 milligrams per deciliter for Insulin Aspart 70/30 to 24.7 milligrams per deciliter for Insulin Lispro 50/50.

The middle part of the figure compares premixed human insulin preparation with premixed analogues. Overall, premixed human preparations seem to be better than premixed analogues, although 95-percent confidence intervals crossed midline. In contrast, the lower third of the figure shows that premixed insulin analogues were significantly better than noninsulin antidiabetic agents in lowering fasting glucose.

This forest plot displays results for postprandial glucose. Most studies reported glucose levels 2 hours after meals, but some studies reported results 90 minutes after meals. For this analysis we pooled data from these two types of studies. As compared to fasting glucose, which was shown in the previous figure, premixed insulin analogues were clearly superior to long-acting insulin analogues, premixed human insulin, and noninsulin antidiabetic agents in lowering postprandial glucose. This is consistent with what one would expect based on the faster onset effect of these premixed analogues.

Hemoglobin A1c is the most commonly used clinical measure to follow glucose control in diabetic patients. It assesses average glucose levels that body is exposed to over the 12-week period prior to the test. Premixed insulin analogues were similar to premixed human insulin in lowering A1c. In contrast, premixed analogues were superior to long-acting insulin analogues and noninsulin antidiabetic agents in lowering A1c, and the lowering effect was an additional one-half percentage point.

However, these results can be due to the underlying study designs. In several studies, the total daily dose of long-acting insulin analogues was less than the premixed insulin analogues dose, and this difference may have resulted in the observed benefit of premixed analogues. Similarly, in several studies the dose of noninsulin antidiabetic agents was fixed throughout the study, while the dose of premixed analogues was allowed to be adjusted to optimize glucose control. This difference may have resulted in the findings on this slide.

Hypoglycemia is an important adverse outcome, and Type 2 diabetic patients on insulin are at risk of this adverse event. The left side of this forest plot is different from the previous plot. Instead of listing individual premixed analogues, it lists different grades of hypoglycemia. Overall, long-acting insulin analogues and noninsulin antidiabetic agents appear to be better than premixed insulin analogues in reducing the risk of hypoglycemia. Premixed insulin analogues appear to have risks of hypoglycemia which are similar to premixed human insulin preparations.

This slide shows the results for weight gain. There were little data on the effect of premixed analogues on weight change as compared to other agents. Patients using long-acting insulin analogues and noninsulin antidiabetic agents had smaller weight gain as compared to patients using premixed analogues. However, this difference could be due to the lower dose of long-acting insulin analogues as compared to premixed analogues dose and due to the use of [inaudible] in several studies of noninsulin antidiabetic agents. There were insufficient data on the comparison of premixed analogues with premixed human insulin. Only two studies comparing Insulin Aspart 70/30 with premixed human insulin reported weight change. The results were not statistically significant in one study and the second study did not report statistical significance or provide sufficient data.

There were very little data on other comparisons. We found only two studies that compared a premixed analogue with a rapid-acting insulin analogue; two studies that compared a premixed analogue with a combination regimen of long-acting and rapid-acting insulin analogue, also known as basal-bolus regimen; two studies that compared a premixed insulin analogue to intermediate-acting insulin; and one study that compared a premixed analogue with a combination of rapid-acting analogue with intermediate-acting human insulin. Due to sparseness of the data, we were unable to draw firm conclusions about these comparisons.

Moving on to clinical outcomes—there were very few data for individual comparisons, and as before, we combined all premixed analogues into one group and comparators into the other group. Although we did not find statistically significant differences between premixed analogues and the competitors in terms of all-cause mortality, cardiovascular mortality, or cardiovascular morbidity, looking at this forest plot, a suggestion of harm can be seen in the pooled-up chances for all outcomes except cardiovascular morbidity. However, these point estimates were based on few absolute events in only a few studies in which clinical outcomes were not the primary end point. Data from future studies may change our conclusions. For microvascular outcomes, we found insufficient or no evidence.

As compared with premixed human insulin that needs to be given about 30 minutes before meals, premixed insulin analogues can be given with meals. This flexibility may improve the overall quality of life. We found only six studies that evaluated quality of life. Of these six, only four studies used a validated quality-of-life scale. In one of these four studies, there were some differences between the premixed insulin analogue and its competitor. This study assessed six quality-of-life measures; only one—psychological distress—showed a statistically significant difference favoring premixed insulin analogues over oral antidiabetic agents. Thus we cannot draw firm conclusions regarding quality-of-life outcomes for any comparison.

We also collected data from the studies that compare patients taking combinations of premixed insulin analogues and oral antidiabetic agents with patients taking only premixed insulin analogues. In the small number of studies evaluating this comparison, there was no difference between the two treatments in fasting and postprandial glucose, incidence of hypoglycemia, weight change, or clinical outcomes. However, we found that combination of premixed analogues and oral antidiabetic agents was better in lowering A1c than premixed analogues alone.

We did not find any evidence on adherence to treatment regimen or effectiveness and safety of premixed analogues in subpopulations of interest as outlined in our key questions; in individuals with different intensity of glucose control; and in targeting fasting versus postprandial glucose control.

This slide summarizes most outcomes by comparison. Upward arrows mean that insulin at the top of the column is better than premixed analogues. Downward arrows mean otherwise. Horizontal arrows mean that both are similar. An "X" in the field means that there are no data on that comparison.

In summary, when compared to long-acting insulin analogues, we found that premixed analogues are better in lowering A1c and postprandial glucose, but less effective in lowering fasting glucose. Premixed analogues are similar to premixed human insulin in lowering fasting glucose and A1c, but better in lowering postprandial glucose. Risk of hypoglycemia with premixed analogues is similar to premixed human insulin, but hypoglycemia risk is higher when compared to long-acting insulin analogues.

The major gap in evidence that we noticed was that our search did not find any study that was specifically designed to evaluate hard clinical outcomes. The few studies that reported clinical outcomes were of relatively short duration and were neither designed nor powered to assess clinical outcomes. We also did not find sufficient data on quality of life or adherence to treatment regimen.

In conclusion, based on the findings of this systematic review, we recommend that therapy should be individualized. In the presence of elevated hemoglobin A1c, premixed insulin analogues seem better than long-acting insulin analogues and oral antidiabetic drugs. There does not appear to be any difference between premixed analogues and premixed human insulin in preparations.

In patients with fasting hyperglycemia, long-acting insulin analogues seem to be a better choice than premixed analogues. In patients with postprandial hypoglycemia, premixed insulin analogues seem preferable to long-acting analogues, premixed human insulin, or oral antidiabetic agents. If risk of hypoglycemia is a major concern, then long-acting insulin analogues seem to have much lower risk of hypoglycemia than premixed insulin analogues. There does not appear to be any difference between premixed analogues and premixed human insulin.

This is the list of investigators who contributed to this study in a significant manner. Thank you, and I will go back to Dr. Bartman.

Barbara Bartman: Thank you very much, Dr. Qayyum. Greatly appreciate it, that was a great study that you did.

As I mentioned previously, Dr. Carmen Kelly, who is a pharmacist at the Agency ,was going to provide you with some information on the utility and value of the systematic review. However, she is sick today, so I basically am going to take some of her notes and her information and discuss with you some practical applications of the systematic review.

I think, as you can discern from the systematic review, there still are a lot of questions that need to be answered. What I would like to do is discuss a few in the next several minutes, some of the "real world" applications or the value and utility of the research that has just been presented.

As you likely gleaned from the discussion, to really implement practice changes the results of this research require further confirmation. We need more studies; in some cases, studies that haven't even been done yet. However, it is possible to still consider the utility and value of the systematic review for an individual pharmacist, for further pharmaco-epidemiologic research, and also for education.

First, I would like to discuss the implications for practice. There are many findings—I could go on and on about the number of implications for practice—however, we have been selective in choosing which ones we would talk about, or perhaps recommend. Given that there are now a multitude of insulin preparations available on the market and the potential need for frequent changes in patients and their dosages, pharmacists must be able to ensure that patients adhere to their insulin regimen, their diet, that they are consistent in their activities. These are all necessary to maintain an acceptable glucose level and to avoid hypoglycemia and weight gain. Based on the results of the systematic review, it would seem reasonable for a pharmacist or provider to continue a patient on a regimen of premixed human insulin that they have been on or a basal analogue regimen if they have been responding appropriately (i.e., their hemoglobin A1c levels are within an acceptable range and they are not experiencing any side effects).

The change to premixed insulin analogues would seem like an acceptable alternative if individuals are having difficulty controlling their postprandial blood sugar levels but not fasting sugar levels (i.e., their hemoglobin A1c levels are high despite acceptable or unacceptable fasting levels and high postprandial levels).

It is necessary and important to ensure that patients make informed choices about their treatment, because only they know about what they can tolerate, what they can afford. If cost is an issue, then patients may elect to cover themselves with regular human insulin after meals. It may be the only realistic treatment or option for them. And of course, in regard to safety, one must always be cognizant of the risk of hypoglycemia and monitoring of blood sugar levels as well as weight gain.

In terms of implications for research, the studies used in this systematic review were largely studies with efficacy (i.e., the studies were done under ideal conditions). Ultimately, to truly understand the benefit of the premixed insulin analogues in the population, comparative effectiveness research will be necessary to further our knowledge about which therapies work best for which individuals—i.e., do certain subgroups benefit more than others: the old, the young, individuals of different gender, race, ethnicity, disease severity, and those with comorbid conditions?

Many questions cannot be answered in this systematic review because there were not enough efficacy studies to be examined in a systematic way. These in particular include examining basal-bolus therapy, a regimen where a long-acting insulin analogue is used with a rapid-acting analogue against the standard treatment.

In addition, studies need to be of longer duration to really understand the sustained effect of treatment with these newer agents compared with human insulin, especially in long-term clinical outcomes such as coronary disease, nephropathy, and retinopathy, and not just laboratory values such as fasting sugars, postprandial glucose levels, and hemoglobin A1c's.

Knowledge about the research that has been done on these new insulins is necessary to be able to answer patients' questions about them. Pharmacists, even more importantly, need to be able to discuss with the physician when it is best to start a patient on premixed insulin analogues.

As the review shows, there is no significant difference between human insulin and premixed analogues on fasting blood sugar levels. Based on this finding, a patient doing well on human premixed insulin may not necessarily benefit from a change to a premixed preparation. However an individual who is experiencing poor control on a regimen with basal analogues or human insulin and has high hemoglobin A1c's may benefit from a change. Such information is useful in a physician consultation if a drug change is considered. Ultimately, we want to be able to educate patients about their insulin regimens and also discuss with health care providers the best therapy for their patients.

Okay, we are now going to take online questions related to our speakers' presentations. If you would like to ask a question, please type it in the text box on the lower left-hand side of your computer screens.

Where can I get a copy of the report? That's a very important question, which we will get into a little bit later. These slides will be posted online within 2 business days on the registration Web site and soon after on our EHC Web site, so stay tuned.

Rehan, is there evidence of titration of different insulin preparations?

Rehan Qayyum: Studies that we looked at did not study titration to different insulin preparations. If I understand the question correctly, what is being asked is about switching from one insulin preparation to another insulin preparation? And so none of the studies we looked at was actually looking at this particular question. When we were doing our search, we did find a few observational studies that were done in this way, but first they did not fulfill our inclusion criteria, and second the study quality in each of those observational studies was really low and so it is very difficult to have any conclusion drawn from any of those studies.

Barbara Bartman: Thank you. It looks like we are running low on time, so I am going to ask Scott one more question. Are there any materials that I may provide my patients such as a consumer guide? If so, where are the materials available?

Scott Smith: Thank you, Barbara. So all of the materials are available on AHRQ's Effective Health Care Web site. That is effectivehealthcare.ahrq.gov. There are consumer guides related to this report as well as other reports that are downloadable in pdf format. You are also able to order them in printed format from AHRQ's Clearinghouse, and that information is available on the slide presentation.

The full report written by the Johns Hopkins Evidence-based Practice Center is available today on AHRQ's Web site; you can download that if you are also interested in seeing the full report. It was also copublished in the Annals of Internal Medicine, and so you can see it from Annals as well.

Barbara Bartman: Great. If you have any other question after the Webinar, please email us at AHRQScience2Practice@ahrq.hhs.gov. This will be on the slide presentation as well.

A few logistics as well before we wrap up: In terms of obtaining CE credit, please visit www.pharmacists.com by March 13, 2009, and enter the verification code provided on the slide before you: DCI226. You will receive a feedback form at this Webinar to provide us with your input. We really ask and please need your time to complete this form; it would be very helpful for us.

Again, thank you for joining us today. We hope despite the technical difficulties—and I am sure many of you can sympathize with our experience—we all hope that you join us again on May 1st for our second Webinar, which will be entitled Atypical Antipsychotic Drugs and the Risk of Sudden Cardiac Death. This is based on an article just published in the New England Journal of Medicine. We will send everyone an e-mail with the Web site and instructions for this Webinar.

Thank you, and that concludes our Webinar today. If you would like to submit any questions, again please e-mail us at AHRQScience2Practice@ahrq.hhs.gov. You can also use this e-mail address to nominate topics for future Effective Health Care reports if there is something of interest to you in the field of diabetes or any other topic.

And as I mentioned previously, the presentation slides will be posted online on the registration Web site within 2 business days, and soon after on our Effective Health Care Web site. This concludes today's Webinar. Thank you all speakers and everybody who helped put this together.

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