Clinical practice guidelines for the management of neuropathic pain: a systematic review

In the present study, we evaluated the quality of CPGs and consistency of the recommendations of CPGs for the management of NP to assist physicians in the selection of the appropriate recommendations. Our review demonstrated that the overall quality of the CPGs based on the AGREE II instrument was poor. However, we found consistency in the recommendations stated in the 16 CPGs with respect to drug treatment.

The AGREE II instrument allows the evaluation of various aspects of the guidelines, including integrity, reproducibility, and transparency of guidelines among six domains. Each domain has a different value and concern. Domain 1, “Scope and Purpose,” is concerned with the overall aim of the guideline, the specific health questions being addressed, and the target population (items 1–3). Domain 2, “Stakeholder Involvement,” focuses on the extent to which the guideline was developed by the appropriate stakeholders and represents the views of its intended users (items 4–6). Domain 3, “Rigor of Development,” relates to the process used to gather and synthesize the evidence, the methods to formulate the recommendations, and update them (items 7–14). Domain 4, “Clarity of Presentation,” deals with the language, structure, and format of the guideline (items 15–17). Domain 5, “Applicability” pertains to the likely barriers and facilitators to implementation, strategies to improve uptake, and resource implications of applying the guideline (items 18–21). Domain 6, “Editorial Independence” is concerned with the formulation of recommendations not being unduly biased with competing interests (items 22–23).

Our study showed that four domains concerning “Stakeholder Involvement”, “Rigor of Development”, “Applicability”, and “Editorial Independence” had serious shortcomings because the related information was poor provided. The remaining domains, including “Scope and Purpose” and “Clarity of Presentation” tended to more precisely reported because most of the included guidelines described in detail the specific and focused clinical questions they aimed to address, the target population, specific and unambiguous presentation, different management options for different presentations, and easily identifiable presentation.

Although the AGREE II instrument provides six independent domains, the “Rigor of Development” domain is considered the strongest indicator of quality of all the domains because it evaluates the integrity of the guideline development process. Among the included CPGs, low scores in the “Rigor of Development” domain were partly because of poor performance in this aspect, including the literature search and selection methods, lack of external review prior to publication, and lack of guideline updating mechanisms. Among the six domains, the quality of the “Applicability” domain also plays a significant role. A guideline developed systematically with clear recommendations based on the best available evidence could improve the healthcare practice [2]. However, in the present study, most of included guidelines did not describe facilitators and barriers to their application, did not consider the potential resource implications of applying the recommendations, and did not present monitoring or auditing criteria; thus they had a limited effect on improving healthcare quality [2, 27]. Especially for CPGs published by developing regions, treatment recommendations were restricted by the limited availability of resources faced in the respective regions. The “Applicability” domain had a great effect on the implementation of CPGs. Additionally, the “Editorial Independence” domain refers to the most frequent sources of bias in the guidelines, and it was also found to be poor among the CPGs assessed in this study. Although the authors of guidelines might have economic ties with the pharmaceutical industry or even funding from pharmaceutical companies, most guidelines fail to provide information about potential conflicts of interest.

Guidelines need to be evaluated not only for methodological quality but also for validity of their content in terms of recommendations. Thus, this study also analyzed the recommendations of these guidelines for the management of NP. In general, these recommendations were consistent on the diagnosis, assessment and pharmacological management despite scoring poorly in their rigor of development. It was difficult to tell whether we obtained these results because there was insufficient evidence to develop the guidelines or because the CPG authors did not search and make use of the best evidence available.

A large number of the drug development research has been devoted to the field of NP. A large number of analgesic agents have shown efficacy for the treatment of NP. However, no more than 40–60 % of patients have obtained sufficient pain relief with medications alone and in combination [11, 17]. Thus, it should be noted that treatment of patients with NP should be considered an integral component of a more comprehensive approach.

In general, the guidelines for the management of NP vary considerably in terms of quality, because of the apparently low standards. To reduce the variability of the CPGs, guideline development groups should have standard methodology and strategy. Further, it would be helpful to become familiarized with the AGREE II instrument domains to know what information should be reported and how it ought to be reported in the CPGs. Here, we also give some pointers to reduce the variability among the CPGs:

1) The study should describe the specific health question it aims to address, such as prevention, screening, diagnosis, or treatment, and target population, including sex, age clinical condition, severity stage of the disease, comorbidities, and others. 2) The guideline development group should include individuals from all relevant professional groups, not only or mainly health care providers. Competing interests of guideline development group members should be fully recorded and addressed. 3) In the guideline development process, appropriate methodologies and rigorous strategies are important for successful implementation of the resulting recommendations, such as the systematic methods and criteria for selecting the evidence, methods for formulating the recommendations, health benefits, side effects considered in formulating the recommendations, links between the recommendations and the evidence. Additionally, guidelines should be externally reviewed prior to their publication, and a procedure for guideline updating should be planned and described. 4) The different options for the management of the condition or health issue should be clearly presented and the recommendations should be specific and unambiguous. 5) The views of the funding body and interests of the development group should been recorded and addressed.