Recruitment of Technical Experts and Peer Reviewers

Experts were sought who could provide content and/or methodological guidance. The five technical experts were chosen to cover several domains: hypertension management, SMBP, ABP, clinic BP, and evaluation of screening and diagnostic tests. Input was sought from the partner and technical experts through ad hoc correspondence as well as through more formal requests for feedback during the project. Specific requests for feedback were made for key decisions, such as selection and refinement of the questions.

Comprehensive feedback on the draft report was sought from the partner, the technical experts, and other reviewers. Reviewers included members of the NHBPEP Coordinating Committee selected through discussions with the partner. (See appendix A for list of organizations represented by reviewers from which comments were received.)

Patient Population

The search was not limited by age, gender or any other patient characteristic. However, because of the extensive volume of literature, the review did not synthesize evidence for all types of populations. For instance, it was felt that the use of blood pressure monitoring during pregnancy was a distinctive application of these technologies that was beyond the scope of this report. Likewise, articles that focused exclusively on populations of children (less than 20 years of age) were not reviewed.

Questions

The original questions provided by AHRQ included several descriptive questions that were more appropriately addressed as background text in Chapter 1. The EPC team refined the remaining questions and requested feedback from the technical experts and from the partner. When the large volume and heterogeneity of the literature became apparent, the EPC team refined the questions further. Listed below are the questions addressed in this report.

• Comparison of clinic, ambulatory, and SMBP readings:
      1a. What is the distribution of the BP differences between clinic, ambulatory and SMBP readings? If there are differences, are these differences reproducible?
      2a. What is the prevalence of WCH as defined by SMBP? Is this pattern reproducible?
      3a. What is the prevalence of WCH as defined by ABP measurement? Is this pattern reproducible?
• SMBP levels and WCH based on SMBP as related to clinical outcomes:
      2a. Is SMBP more or less strongly associated with BP-related target organ damage than clinic BP measurements?
      2b. Does SMBP predict subsequent clinical outcomes?
      2c. What is the incremental gain in prediction of clinical outcomes from use of self-measurement devices beyond prediction from clinic BP alone?
      2d. What is the effect of treatment guided by SMBP in comparison to treatment guided by clinic BP, in terms of:
  

  1. BP-related target organ damage
  2. symptoms
  3. use of anti-hypertensive drug therapy
  4. BP control
• ABP levels and WCH based on ABP as related to clinical outcomes:
      3a. Is ambulatory blood pressure more or less strongly associated with BP-related target organ damage than clinic BP measurements?
      3b. Does ambulatory blood pressure predict subsequent clinical outcomes?
      3c. What is the incremental gain in prediction of clinical outcomes from use of ambulatory devices beyond prediction from clinic BP alone?
      3d. What is the effect of treatment guided by ABP in comparison to treatment guided by clinic BP, in terms of:
  

  1. BP-related target organ damage
  2. symptoms
  3. use of anti-hypertensive drug therapy
  4. BP control
• Does the evidence for the above questions vary according to a patient's age, gender, income level, race/ethnicity, and clinical subgroups (e.g., hypertensive/normotensive, diabetic, renal transplant status)?

Causal Pathway

During its deliberations, the EPC team developed a conceptual framework to assist in the formulation of its research questions. (See Figure 1.) It is evident that several factors might influence the use and interpretation of BP measurements, including patient factors (age, race, gender, clinical conditions), technical factors (accuracy, reproducibility, operator, machine), other CVD risk factors, and response to treatment. Also, there are many potential outcomes of interest including clinical events (CHD, stroke, kidney disease), BP control, cost, side effects, and medication. The EPC team had sufficient resources to address several key points in this pathway (e.g., prognosis) but not all steps (e.g., assessment of device accuracy) or outcomes (e.g., cost). This pathway can also be used as a conceptual framework to identify gaps in the evidence.

Figure

Figure 1. Conceptual Framework.

Literature Search Methods

Searching the literature included the steps of identifying reference sources, formulating a search strategy for each source, and executing and documenting each search.

Abstract Review

Specific inclusion and exclusion criteria were applied at each of three levels of review, with criteria becoming more stringent as the process moved from searching, to the review of abstracts and to the review of articles. After identifying a citation, its title and abstract were reviewed, and articles were included or excluded from the article review on this basis.

Article Review

The purpose of the article review was to confirm relevance of each article to the research questions, to determine methodological characteristics pertaining to study quality, and to collect evidence that addressed the research questions. Where articles described more than one study, reviewers were instructed to complete the eligibility assessment (i.e., comparison to inclusion and exclusion criteria), quality assessment and data abstraction for each study separately. For each question, publications of the same information from the same study were also excluded. These apparent duplicate publications were reviewed on a per case basis. Multiple publications were kept if they reported on different results (i.e., different outcomes). Otherwise, the article with a more comprehensive reporting of the data reviewed.

Because of the large number of citations that remained eligible for full article review even after the second level abstract review, additional exclusion criteria were applied at the article review level. The final full list of exclusion criteria differed by question.

Exclusion criteria applied to all articles during article review:

• does not include human data
• not in English
• no original data
• meeting abstract (no full article for review)
• article does not apply to any of the research questions
• article does not include ambulatory or self-measured blood pressure
• article included <50 patients OR addressed reproducibility and included <20 patients
• device evaluation was the primary purpose of the study
• study population is exclusively pregnant women
• study population is exclusively children (<20 years of age)
• article addresses research question, but does not present data in an abstractable format
• article addresses only the prevalence of dipping versus non-dipping and no other research questions

Additional exclusion criteria for articles addressing question #1:

• article provided data for clinic blood pressure AND ambulatory blood pressure, or clinic blood pressure AND self-measured blood pressure but did not include a formal within-person comparison of measurements (e.g., no p-value, standard error, standard deviation, confidence intervals or only correlation coefficient(s) provided)
• clinic blood pressure measurement used in analyses was completed on one day only
  The criterion of more than one day of measurement for clinic blood pressure was added because an average clinic blood pressure based on just one day of measurements (typically just one to three readings) is extremely imprecise and could lead to a biased comparison with ambulatory or self-measured blood pressure. This criterion was not applied to articles addressing questions 2-4.

For articles addressing questions #2a and #3a, the following specific exclusion criteria were applied:

• article described cross-sectional/retrospective study and did not include comparison with clinic measurement
• article described cross-sectional study but outcome was not left ventricular mass (by echocardiography) or proteinuria/albuminuria

Several endpoints were considered to compare the ability of clinic, self-measured, and ABP monitoring to assess target organ damage caused by hypertension. Left ventricular mass and protein/albumin excretion were included in the report because they are frequently used in the clinic setting to assess the severity and prognosis of hypertension, they are frequently used in hypertension research studies, and there are standard methods available that may allow for some comparability across studies. Other echocardiographic indices of left ventricular enlargement, such as septal thickness or posterior wall thickness, are not consistently reported, and were not considered in this report. Other markers of target organ damage, such as other echocardiographic determinations of left ventricular function, retinopathy, brain MRI findings, carotid intima-media thickness, were not considered in this report.

Because a relatively small number of articles were expected and the abstraction would be quite different, prospective studies (questions #2b or #3b), studies of reproducibility (question #1 a, b, c) and trials examining the impact of treatment guided by clinic versus that guided by ambulatory (question #3d) or self-measurement (question #2d), were tagged during the initial article review. A separate review was then completed for each of these questions including the following additional or modified exclusion criteria.

For articles addressing reproducibility (#1 a, b, c) the additional or modified exclusion criteria were:

• article included < 20 patients
• article does not include reproducibility of white-coat hypertension.

An initial review of articles did not identify any articles addressing reproducibility of the differences between clinic, ambulatory and/or self blood pressure measurements (question #1a). A separate review form for this question was, therefore, not developed. However, the review form used for articles addressing reproducibility was designed to identify articles addressing reproducibility of differences for future consideration.

Additional exclusion criteria for prospective or longitudinal studies (question #2b or #3b) was outcome not of interest.

For articles concerning effect of treatment guided by ambulatory or self measured blood pressure (question #2d or #3d), the additional criterion applied was non-random allocation of participants.

Peer Review

Throughout the project, feedback was sought from the technical experts through ad hoc and formal requests for guidance. A draft of the completed report was sent to the technical experts, as well as to the partner, AHRQ, and other peer reviewers. Substantive comments were entered into a database. Revisions were made to the evidence report, as warranted, and a summary of the comments and their disposition was submitted to AHRQ with the final report.