This handbook was prepared by Susan L. Norris. Laragh Gollogly and Charles Penn provided advice and support throughout the development process. Contributions in the areas of equity, human rights, gender and social determinants were made in this edition of the handbook (including Chapter 5) by the WHO Gender, Equity and Human Rights mainstreaming team (acknowledged in alphabetical order):#
xi This handbook provides step-by-step guidance on how to plan, develop and publish a World Health Organization (WHO) guideline. It covers the methods, processes and procedures for producing a document that meets WHO standards. It does not provide detailed technical guidance on many of the steps: this can be obtained from the references in the handbook and through references to the published scientific literature listed on WHO's Guideline Review Committee (GRC) intranet site (available to WHO staff). Additional chapters of this handbook containing detailed guidance on selected topics are also available and new chapters will continue to be added to the GRC intranet site in response to the needs of WHO guideline developers.
The first edition of this handbook, published in 2012, provided general guidance on the steps involved in guideline development and on GRC and WHO processes and procedures. This, the second edition, provides additional detailed guidance on each step in guideline development, as well as two additional chapters. Chapter 5 deals with the importance of considering equity, human rights, gender and the social determinants of health in formulating recommendations. The chapter provides specific entry points for integrating these issues into each and every guideline developed by WHO. Chapter 11 describes the development of rapid advice guidelines in the context of a public health emergency, with a focus on how the standard methods of evidence review and synthesis need to be modified to produce such guidelines.
The science underpinning evidence identification and synthesis and the translation of a body of evidence into recommendations continues to evolve. Because of this, any manual on how to produce a guideline requires frequent reassessment and updating. The GRC Secretariat is committed to providing up-to-date guidance that reflects the latest methods and approaches in the peer reviewed literature and the best practices internationally. Feedback on this handbook is welcome: please contact the GRC Secretariat at WHO with comments and suggestions for additional topics for future updates of the handbook or for online dissemination. WHO has adopted internationally recognized methods and standards for guideline development to ensure that its guidelines are of the highest quality. WHO guidelines must be developed in observance of the following principles:  Guidelines address an area of uncertainty and an unmet need for guidance.  Guidelines reflect the core WHO value of the "right to health" (2).  The process of developing recommendations is explicit and transparent: the user can see how and why a recommendation was developed, by whom, and on what basis.  The process of developing guidelines is multidisciplinary and includes all relevant expertise and perspectives, including input from stakeholders.  The processes and methods used in each step of guideline development aim to minimize the risk of bias in the recommendations.  Recommendations are based on a systematic and comprehensive assessment of the balance of a policy's or intervention's potential benefits and harms and explicit consideration of other relevant factors.  The evidence used to develop WHO guidelines is publicly available.  Recommendations can be implemented in, and adapted to, local settings and contexts.  Guidelines should be tailored to a specific audience. (The audiences that WHO guidelines can target include public health policy-makers, health programme managers, health-care providers, patients, caregivers, the general public and other stakeholders.)

# What is the aim of this handbook?
This handbook presents the important principles of guideline development and provides stepwise instruction on the technical and procedural aspects of developing a WHO guideline. It aims to steer readers through the process to ensure that the resulting guideline is credible; the recommendations accurately reflect the balance of potential benefits and harms; the guideline meets WHO's publication standards in terms of content, methods and presentation; the underlying evidence is accessible; and the recommendations are implementable and positive in their impact on population health.

# For whom is this handbook intended?
This handbook is intended for:  any WHO department, programme or staff member wishing to produce a guideline;  members of a WHO guideline steering group;  members of a WHO guideline development group (GDG);  members of a WHO guideline external review group; and  anyone interested in understanding how WHO develops guidelines.

# What is in this handbook?
This handbook follows the entire development of a WHO guideline  from determining if a guideline is needed through to eventual publication. The guideline development process and its primary contributors are summarized in Table 1.1.

# Types of WHO guidelines
It is important to consider what type of guideline will best fit the intended purpose, as this will determine the methods, resources and time frame for development, finalization and dissemination (see Table 1.2). WHO guidelines comprise a broad spectrum of products that vary mainly in terms of the following features:  purpose;  scope;  the point in time at which the guideline is being developed relative to the life-span of an intervention;  the organizations or entities developing the guideline;  the presence in the guideline of new versus previously published recommendations; and  the timeline.
WHO develops four main types of guidelines, defined in terms of the above characteristics: standard, consolidated and interim guidelines, and guidelines produced in response to an emergency or urgent need. In addition, there are other, less frequent types of guidelines.

# Standard guidelines
A standard guideline covers a clinical or policy area (e.g. the treatment of postpartum haemorrhage or the minimum requirements for the safe delivery of care to people with HIV infection). Such guidelines vary greatly in scope and focus: they might address the use of a single drug for a disease or condition, such as naloxone injection by lay persons for suspected opioid overdose, or they might encompass the full scope of a condition or public health problem, such as the diagnosis, screening and treatment of type 2 diabetes mellitus. Recommendations in a standard guideline are either developed de novo or by updating previous WHO guidelines.
Standard guidelines generally focus on one or more of the following:  clinical interventions (e.g. the management of severe acute malnutrition in infants and children);  health-care system or policy approaches (e.g. country pharmaceutical pricing policies);  public health interventions or exposures (e.g. optimal intake of dietary folate in pregnant women);  diagnostic tests (e.g. fluorescent light-emitting diode  microscopy for the diagnosis of tuberculosis), or  surveillance and monitoring (e.g. surveillance guidelines for measles, rubella and congenital rubella syndrome in the WHO European Region).
Standard guidelines usually take between 9 and 24 months to complete, depending on their scope, and should be prepared after wide consultation on their need, scope and rationale. They should be supported by one or more systematic reviews of the evidence and finalized after one or two meetings of the GDG. A standard guideline has to be reviewed by a specified date that will depend on how fast the evidence in the topic area is expected to change. Most WHO guidelines fall into this category.

# Consolidated guidelines
A consolidated guideline (also known as a compilation of guidelines) contains recommendations from existing WHO guidelines, or from guidelines produced by other organizations that have followed processes consistent 7 with those used by WHO (see Section 1.8.2). Producing consolidated guidelines is complex because existing guidelines may need to be updated and new recommendations may have to be added to address important gaps in the existing guidance. In addition, maintaining the document is difficult, since individual recommendations may become outdated at different times. Production times for consolidated guidelines vary widely.
All recommendations contained in a consolidated guideline should be up to date and approved by the WHO Guideline Review Committee (GRC): existing recommendations may need to be updated during preparation of the consolidated guideline. During the updating process, all the standard procedures as outlined in this handbook should be followed. Existing recommendations must be thoroughly, clearly and explicitly cross-referenced.
Consolidated guidelines require review by the GRC if any of the included recommendations were initially published without GRC review; the updating process led to changes in any of the existing recommendations; or new recommendations were developed. A compilation of guidelines that includes recommendations developed by organizations external to WHO must also be reviewed by the GRC. Only consolidated guidelines whose recommendations have all been previously approved by the GRC and have remained unchanged during the updating process do not require review by the GRC.

# Interim guidelines
Interim guidelines are produced when WHO is asked to provide guidance when the available data and information are most certainly incomplete, especially if additional data are anticipated in the near future. This can occur when an intervention  a drug, a medical device or a health practice, for example  has just appeared or is about to be made available; a new disease or condition has emerged; or new data on an existing intervention, exposure, disease or condition have been reported. Interim guidelines usually have a very focused scope and a short shelflife. They should always clearly indicate when additional evidence affecting the interim recommendation(s) is expected to be reported, and thus when an update is anticipated. Although the target audience or other stakeholders may demand that interim guidance be generated quickly, this type of guideline fully complies with all processes and procedures and meets the standards set out in this handbook.

# Guidelines in response to an emergency or urgent need
Certain circumstances preclude the development of a standard guideline. This is the case when WHO must provide guidance in response to public health emergencies. Depending on the type of event or situation, such guidelines may need to be produced within hours, days, weeks or months. Their purpose and the methods used to develop them vary with the time frame in which guidance is required.
Although guidelines that must be produced rapidly cover a wide spectrum, it is convenient to consider two basic types:  Emergency (rapid response) guidelines -Public health emergencies may necessitate a response from WHO within hours to days. Hence, many of the guideline development processes and methods outlined in this handbook are not applicable. WHO staff will need to quickly identify relevant existing guidelines produced by WHO or other entities or may need to issue recommendations based on expert opinion only.
The basic principles of high-quality guidelines, as outlined in Section 1.3, must be adhered to: the recommendations should be applicable to the specified population and setting; the sources for the recommendations must be indicated; to the extent possible, efforts must be made to minimize the risk of bias; and the development process should be explicit and transparent. It may not be feasible to perform a systematic review of all available evidence. However, only sources of high-quality evidence should be used. It is important that the decision-making process be documented and that the rationale for each recommendation be stated, even if it is based on indirect or very limited evidence or on expert opinion. The GRC Secretariat is developing further guidance on this type of guideline.  Rapid advice guidelines -If a public health event continues for an extended period, the initial emergency (rapid response) guidelines must be reviewed to take into account both the evidence emerging from the event and a systematic review of the relevant evidence. Such rapid advice guidelines will follow WHO processes more closely and must meet the standards for guideline development at WHO. These guidelines are published with a review-by date that indicates when the guidance may become invalid, or when it will be updated or converted to a standard guideline. Rapid advice guidelines must be reviewed by the GRC, both at the planning proposal and final guideline stages. Chapter 11 provides detailed guidance on when and how to produce this type of guideline.
For a variety of reasons, WHO may wish to issue recommendations quickly, even in the absence of a public health emergency or continuing urgency. It may choose to do so, for example, when a new drug becomes available, when new information on an existing technology is likely to change existing guidance, or because a Member State or external entity has made an urgent request for guidance. Recommendations issued in such situations must be based on a systematic review and assessment of the evidence and meet all the standards outlined in this handbook, including GRC review at the planning proposal and final guideline stages. However, it may be possible to produce such guidelines within a relatively short time, if the appropriate resources and expertise are available.

# Additional types of guidelines produced by WHO

# Guidelines developed in collaboration with external organizations
Clinical and public health guidelines are produced by many organizations, including national agencies, intergovernmental organizations and specialist medical societies. From time to time it may be appropriate for WHO to collaborate with these groups to produce a joint guideline.
Collaborative guidelines must adhere to the basic principles for WHO guidelines. When developing such guidelines, it is particularly important to note that:  no funding can come from commercial sources, and conflicts of interest must be declared and managed as per WHO procedures;  a systematic review of the relevant evidence is required;  the methods used to develop the recommendations must be explicit and transparent;  the experts who develop the recommendations must adequately represent the guideline's target audience, whether global or regional; and  WHO Press should be consulted on publishing agreements, including matters relating to copyright and open access.
When collaborating with an external organization, WHO may not be able to insist that all WHO processes and procedures for guideline development be followed. WHO staff planning such guidelines need to submit a planning proposal to the GRC describing in detail how the guideline will be developed and highlighting any deviation from the procedures set out in this handbook. The GRC will assess such proposals on a case-by-case basis.

# Guidelines developed by external organizations
Guidelines that serve WHO's purpose may already exist and WHO may consider adopting, adapting or incorporating all or part of a guideline developed by an external organization. In order to adopt or endorse such a guideline, WHO staff in the relevant technical unit must carefully evaluate the guideline's quality and applicability to WHO's needs.
The guideline must meet WHO's standards for guidelines as depicted in this handbook. The two standards that externally developed guidelines can seldom meet are: (a) applicability to a global target audience (most notably low-and middle-income countries); and (b) formulation by a panel of experts with representation from all relevant WHO regions. WHO rarely adopts the recommendations produced by third parties because they fail to comply with these requirements.
A plan for development of a WHO guideline that endorses, adopts or adapts, in whole or in part, a guideline produced by another organization should be submitted to the GRC for assessment, as with any WHO guideline. The planning proposal must include the rationale for selecting that particular guideline; a description of the process used to evaluate its quality, applicability and currency; and the methods and rationale for any revisions (including updating of the evidence and recommendations).

# Adaptation of existing WHO guidelines
WHO guidelines originally intended for one setting may be adapted for use in another. For example, guidelines on routine obstetric care can be adapted for emergency settings. Adaptations of WHO guidelines must follow standard GRC procedures, including GRC review of the planning proposal and the final guideline. Guidelines may also be adapted in emergency or urgent situations, when existing guidelines need to be quickly identified and assessed. The GRC Secretariat is developing further guidance on when and how to adapt existing guidelines in such situations.

# Information products that are not considered guidelines
Certain types of documents are not considered guidelines and do not need to be submitted to the GRC for review. They include:  documents that state established principles (e.g. human rights, WHO constitutional issues);  WHO Secretariat reports and other papers submitted to the Governing Bodies (Executive Board, Regional Committees, World Health Assembly);  information documents that report facts, describe evidence, or document or review existing practices and interventions, provided that such documents are not making recommendations or advocating commitment of resources;  documents containing standards for manufacturing health technologies, such as pharmaceuticals and vaccines;  "how to" documents such as operational manuals (e.g. how to set up a research project or how to implement a service) or implementation guides or tools based on GRC-approved guidelines; and  documents that describe standard operating procedures for organizations or systems.
If you are not sure whether your proposed document is a guideline, please consult with the GRC Secretariat.

# The Guideline Review Committee
The GRC was established by WHO's Director-General in 2007 to ensure that WHO guidelines are of high quality, that they are developed using a transparent and explicit process, and that, to the extent possible, recommendations are based on evidence (3).
The GRC is composed of approximately 30 individuals, including representatives from all WHO regions as well as external members, and meets monthly to review submitted documents.

# Terms of reference of the GRC
All WHO publications containing recommendations must be approved by the GRC according to WHO policies and procedures (4). The GRC reviews every WHO guideline twice during its development -once at the initial planning stage and again after the recommendations have been developed and the guideline document has been finalized and edited.
The review of a planning proposal includes an assessment of whether the proposed guideline development process is consistent with the steps described in this handbook. The review of final submissions ensures that the approved process has been followed and that the final guideline document meets WHO standards as laid out in this handbook, contains clear and actionable recommendations, and meets all WHO reporting requirements. The GRC also provides suggestions and advice on guideline development processes and procedures and on the methods for developing high-quality guidelines at any stage of the development process. The GRC does not provide guidance on the technical content of the guidelines, but rather on how to develop guidelines that will meet WHO standards.
GRC approval is part of WHO's internal clearance processes for the publication of guidelines. The GRC evaluates planning proposals and final guidelines that have been approved by the relevant directors of the technical unit(s) responsible for the document or their regional counterparts, and before clearance of the final guideline by the assistant director-general (ADG) or regional director.
The specific terms of reference for the GRC are to (5):  define appropriate and standardized processes for guideline development at WHO;  ensure that all guidelines published by WHO are of high quality and comply with explicit standards;  develop and implement a plan to ensure that GRC members have the necessary knowledge of the approved methods for guideline development and to identify opportunities to build capacity in guideline development among WHO staff; and  develop collaborations with other organizations and international networks that have methodological expertise and skills in guideline development, adaptation and implementation.

# The GRC Secretariat
The GRC Secretariat has several important roles. In addition to supporting the GRC, it provides WHO staff with technical advice on guideline development, sets benchmarks, and evaluates guideline development processes, documents and standards to achieve quality assurance and improvement for WHO guidelines. More specifically, the GRC Secretariat:  coordinates and provides technical support on guideline development to WHO technical units at headquarters and in the regional offices;  organizes training on guideline development methods and procedures for WHO staff;  provides administrative and technical support for the work of the GRC;  collaborates with other organizations and international networks that provide methodological expertise in guideline development, adaptation and implementation; and  maintains a database of GRC submissions.
Further details on the processes and procedures of the GRC and its Secretariat are found on the WHO GRC intranet site (6). The more planning and thought that goes into guideline development at the beginning, the more efficient the entire process will be and the better the end product. The principles of good project management and high-quality research apply to guideline development. Careful consideration of the issues raised in this chapter and efforts put into developing a thorough and reasoned planning proposal (see Chapter 4) will reduce the time and resources expended on the guideline and result in a superior, more useful final product.