Measuring Health-Related Quality of Life for Patients With Diabetic Re

Disposition of Comments

Project ID: DBTR0610. Comments received from draft review on diabetic retinopathy.

The Agency for Healthcare Research and Quality's (AHRQ) Technology Assessment (TA) Program supports and is committed to the transparency of its review process. Therefore, invited peer review comments and public review comments are publicly posted on the TA Program Web site at http://www.ahrq.gov/clinic/techix.htm within 3 months after the associated final report is posted.

This document presents the peer review comments and public review comments sent in response to the draft report, Measuring Health-Related Quality of Life for Patients With Diabetic Retinopathy, which was made available for comment on the AHRQ Web site. The final version of the report is available online.

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Contents

Select for Table 1: Peer Review Comments.

Select for Table 2: Public Review Comments.

 

Table 1: Peer Reviewer Comments

ReviewerSectionReviewer CommentsAuthor Response
1GeneralOverall, this is a well designed, clearly written assessment. The purpose of the assessment is clearly stated, methods are sufficiently delineated, and the scope of the projected precisely defined. The discussion and conclusions are supported by the aim and methods of the assessment. The use of intravitreal injections of steroids and anti-VEGF agents or treatment of diabetic retinopathy and diabetic macular edema should be included in appropriate interventions.We have added a sentence to the ES & introduction: "Serial intravitreal injections of triamcinolone have been introduced as a treatment option as they have been shown to be effective at reducing diabetic macular edema; however, their use is become less common due to significant adverse effects including elevated intraocular pressure and cataract formation. Ranibizumab and becvacizumab are being used with increasing frequency for the treatment of macular edema; however they have not yet been approved for use in this condition by the Food and Drug Administration."
  I do believe that my comments concerning impact on visual acuity and visual function of interventions (intravitreal injections, laser photocoagulation, vitrectomy surgery, low vision rehabilitation) vs. no interventions should be included in the discussion as a consideration in the interpretation of satisfaction regarding treatments. Clearly, an intervention may result in some vision deterioration, but this status cannot be compared with a vision level that may have occurred if no intervention had been initiated.We have added a note in the introduction section, which reads: It is important to note that treatment of DR is not always aimed at restoration of pre-disease visual acuity, but rather at limiting further deterioration. Patients may report a decrease in visual acuity immediately after therapy, which may manifest in low initial perceptions of treatment satisfaction. However, results from the Early Treatment Diabetic Retinopathy Study demonstrate that early treatment with either panretinal photocoagulation or vitrectomy prevents long-term disability due to blindness.
 Executive SummaryThe Executive Summary is well organized and clear in its presentation. There is appropriate use of Tables and the Tables contribute to the clarity of presentation. Interventions vs no interventions cannot be evaluated.Thank you for your comment.
 Page ES-1, 1st and 2nd paragraphsReferences 4 and 5 are cited out of order.We added additional text to these two paragraphs to match the introduction of the main report, thereby correcting the order of the citations. Since there is no reference list for the executive summary we wished to keep the reference numbers identical to those of the main report.
 Page ES-1, 2nd paragraphSuggest revision to reflect more comprehensive approach to management of diabetic retinopathy and diabetic macular edema: (1) Periodic (generally annual or more frequent if necessary) retinal assessment for presence and degree of diabetic eye disease, (2) optimized glycemic control to reduce the risk of onset and progression of diabetic retinopathy (not to prevent the progression as stated in the present text), (3) control of known risk factors and associated risk factors for progression of retinopathy (e.g., blood pressure, dyslipidemia, elevated cholesterol, renal disease, abdominal obesity), (4) direct ocular therapy when indicated, and (5) vision rehabilitation/low vision aids to maximize vision if there is a loss of vision.We have amended the text (ES & Introduction) to read as follows: "The mainstay of DR treatment is aimed at reducing the risk of onset and limiting the progression of the disease. Therefore, retinal assessments should be performed on a regular basis to determine the presence and degree of DR, glycemic control should be optimized, and known risk factors such as blood pressure, dyslipidemia, elevated cholesterol, renal disease and abdominal obesity should be controlled. Direct ocular therapy should be prescribed when indicated, while vision rehabilitation and low vision aids should to be used to maximize vision if there is a loss."
 Page ES-1, 2nd paragraphTreatment for diabetic macular edema should also include reference to intravitreal injection (cf. The Diabetic Retinopathy Clinical Research Network Writing Committee: Michael J. Elman, MD; Lloyd Paul Aiello, MD, PhD; Roy W. Beck, MD, PhD; Neil M. Bressler, MD; Susan B. Bressler, MD; Allison R. Edwards, MS; Frederick L. Ferris III, MD; Scott M. Friedman, MD; Adam R. Glassman, MS; Kellee M. Miller, MPH; Ingrid U. Scott, MD, MPH; Cynthia R. Stockdale, MSPH; Jennifer K. Sun, MD, MPH. Randomized Trial Evaluating Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema. Ophthalmology 2010;117:1064�1077.)We have added a discussion regarding intravitreal injection as noted above. We have included this reference to the report as well.
 Introduction/Background: Page 1, 3rd paragraph, 3rd lineReplace "American Association of Ophthalmologists" with "American Academy of Ophthalmology." It would also be reasonable to include recommendation of other professional societies such as the American Optometric Association and the American Diabetes Association (ADA).The 'American Association of Ophthalmologists' has been replaced with 'American Academy of Ophthalmologists' in the body of main report as well as the executive summary. We have added the AOA and ADA to the ES and introduction.
 Page 1, 3rd paragraph, last sentenceThe quoted report applied to the VA and was received with quite a bit of controversy. If this sentence is retained it might be reasonable to include the ADA's statements regarding annual eye examination and the role of remote retinal imaging/telemedicine.We have added the ADA to the list of organizations recommending annual eye examinations for people with diabetes (see above).
 Page 1, 4th paragraphAs in Executive Summary, suggest revision to reflect more comprehensive approach to management of diabetic retinopathy and diabetic macular edema: (1) Periodic (generally annual or more frequent if necessary) retinal assessment for presence and degree of diabetic eye disease, (2) optimized glycemic control to reduce the risk of onset and progression of diabetic retinopathy (not to prevent the progression as stated in the present text), (3) control of know risk factors and associated risk factors for progression of retinopathy (e.g., blood pressure, dyslipidemia, elevated cholesterol, renal disease, abdominal obesity), (4) direct ocular therapy when indicated, and (5) vision rehabilitation/low vision aids to maximize vision if there is a loss of vision.We have amended the text to read as follows: The mainstay of DR treatment is aimed at reducing the risk of onset and limiting the progression of the disease. Therefore, retinal assessments should be performed on a regular basis to determine the presence and degree of DR; glycemic control should be optimized, and known risk factors such as blood pressure, dyslipidemia, elevated cholesterol, renal disease and abdominal obesity should be controlled. Direct ocular therapy should be prescribed when indicated, while vision rehabilitation and low vision aids should to be used to maximize vision if there is a loss.
 Page 1, 4th ParagraphAs in Executive Summary, treatment for diabetic macular edema should also include reference to intravitreal injection (cf. The Diabetic Retinopathy Clinical Research Network Writing Committee: Michael J. Elman, MD; Lloyd Paul Aiello, MD, PhD; Roy W. Beck, MD, PhD; Neil M. Bressler, MD; Susan B. Bressler, MD; Allison R. Edwards, MS; Frederick L. Ferris III, MD; Scott M. Friedman, MD; Adam R. Glassman, MS; Kellee M. Miller, MPH; Ingrid U. Scott, MD, MPH; Cynthia R. Stockdale, MSPH; Jennifer K. Sun, MD, MPH. Randomized Trial Evaluating Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema. Ophthalmology 2010;117:1064�1077.)We have added a discussion regarding intravetrial injection as noted in the response to the general comments. We have included this reference to the report as well.
 Page 1, 5th paragraph et passimAdvise avoiding the use of the word "prevention" when referring to onset and/or progression of diabetic retinopathy and diabetic macular edema and vision loss/blindness since the present treatments reduce the risk of onset and progression of disease and reduce the risk of vision loss.The text has been changed to read: Vision loss is particularly debilitating for patients with diabetes because treatment success to limit progression of their diabetes depends upon their ability to read a glucometer and inject subcutaneous insulin.
 Page 2, 3rd paragraph, last sentenceConsider adding listing additional elements that affect QOL for a person with diabetes; e.g., complications and co-morbidities (e.g., renal disease/dialysis, neuropathy, gastroparesis, amputation, impotence/ED, etc.)We have amended to the text to read as follows: In the case of patients with diabetes, comorbidities and complications such as renal disease or dialysis, neuropathy, gastroparesis, amputation, impotence and erectile dysfunction all play a part in influencing QOL. Furthermore, the level of visual acuity, glycemic control, and duration of disease can impact directly on vision-related QOL.
 MethodsMethods are clearly expressed, scientifically sound, and appropriate for the stated goals of the paper.Thank you for your comment.
 ResultsResults are clearly presented.Thank you for your comment.
 Discussion Page 29, 1st paragraphThe review actually does not assess the effectiveness of interventions for DR to HRQL, but rather assess the vision of patients with diabetes and DM on HRQL. The underlying difficulty is that the questionnaires do not ( and cannot) compare the visual acuity and visual function of a person who has had laser photocoagulation, vitrectomy, or intravitreal injection to what the visual acuity or visual function might have been without such interventions in the same individual. For example, a person may have 20/20 visual acuity but still have clinically significant macular edema. This person may have focal laser photocoagulation or an intravitreal injection that results in a slight reduction of visual acuity (e.g., 20/25), and this person may report that vision is worse following treatment. However, multicenter clinical trials consistently show that the risk of moderate vision loss (doubling of the visual angle) from clinically significant macular edema is reduced by 50% or more with laser photocoagulate, suggesting that the person's vision following laser photocoagulation would need to be compared to the potential visual acuity reduction of 20/40; such a comparison is not possible, suggesting a weakness in any questionnaire on visual acuity or visual function for a person receiving laser photocoagulation. Similarly, a person may have high risk proliferative diabetic retinopathy and still have 20/20 vision or better, which may be slightly reduced following scatter (panretinal) laser photocoagulation. This person may report that vision is worse after laser treatment, but studies once again demonstrate that the risk of legal blindness and sever vision loss from proliferative diabetic retinopathy is dramatically reduced. Without laser treatment or vitrectomy, about 50% of patients with proliferative diabetic retinopathy become legally blind within 5 years, compared with less than 5% treated with laser and /or vitrectomy in the Early Treatment Diabetic Retinopathy Study. (Ferris FL III. How effective are treatments for diabetic retinopathy? JAMA 1993;269:1290-1291.)The text has been amended to read: "Using a comprehensive search strategy and concerted efforts to avoid publication and selection bias, this review identified the evidence on the effect that interventions for DR have on HRQL."
 Page 30, 2nd paragraphPlease see comment 1 directly aboveThe text has been changed to read: Only one generic HRQL measure has been used to assess the impact that interventions for DR have on HRQL in patients with DR.
 Page 3, Subheading "Impact of interventions on HRQL."This summary is excellent.Thank you for your comment.
 TablesAll included tables are clear and support discussion in the text of the document.Thank you for your comment.
 FiguresFigure 1. Useful figure
Figure 2. Useful figure
Thank you for your comment.
 AppendicesAppendix A. Search strategies. Search strategies appear appropriate and complete
Appendix B. Inclusion/Exclusion Form. Form is appropriate.
Appendix C. Excluded studies. Unable to comment
Appendix D. Excellent summary table.
Appendix E. Samples HRQL assessment tools. Useful
Appendix F. Useful
Thank you for your comments on the appendices.
 ReferencesAppropriate for the document.Thank you for your comment.
2GeneralThis report reviews the most relevant studies in existence that report on health-related quality outcomes in diabetic retinopathy. The search strategy appears sounds and the authors methodology resulted in a review and summary of the available data. The end conclusion is that there are not many studies out there that report of health quality outcomes in diabetic retinopathy and those that do are of insufficient quality to make any recommendations for treatment. The authors conclude that further studies and RCTs are warranted.Thank you for your comments.
 Executive SummaryThe summary reads well and highlights the methodology, results, and conclusions without getting into too much detail that would bog down the reader.Thank you for your comment.
  Suggestion: include the names of the 6 databases searched in the methods section.We added the names of the databases to read as follows: We conducted systematic and comprehensive searches in was run in the following databases: MEDLINE®, EMBASE®, PsychINFO®, Cochrane Central Register of Controlled Trials®, CINAHL Plus full text, and Scopus to identify relevant studies to address the Key Questions.
 Introduction/BackgroundThis section is complete with relevant citations and framework for the remainder of the report.Thank you for your comment.
 MethodsThe search methods described and the review method for the papers identified appear valid and minimize bias. Statistics: a description of means and 95% confidence intervals was an excellent choice for comparison.Thank you for your comment.
 ResultsClearly reported.Thank you for your comment.
 Discussion/ConclusionNone of the studies reported on in this manuscript had sufficient evidence to make any treatment recommendations for diabetic retinopathy. The authors recommend more studies, specifically RCTs, that include patients from the United States.No action required.
  Why was a period of 6 months chosen for stabilization of vision? Could 3 months suffice, as that is a commonly used clinical endpoint for many retinal surgical interventions. If you wanted a longer time period, why not chose 12 months then?Three months is not long enough to evaluate these treatments. A priori, we anticipated that few studies would report 12 month data, and felt that 6 months was a reasonable compromise.
  The authors report the studies in this manuscript have insufficient evidence for making recommendations based on the fact that there was a high risk of bias in the studies, though it is not explicitly stated what those biases were. Please clarify.We have clarified the bases for the high risk of bias by explicitly referring to before-after and cohort studies: ES-4 and methods section: "The following four domains were examined: risk of bias (including study design and study conduct), consistency, directness, and precision."
P ES-8 p 31: "However, overall this collection of studies is at high risk of bias due to weak study designs (before-after and cohort studies) and poor implementation."
P 22 summarizes the methodological quality of the included studies.
 TablesThe tables are well organized and clear.Thank you for your comment.
 FiguresAppropriateThank you for your comment.
 AppendicesInclusion of the search terms for studies, as well as sample questionnaires is appropriate.Thank you for your comment.
 ReferencesThe references in this report appear to be extensive and complete.Thank you for your comment.
3GeneralIn general, this is a comprehensive review of existing instruments and results for measuruing health-related quality of life for patients with diabetic retinopathy (DR). My major criticism is that the authors do not mention the importance of measuring HRQL in utilities (scalable units between 0 and 1) that can be used in cost-effectiveness analysis (CEA). While it is important to measure patient preferences, it is also extremely important to be able to incorporate those preferences into CEA models in order to compare therapies within and across disease states. It seems that none of the current DR instruments readily translate into utilities. This oversight should be noted, and I think the recommendations should include that HRQL for DR should also be measured in a way that incorporates overall health utility in addition to vision-specific utility.While we agree that it would be useful to identify utility-based measures, this was beyond the scope of the current TA.
 Executive SummaryGood overall.Thank you for your comment.
 Page ES-11The reference to the PKC DRS 2 trial is too oblique and should be further explained or excluded.We have removed the last sentence from this paragraph in the ES and the discussion section.
 Page ES-14 and other Recommendations sectionsBullet 5 stating that RCTs should be conducted to minimize the risk of bias, and referring readers to the CONSORT statement is certainly true, and obvious, but has no place in this report given its lack of specific relation to HRQL in DR.We believe this recommendation serves as a reminder to researchers about good research and reporting practice.
 Introduction/BackgroundThe first sentence of the introduction in the Executive Summary and in the main document states: that the "estimated crude prevalence among Americans over the age of 40 was 28.5%": the authors almost certainly mean among Americans with diabetes.Thank you. This has been corrected in the ES and introduction, and reads as follows: In 2005�2008, the estimated crude prevalence among Americans with diabetes over the age of 40 was 28.5 percent.
 MethodsAdequate and appropriately described.Thank you for your comment.
 ResultsComprehensive and clearly presentedThank you for your comment.
 Discussion/ConclusionThe lack of discussion of the use of measurement of HRQL for utilities in CEA is a major oversight.While we agree that it would be useful to identify utility-based measures, this was beyond the scope of the current TA.
 Pages 30-31Bullet 6 should be a subset of bullet 2, and bullet 5 should be deleted, as indicated above.We have moved bullet 6 to bullet 3. We disagree that bullet 5 be deleted; it is now bullet 6.
 TablesClear.No action required.
 FiguresClearNo action required.
 AppendicesNoneNo action required.
 ReferencesInclude references to measuring utilities for CEANo change. We did not identify utility-based measures.
4GeneralThis study basically states there is no quality evidence to support an association between the current interventions for diabetic retinopathy and an improvement in quality of life. The problem, of course, is the tool(s) that is(are) being used rather than the appropriateness of the intervention. The authors appear to be supportive of the diabetic retinopathy-specific tools that were developed in the UK in 2005. These diabetic retinopathy specific HQRL tools are likely more useful but a major problem with diabetic retinopathy-related HQRL measurements is that the treatment of diabetic retinopathy ideally and typically occurs prior to any vision loss or with the intent to prevent further vision loss. Therefore vision-related HQRL measurements are less practical for treatments for diabetic retinopathy which universally have a main goal of stabilizing vision rather than improving vision. Of course, HRQL related to the discomfort/inconvenience, etc of the treatment itself does need to be considered. There are no major problems with this paper except that it does not provide any significant new information to work with other than trying to justify future studies with RetDQoL and RetTSQ.No changes have been requested.
 Executive SummaryNoneNo action required.
 Introduction/Background:Would be helpful to discuss treatment of diabetic retinopathy more specifically especially with regards to the main goal of treatment to prevent or reduce vision loss for most interventions. Need to include some mention of intravitreal anti-VEGF therapy.We have added the following (p. 1): "Therefore, retinal assessments should be performed on a regular basis to determine the presence and degree of DR; glycemic control should be optimized, and known risk factors such as blood pressure, dyslipidemia, elevated cholesterol, renal disease and abdominal obesity should be controlled. Direct ocular therapy should be prescribed when indicated, while vision rehabilitation and low vision aids should to be used to maximize vision if there is a loss."
We have added information about intravitreal anti-VEGF therapy in the ES and introduction (p.1).
 MethodsAppropriateThank you for your comment.
 Discussion/ConclusionAppropriateThank you for your comment.
  Conclusions are reasonable. Unfortunately, this study does not add much information to the current literature other than to state there is a paucity of quality HRQL studies on diabetic retinopathy treatment. In fact, a major current intervention, intravitreal anti-VEGF therapy for diabetic macular edema, has not been studied at all. Again the authors should stress that intervention for diabetic retinopathy does not always have a goal of vision improvement � i.e. goal is usually to prevent vision loss. Obviously vision loss is considered a major HRQL issue but lack of improvement in vision or vision-related HQRL measurement does not imply that treatment for diabetic retinopathy is not effective.0The reviewer is correct in noting that, to date, no studies have assessed the impact of anti-VEGF therapy on HRQL. We have added the following to the ES and introduction: It is important to note that treatment of DR is not always aimed at restoration of pre-disease visual acuity, but rather at limiting further deterioration. Patients may report a decrease in visual acuity immediately after therapy, which may manifest in low initial perceptions of treatment satisfaction. However, results from the Early Treatment Diabetic Retinopathy Study demonstrate that early treatment with either panretinal photocoagulation or vitrectomy prevents long-term disability due to blindness.
 TablesNoneNo action required.
 FiguresNoneNo action required.
 AppendicesAppendices: Too long. Do not need to list all excluded studies. Would include reference for the HRQL tests but not print out the entire questionnaires.The list of excluded studies is required as a part of a TA for AHRQ.
AHRQ requested that the HRQL questionnaires included in the appendix.
 ReferencesAdequateNo action required.

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Table 2: Public Review Comments

ReviewerAffiliationReviewer Comments
1    Lars BirgersonGenentech, Inc.EPC Response: Thank you for your letter*; we appreciate the careful consideration you have given our report. We have reviewed the additional trials that you identified in Clinicaltrials.gov, as well as updated our search in the registry to April 2011. As a result we have included eight new trials in the appendix A table outlining the current state of unpublished trials investigating interventions for diabetic retinopathy or diabetic macular edema that report the intention to capture HRQL outcomes. We have also recommended to investigators to followup on these trials and, if appropriate, to include them in any future systematic reviews of HRQL in patients with diabetic retinopathy or diabetic macular edema.

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Page last reviewed November 2012
Internet Citation: Measuring Health-Related Quality of Life for Patients With Diabetic Re: Disposition of Comments. November 2012. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/research/findings/ta/diabetic-retinopathy.html