Patient-Reported Outcome (PRO) Assessment in Clinical Trials: A Systematic Review of Guidance for Trial Protocol Writers

Background

Evidence suggests there are inconsistencies in patient-reported outcome (PRO) assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers.

Methods and Findings

We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013) for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts). 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3%) recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency.

Conclusions

PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information is routinely included in appropriate trial protocols, in order to facilitate rigorous collection/reporting of PRO data, to effectively inform patient care.     

Dissemination Bias in Systematic Reviews of Animal Research: A Systematic Review

Background

Systematic reviews of preclinical studies, in vivo animal experiments in particular, can influence clinical research and thus even clinical care. Dissemination bias, selective dissemination of positive or significant results, is one of the major threats to validity in systematic reviews also in the realm of animal studies. We conducted a systematic review to determine the number of published systematic reviews of animal studies until present, to investigate their methodological features especially with respect to assessment of dissemination bias, and to investigate the citation of preclinical systematic reviews on clinical research.

Methods

Eligible studies for this systematic review constitute systematic reviews that summarize in vivo animal experiments whose results could be interpreted as applicable to clinical care. We systematically searched Ovid Medline, Embase, ToxNet, and ScienceDirect from 1^st January 2009 to 9^th January 2013 for eligible systematic reviews without language restrictions. Furthermore we included articles from two previous systematic reviews by Peters et al. and Korevaar et al.

Results

The literature search and screening process resulted in 512 included full text articles. We found an increasing number of published preclinical systematic reviews over time. The methodological quality of preclinical systematic reviews was low. The majority of preclinical systematic reviews did not assess methodological quality of the included studies (71%), nor did they assess heterogeneity (81%) or dissemination bias (87%). Statistics quantifying the importance of clinical research citing systematic reviews of animal studies showed that clinical studies referred to the preclinical research mainly to justify their study or a future study (76%).

Discussion

Preclinical systematic reviews may have an influence on clinical research but their methodological quality frequently remains low. Therefore, systematic reviews of animal research should be critically appraised before translating them to a clinical context.     

Assisted Knowledge Discovery for the Maintenance of Clinical Guidelines

Background

Improving antibiotic prescribing practices is an important public-health priority given the widespread antimicrobial resistance. Establishing clinical practice guidelines is crucial to this effort, but their development is a complex task and their quality is directly related to the methodology and source of knowledge used.

Objective

We present the design and the evaluation of a tool (KART) that aims to facilitate the creation and maintenance of clinical practice guidelines based on information retrieval techniques.

Methods

KART consists of three main modules 1) a literature-based medical knowledge extraction module, which is built upon a specialized question-answering engine; 2) a module to normalize clinical recommendations based on automatic text categorizers; and 3) a module to manage clinical knowledge, which formalizes and stores clinical recommendations for further use. The evaluation of the usability and utility of KART followed the methodology of the cognitive walkthrough.

Results

KART was designed and implemented as a standalone web application. The quantitative evaluation of the medical knowledge extraction module showed that 53% of the clinical recommendations generated by KART are consistent with existing clinical guidelines. The user-based evaluation confirmed this result by showing that KART was able to find a relevant antibiotic for half of the clinical scenarios tested. The automatic normalization of the recommendation produced mixed results among end-users.

Conclusions

We have developed an innovative approach for the process of clinical guidelines development and maintenance in a context where available knowledge is increasing at a rate that cannot be sustained by humans. In contrast to existing knowledge authoring tools, KART not only provides assistance to normalize, formalize and store clinical recommendations, but also aims to facilitate knowledge building.     

Economic Evaluation of Active Implementation versus Guideline Dissemination for Evidence-Based Care of Acute Low-Back Pain in a General Practice Setting

Introduction

The development and publication of clinical practice guidelines for acute low-back pain has resulted in evidence-based recommendations that have the potential to improve the quality and safety of care for acute low-back pain. Development and dissemination of guidelines may not, however, be sufficient to produce improvements in clinical practice; further investment in active implementation of guideline recommendations may be required. Further research is required to quantify the trade-off between the additional upfront cost of active implementation of guideline recommendations for low-back pain and any resulting improvements in clinical practice.

Methods

Cost-effectiveness analysis alongside the IMPLEMENT trial from a health sector perspective to compare active implementation of guideline recommendations via the IMPLEMENT intervention (plus standard dissemination) against standard dissemination alone.

Results

The base-case analysis suggests that delivery of the IMPLEMENT intervention dominates standard dissemination (less costly and more effective), yielding savings of $135 per x-ray referral avoided (-$462.93/3.43). However, confidence intervals around point estimates for the primary outcome suggest that – irrespective of willingness to pay (WTP) – we cannot be at least 95% confident that the IMPLEMENT intervention differs in value from standard dissemination.

Conclusions

Our findings demonstrate that moving beyond development and dissemination to active implementation entails a significant additional upfront investment that may not be offset by health gains and/or reductions in health service utilization of sufficient magnitude to render active implementation cost-effective.     

Publication bias in laboratory animal research: a survey on magnitude, drivers, consequences and potential solutions

Context

Publication bias jeopardizes evidence-based medicine, mainly through biased literature syntheses. Publication bias may also affect laboratory animal research, but evidence is scarce.

Objectives

To assess the opinion of laboratory animal researchers on the magnitude, drivers, consequences and potential solutions for publication bias. And to explore the impact of size of the animals used, seniority of the respondent, working in a for-profit organization and type of research (fundamental, pre-clinical, or both) on those opinions.

Design

Internet-based survey.

Setting

All animal laboratories in The Netherlands.

Participants

Laboratory animal researchers.

Main Outcome Measure(s)

Median (interquartile ranges) strengths of beliefs on 5 and 10-point scales (1: totally unimportant to 5 or 10: extremely important).

Results

Overall, 454 researchers participated. They considered publication bias a problem in animal research (7 (5 to 8)) and thought that about 50% (32–70) of animal experiments are published. Employees (n = 21) of for-profit organizations estimated that 10% (5 to 50) are published. Lack of statistical significance (4 (4 to 5)), technical problems (4 (3 to 4)), supervisors (4 (3 to 5)) and peer reviewers (4 (3 to 5)) were considered important reasons for non-publication (all on 5-point scales). Respondents thought that mandatory publication of study protocols and results, or the reasons why no results were obtained, may increase scientific progress but expected increased bureaucracy. These opinions did not depend on size of the animal used, seniority of the respondent or type of research.

Conclusions

Non-publication of “negative” results appears to be prevalent in laboratory animal research. If statistical significance is indeed a main driver of publication, the collective literature on animal experimentation will be biased. This will impede the performance of valid literature syntheses. Effective, yet efficient systems should be explored to counteract selective reporting of laboratory animal research.     

Genetic substructure in cynomolgus macaques (Macaca fascicularis) on the island of Mauritius

Background

Nonhuman primates are commonly used in biomedical research as animal models of human disease and behavior. Compared to common rodent models, nonhuman primates are genetically, physiologically, behaviorally and neurologically more similar to humans owing to more recent shared ancestry and therefore provide the advantage of greater translational validity in preclinical studies. The cynomolgus macaque (Macaca fascicularis) is one of the most commonly used nonhuman primates in academic and industry settings, yet population genetic research has revealed significant substructure throughout the species distribution that may confound studies. Cynomolgus monkeys introduced to Mauritius specifically have previously been thought to maintain the least genetic heterogeneity of all cynomolgus monkeys, although recent work, including work from our lab, suggests macaques from Mauritius too may harbor cryptic substructure.

Results

To evaluate putative substructure in Mauritian cynomolgus macaques, we designed a panel of 96 single nucleotide polymorphisms based on preliminary findings from previous work to screen 246 of cynomolgus monkeys from two primary suppliers. Results from this study support substructure in Mauritian macaques and suggest a minimum of two populations and maybe three on Mauritius, with moderate admixture.

Conclusion

These findings inform the natural history of these monkeys suggesting either a previously unrecognized physical or ecological barrier to gene flow on Mauritius and/or the breakdown of historic substructure resulting from the history of macaque introduction to the island. These findings are relevant to ongoing research using these models in part because of increased appreciation of segregating common variation with functional effects and may be used to better inform animal selection in preclinical research.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-748) contains supplementary material, which is available to authorized users.     

Guidelines on chemotherapy in advanced stage gynecological malignancies: an evaluation of 224 professional societies and organizations

Background

Clinical practice guidelines are important for guiding practice, but it is unclear if they are commensurate with the available evidence.

Methods

We examined guidelines produced by cancer and gynecological societies and organizations and evaluated their coverage of and stance towards chemotherapy for advanced stage disease among 4 gynecological malignancies (breast, ovarian, cervical, endometrial cancer) where the evidence for the use of chemotherapy is very different (substantial and conclusive for breast and ovarian cancer, limited and suggesting no major benefit for cervical and endometrial cancer). Eligible societies and organizations were identified through systematic internet searches (last update June 2009). Pertinent websites were scrutinized for presence of clinical practice guidelines, and relative guidelines were analyzed.

Results

Among 224 identified eligible societies and organizations, 69 (31%) provided any sort of guidelines, while recommendations for chemotherapy on advanced stage gynecological malignancies were available in 20 of them. Only 14 had developed their own guideline, and only 5 had developed guidelines for all 4 malignancies. Use of levels of evidence and grades of recommendations, and aspects of the production, implementation, and timeliness of the guidelines did not differ significantly across malignancies. Guidelines on breast and ovarian cancer utilized significantly more randomized trials and meta-analyses. Guidelines differed across malignancies on their coverage of disease-free survival (p = 0.033), response rates (p = 0.024), symptoms relief (p = 0.005), quality of life (p = 0.001) and toxicity (p = 0.039), with breast and ovarian cancer guidelines typically covering more frequently these outcomes. All guidelines explicitly or implicitly endorsed the use of chemotherapy.

Conclusions

Clinical practice guidelines are provided by the minority of professional societies and organizations. Available guidelines tend to recommend chemotherapy even for diseases where the effect of chemotherapy is controversial and recommendations are based on scant evidence.     

Who Has Used Internal Company Documents for Biomedical and Public Health Research and Where Did They Find Them?

Objective

To describe the sources of internal company documents used in public health and healthcare research.

Methods

We searched PubMed and Embase for articles using internal company documents to address a research question about a health-related topic. Our primary interest was where authors obtained internal company documents for their research. We also extracted information on type of company, type of research question, type of internal documents, and funding source.

Results

Our searches identified 9,305 citations of which 357 were eligible. Scanning of reference lists and consultation with colleagues identified 4 additional articles, resulting in 361 included articles. Most articles examined internal tobacco company documents (325/361; 90%). Articles using documents from pharmaceutical companies (20/361; 6%) were the next most common. Tobacco articles used documents from repositories; pharmaceutical documents were from a range of sources. Most included articles relied upon internal company documents obtained through litigation (350/361; 97%). The research questions posed were primarily about company strategies to promote or position the company and its products (326/361; 90%). Most articles (346/361; 96%) used information from miscellaneous documents such as memos or letters, or from unspecified types of documents. When explicit information about study funding was provided (290/361 articles), the most common source was the US-based National Cancer Institute. We developed an alternative and more sensitive search targeted at identifying additional research articles using internal pharmaceutical company documents, but the search retrieved an impractical number of citations for review.

Conclusions

Internal company documents provide an excellent source of information on health topics (e.g., corporate behavior, study data) exemplified by articles based on tobacco industry documents. Pharmaceutical and other industry documents appear to have been less used for research, indicating a need for funding for this type of research and well-indexed and curated repositories to provide researchers with ready access to the documents.     

Reporting of Quantitative Protein Electrophoresis in Australia and New Zealand: a Call for Standardisation

Background

The lack of guidelines on reporting standards for protein electrophoresis may have led to significant differences in reports from different laboratories.

Objective

To determine the extent of variation in reporting of protein electrophoresis results in Australia and New Zealand.

Method

Questionnaires were distributed to laboratories throughout Australia and New Zealand asking about protein electrophoresis practices and reporting.

Results

Extensive variation was found in the following reporting practices: (a) units for urine Bence Jones protein (BJP); (b) reporting absence of a paraprotein rather than a normal pattern; (c) numerical reporting of all protein fractions or only the paraprotein; (d) warning of possible inaccuracy in the serum immunoglobulin result of the paraprotein type; (e) co-migration of a paraprotein with a normal serum protein; (f) use of a confirmatory test when a known paraprotein is no longer detectable.

Conclusions

A working party should be established to make recommendations on the reporting of protein electrophoresis. Implementation of such recommendations should reduce both report variation between laboratories and the risk of misinterpretation of reports.     

Adherence by Dutch Public Health Nurses to the National Guidelines for Tuberculosis Contact Investigation

Objectives

To assess whether public health nurses adhered to Dutch guidelines for tuberculosis contact investigations and to explore which factors influenced the process of identifying contacts, prioritizing contacts for testing and scaling up a contact investigation.

Methods

A multiple-case study (2010–2012) compared the contact investigation guidelines as recommended with their use in practice. We interviewed twice 14 public health nurses of seven Public Health Services while they conducted a contact investigation.

Results

We found more individuals to be identified as contacts than recommended, owing to a desire to gain insight into the infectiousness of the index case and prevent anxiety among potential contacts. Because some public health nurses did not believe the recommendations for prioritizing contacts fully encompassed daily practice, they preferred their own regular routine. In scaling up a contact investigation, they hardly applied the stone-in-the-pond principle. They neither regularly compared the infection prevalence in the contact investigation with the background prevalence in the community, especially not in immigrant populations. Nonadherence was related to ambiguity of the recommendations and a tendency to act from an individual health-care position rather than a population health perspective.

Conclusions

The adherence to the contact investigation guidelines was limited, restraining the effectiveness, efficiency and uniformity of tuberculosis control. Adherence could be optimized by specifying guideline recommendations, actively involving the TB workforce, and training public health nurses.     

A Systematic Review of Recent Clinical Practice Guidelines on the Diagnosis,Assessment and Management of Hypertension

Background

Despite the availability of clinical practice guidelines (CPGs), optimal hypertension control is not achieved in many parts of the world; one of the challenges is the volume of guidelines on this topic and their variable quality. To systematically review the quality, methodology, and consistency of recommendations of recently-developed national CPGs on the diagnosis, assessment and the management of hypertension.

Methodology/Principal Findings

MEDLINE, EMBASE, guidelines'' websites and Google were searched for CPGs written in English on the general management of hypertension in any clinical setting published between January 2006 and September 2011. Four raters independently appraised each CPG using the AGREE-II instrument and 2 reviewers independently extracted the data. Conflicts were resolved by discussion or the involvement of an additional reviewer. Eleven CPGs were identified. The overall quality ranged from 2.5 to 6 out of 7 on the AGREE-II tool. The highest scores were for “clarity of presentation” (44.4% −88.9%) and the lowest were for “rigour of development” (8.3%–30% for 9 CGPs). None of them clearly reported being newly developed or adapted. Only one reported having a patient representative in its development team. Systematic reviews were not consistently used and only 2 up-to-date Cochrane reviews were cited. Two CPGs graded some recommendations and related that to levels (but not quality) of evidence. The CPGs'' recommendations on assessment and non-pharmacological management were fairly consistent. Guidelines varied in the selection of first-line treatment, adjustment of therapy and drug combinations. Important specific aspects of care (e.g. resistant hypertension) were ignored by 6/11 CPGs. The CPGs varied in methodological quality, suggesting that their implementation might not result in less variation of care or in better health-related outcomes.

Conclusions/Significance

More efforts are needed to promote the realistic approach of localization or local adaptation of existing high-quality CPGs to the national context.     

Quality of Clinical Practice Guidelines for Glycemic Control in Type 2 Diabetes Mellitus

Background

Several studies have reported that clinical practice guidelines (CPGs) in a variety of clinical areas are of modest or variable quality. The objective of this study was to evaluate the quality of an international cohort of CPGs that provide recommendations on pharmaceutical management of glycemic control in patients with type 2 diabetes mellitus (DM2).

Methods and Findings

We searched the National Guideline Clearinghouse (NGC) on February 15th and June 4th, 2012 for CPGs meeting inclusion criteria. Two independent assessors rated the quality of each CPG using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument. Twenty-four guidelines were evaluated, and most had high scores for clarity and presentation. However, scope and purpose, stakeholder involvement, rigor of development, and applicability domains varied considerably. The majority of guidelines scored low on editorial independence, and only seven CPGs were based on an underlying systematic review of the evidence.

Conclusions

The overall quality of CPGs for glycemic control in DM2 is moderate, but there is substantial variability among quality domains within and across guidelines. Guideline users need to be aware of this variability and carefully appraise and select the guidelines that they apply to patient care.     

Weight-Loss Strategies Used by the General Population: How Are They Perceived?

Background

The rising prevalence of obesity and the social pressure for thinness increase the prevalence of dieting. However, little is known about the overall perception of dieting strategies actually used by the general population.

Objectives

Our main objective was to investigate perceptions of weight-loss practices in an observational study in order to identify the most favourable strategy.

Design

Adults from the ongoing Nutrinet-Santé cohort study who had reported engaging in dieting in the three previous years were included in the study. For each diet, detailed information was collected on types of diets, circumstances and perception of the diet, and outcomes. Perceptions were compared across diets using sex-specific mixed effects models.

Result

Among the 48 435 subjects who had completed the respective questionnaire, 12 673 (26.7%, 87.8% of women) had followed at least one weight-loss diet in the previous three years. Diet plans prescribed by health professionals and diets conforming to official dietary recommendations were the most favourably perceived among all assessed weight-loss strategies. Alternatively, commercial diet plans and self-imposed dietary restrictions were more negatively perceived (Odds ratios (OR) for adherence difficulty 1.30 (95% confidence interval (0.99;1.7)) in men and OR 1.92 (1.76;2.10) in women compared to official nutritional guidelines; OR 1.06 (0.82;1.38) in men and OR 1.39 (1.26;1.54) in women respectively) compared to official nutritional guidelines.

Conclusion

Official dietary recommendations could be useful tools for maintaining a dietary balance while following a weight-loss diet.     

A Systematic Review of Scope and Quality of Health Economic Evaluation Studies in Vietnam

Introduction

The application of health economic evaluation (HEE) evidence can play an important role in strategic planning and policy making. This study aimed to assess the scope and quality of existing research, with the goal of elucidating implications for improving the use of HEE evidence in Vietnam.

Methods

A comprehensive search strategy was developed to search medical online databases (Medline, Google Scholar, and Vietnam Medical Databases) to select all types of HEE studies except cost-only analyses. Two researchers assessed the quality of selected studies using the Quality of Health Economic Studies (QHES) instrument.

Results

We selected 26 studies, including 6 published in Vietnam. The majority of these studies focused on infectious diseases (14 studies), with HIV being the most common topic (5 studies). Most papers were cost-effectiveness studies that measured health outcomes using DALY units. Using QHES, we found that the overall quality of HEE studies published internationally was much higher (mean score 88.7+13.3) than that of those published in Vietnam (mean score 67.3+22.9). Lack of costing perspectives, reliable data sources and sensitivity analysis were the main shortcomings of the reviewed studies.

Conclusion

This review indicates that HEE studies published in Vietnam are limited in scope and number, as well as by several important technical errors or omissions. It is necessary to formalize the process of health economic research in Vietnam and to institutionalize the links between researchers and policy-makers. Additionally, the quality of HEE should be enhanced through education about research techniques, and the implementation of standard HEE guidelines.     

Biochemical Parameters for Longitudinal Monitoring of Liver Function in Rat Models of Partial Hepatectomy Following Liver Injury

Background

While evaluation of liver function in preclinical animal studies is commonly performed at selected time-points by invasive determination of the liver/body weight ratio and histological analyses, the validation of longitudinal measurement tools for monitoring liver function are of major interest.

Aims

To longitudinally evaluate serum cholinesterase (CHE) and total serum bilirubin (TSB) levels as non-invasive markers to determine injury- and partial hepatectomy (PHx)-induced alterations of liver function in rats.

Methods

Male and female Lewis rats were subjected to either methionine/choline deficient (MCD) diet or treatment with FOLFOX chemotherapy prior to PHx. Body weight and CHE/TSB levels are determined weekly. Following PHx and at the study end, histological analyses of liver tissue are performed.

Results

Following MCD diet, but not after FOLFOX chemotherapy treatment, results indicate gender-specific alterations in serum CHE levels and gender-independent alterations in TSB levels. Likewise, histological analyses of resected liver parts indicate significant liver injury following MCD-diet, but not following FOLFOX treatment. While TSB levels rapidly recover following MCD diet/FOLFOX treatment combined with a PHx, serum CHE levels are subject to significant model- and gender-specific differences, despite full histopathological recovery of liver tissue.

Conclusions

Longitudinal measurements of serum CHE levels and TSB levels in rats are highly complementary as non-invasive parameters for evaluation of liver injury and/or recovery.     

Predicting the lay preventive strategies in response to avian influenza from perceptions of the threat

Background

The identification of patterns of behaviors that lay people would engage in to protect themselves from the risk of infection in the case of avian influenza outbreak, as well as the lay perceptions of the threat that underlie these risk reduction strategies.

Methodology/Principal Findings

A population-based survey (N = 1003) was conducted in 2008 to understand and describe how the French public might respond to a possible outbreak. Factor analyses highlighted three main categories of risk reduction strategies consisting of food quality assurance, food avoidance, and animal avoidance. In combination with the fear of contracting avian influenza, mental representations associated with the manifestation and/or transmission of the disease were found to significantly and systematically shape the behavioral responses to the perceived threat.

Conclusions/Significance

This survey provides insight into the nature and predictors of the protective patterns that might be expected from the general public during a novel domestic outbreak of avian influenza.     

Conflict of interest in clinical practice guideline development: a systematic review

Background

There is an emerging literature on the existence and effect of industry relationships on physician and researcher behavior. Much less is known, however, about the effects of these relationships and other conflicts of interest (COI) on clinical practice guideline (CPG) development and recommendations. We performed a systematic review of the prevalence of COI and its effect on CPG recommendations.

Methodology/Principal Findings

We searched Medline (1980 to March, 2011) for studies that examined the effect of COI on CPG development and/or recommendations. Data synthesis was qualitative. Twelve studies fulfilled inclusion criteria; 9 were conducted in the US. All studies reported on financial relationships of CPG authors with the pharmaceutical industry; 1 study also examined relationships with diagnostic testing and insurance companies. The majority of guidelines had authors with industry affiliations, including consultancies (authors with relationship, range 6–80%); research support (4–78%); equity/stock ownership (2–17%); or any COI (56–87%). Four studies reported multiple types of financial interactions for individual authors (number of types per author: range 2 to 10 or more). Data on the effect of COI on CPG recommendations were confined to case studies wherein authors with specific financial ties appeared to benefit from the related CPG recommendations. In a single study, few authors believed that their relationships influenced their recommendations. No studies reported on intellectual COI in CPGs.

Conclusions/Significance

There are limited data describing the high prevalence of COI among CPG authors, and only case studies of the effect of COI on CPG recommendations. Further research is needed to explore this potential source of bias.     

Guideline Compliance in Chronic Heart Failure Patients with Multiple Comorbid Diseases: Evaluation of an Individualised Multidisciplinary Model of Care

Objective

To assess the impact of individualised, reconciled evidence-based recommendations (IRERs) and multidisciplinary care in patients with chronic heart failure (CHF) on clinical guideline compliance for CHF and common comorbid conditions.

Design and setting

A retrospective hospital clinical audit conducted between 1^st July 2006 and February 2011.

Participants

A total of 255 patients with a diagnosis of CHF who attended the Multidisciplinary Ambulatory Consulting Services (MACS) clinics, at the Royal Adelaide Hospital, were included.

Main outcome measures

Compliance with Australian clinical guideline recommendations for CHF, atrial fibrillation, diabetes mellitus and ischaemic heart disease.

Results

Study participants had a median of eight medical conditions (IQR 6–10) and were on an average of 10 (±4) unique medications. Compliance with clinical guideline recommendations for pharmacological therapy for CHF, comorbid atrial fibrillation, diabetes or ischaemic heart disease was high, ranging from 86% for lipid lowering therapy to 98% anti-platelet agents. For all conditions, compliance with lifestyle recommendations was lower than pharmacological therapy, ranging from no podiatry reviews for CHF patients with comorbid diabetes to 75% for heart failure education. Concordance with many guideline recommendations was significantly associated if the patient had IRERs determined, a greater number of recommendations, more clinic visits or if patients participated in a heart failure program.

Conclusions

Despite the high number of comorbid conditions and resulting complexity of the management, high compliance to clinical guideline recommendations was associated with IRER determination in older patients with CHF. Importantly these recommendations need to be communicated to the patient’s general practitioner, regularly monitored and adjusted at clinic visits.     

Current guidelines have limited applicability to patients with comorbid conditions: a systematic analysis of evidence-based guidelines

Background

Guidelines traditionally focus on the diagnosis and treatment of single diseases. As almost half of the patients with a chronic disease have more than one disease, the applicability of guidelines may be limited. The aim of this study was to assess the extent that guidelines address comorbidity and to assess the supporting evidence of recommendations related to comorbidity.

Methodology/Principal Findings

We conducted a systematic analysis of evidence-based guidelines focusing on four highly prevalent chronic conditions with a high impact on quality of life: chronic obstructive pulmonary disease, depressive disorder, diabetes mellitus type 2, and osteoarthritis. Data were abstracted from each guideline on the extent that comorbidity was addressed (general comments, specific recommendations), the type of comorbidity discussed (concordant, discordant), and the supporting evidence of the comorbidity-related recommendations (level of evidence, translation of evidence). Of the 20 guidelines, 17 (85%) addressed the issue of comorbidity and 14 (70%) provided specific recommendations on comorbidity. In general, the guidelines included few recommendations on patients with comorbidity (mean 3 recommendations per guideline, range 0 to 26). Of the 59 comorbidity-related recommendations provided, 46 (78%) addressed concordant comorbidities, 8 (14%) discordant comorbidities, and for 5 (8%) the type of comorbidity was not specified. The strength of the supporting evidence was moderate for 25% (15/59) and low for 37% (22/59) of the recommendations. In addition, for 73% (43/59) of the recommendations the evidence was not adequately translated into the guidelines.

Conclusions/Significance

Our study showed that the applicability of current evidence-based guidelines to patients with comorbid conditions is limited. Most guidelines do not provide explicit guidance on treatment of patients with comorbidity, particularly for discordant combinations. Guidelines should be more explicit about the applicability of their recommendations to patients with comorbidity. Future clinical trials should also include patients with the most prevalent combinations of chronic conditions.