Methods of Development of Evidence-Based Guidelines

Administration

The ATA Executive Council and the Executive Committee of AACE forged an agreement outlining the working relationship between the two groups surrounding the development and dissemination of management guidelines for the treatment of patients with thyrotoxicosis. A chairperson was selected to lead the task force and this individual (R.S.B.) identified the other 11 members of the panel in consultation with the ATA and the AACE boards of directors. Membership on the panel was based on clinical expertise, scholarly approach, and representation of adult and pediatric endocrinology, nuclear medicine, and surgery. The task force included individuals from both North America and Europe. In addition, the group recruited an expert on the development of evidence-based guidelines (V.M.M.) to serve in an advisory capacity. Panel members declared whether they had any potential conflict of interest at the initial meeting of the group and periodically during the course of deliberations. Funding for the guidelines was derived solely from the general funds of the ATA and thus the task force functioned without commercial support.

To develop a scholarly and useful document, the task force first developed a list of the most common causes of thyrotoxicosis and the most important questions that a practitioner might pose when caring for a patient with a particular form of thyrotoxicosis or special clinical condition. Two task force members were assigned to review the literature relevant to each of the topics, using a systematic PubMed search for primary references and reviews supplemented with additional published materials available before June 2010, and develop recommendations based on the literature and expert opinion where appropriate. A preliminary document and a series of recommendations concerning all of the topics were generated by each subgroup and then critically reviewed by the task force at large. The panel agreed recommendations would be based on consensus of the panel and that voting would be used if agreement could not be reached. Two recommendations were not unanimous and the dissenting position is noted. Task force deliberations took place during several lengthy committee meetings, multiple telephone conference calls, and through electronic communication.

TABLE 1. GRADING OF RECOMMENDATIONS, ASSESSMENT, DEVELOPMENT, AND EVALUATION SYSTEM

Type of grading

Definition of grades

Strength of the recommendation

1 = strong recommendation (for or against)

 

Applies to most patients in most circumstances

 

Benefits clearly outweigh the risk (or vice versa)

 

2 = weak recommendation (for or against)

 

Best action may differ depending on circumstances or patient values

 

Benefits and risks or burdens are closely balanced, or uncertain

Quality of the evidence

+ + + = High quality; evidence at low risk of bias, such as high quality randomized trials showing consistent results directly applicable to the recommendation

 

 + + = Moderate quality; studies with methodological flaws, showing inconsistent or indirect evidence

 

+ = Low quality; case series or unsystematic clinical observations

 Rating of the recommendations

These guidelines were developed to combine the best scientific evidence with the experience of seasoned clinicians and the pragmatic realities inherent in implementation. The task force elected to rate the recommendations according to the system developed by the Grading of Recommendations, Assessment, Development, and Evaluation Group (3), with a modification in the grading of evidence (4). Although the rating system we chose differs from those used in previous ATA and AACE clinical practice guidelines, the approach conforms with the recently updated AACE protocol for standardized production of clinical practice guidelines (5). The balance between benefits and risks, quality of evidence, applicability, and certainty of the baseline risk are all considered in judgments about the strength of recommendations (6). Grading the quality of the evidence takes into account study design, study quality, consistency of results, and directness of the evidence. The strength of a recommendation is indicated by the number 1 or 2. Grade 1 indicates a strong recommendation (for or against) that applies to most patients in most circumstances with benefits of action clearly outweighing the risks and burdens (or vice versa). In contrast, Grade 2 indicates a weak recommendation or a suggestion that may not be appropriate for every patient, depending on context, patient values, and preferences. The risks and benefits or burdens associated with a weak recommendation are closely balanced or uncertain and the statement is generally associated with the phrase ”we suggest” or ”should be considered.” The quality of the evidence is indicated by plus signs, such that + denotes low quality evidence; ++, moderate quality evidence; and +++, high quality evidence, based on consistency of results between studies and study design, limitations, and the directness of the evidence. Table 1 describes the criteria to be met for each rating category. Each recommendation is preceded by a description of the evidence and, in some cases, followed by a remarks section including technical suggestions on issues such as dosing and monitoring.

Presentation and endorsement of recommendations

The organization of the task force’s recommendations is presented in Table 2. The page numbers and the location key can be used to locate specific topics and recommendations. Specific recommendations are presented within boxes in the main body of the text. Location keys can be copied into the Find or Search function in a file or Web page to rapidly navigate to a particular section. A listing of the recommendations without text is provided as Appendix A.

TABLE 2. ORGANIZATION OF THE TASK FORCE’S RECOMMENDATIONS

Location key

Description

Page

[A]

Background

597

[B]

How should clinically or incidentally discovered thyrotoxicosis be evaluated and initially managed?

597

 

[B1]     Assessment of disease severity

597

 

[B2]     Biochemical evaluation

598

 

[B3]     Determination of etiology

598

 

[B4]     Symptomatic management

599

[C]

How should overt hyperthyroidism due to GD be managed?

600

[D]

If 131I therapy is chosen as treatment for GD, how should it be accomplished?

601

 

[D1]     Preparation of patients with GD for 131I therapy

601

 

[D2]     Administration of 131I in the treatment of GD

601

 

[D3]     Patient follow-up after 131I therapy for GD

602

 

[D4]     Treatment of persistent Graves’ hyperthyroidism following radioactive iodine therapy

603

[E]

If antithyroid drugs are chosen as initial management of GD, how should the therapy be managed?

603

 

[E1]     Initiation of antithyroid drug therapy for the treatment of GD

603

 

[E2]     Monitoring of patients taking antithyroid drugs

604

 

[E3]     Management of allergic reactions

604

 

[E4]     Duration of antithyroid drug therapy for GD

604

[F]

If thyroidectomy is chosen for treatment of GD, how should it be accomplished?

605

 

[F1]      Preparation of patients with GD for thyroidectomy

605

 

[F2]      The surgical procedure and choice of surgeon

605

 

[F3]      Postoperative care

605

[G]

How should thyroid nodules be managed in patients with GD?

606

[H]

How should thyroid storm be managed?

606

[I]

How should overt hyperthyroidism due to TMNG or TA be treated?

607

[J]

If 131I therapy is chosen as treatment for TMNG or TA, how should it be accomplished?

609

 

[J1]      Preparation of patients with TMNG or TA for 131I therapy

609

 

[J2]      Evaluation of thyroid nodules prior to radioioactive iodine therapy

609

 

[J3]      Administration of radioactive iodine in the treatment of TMNG or TA

609

 

[J4]      Patient follow-up after 131I therapy for TMNG or TA

610

 

[J5]      Treatment of persistent or recurrent hyperthyroidism following 131I therapy for TMNG or TA

610

[K]

If surgery is chosen, as treatment for TMNG or TA, how should it be accomplished?

610

 

[K1]     Preparation of patients with TMNG or TA for surgery

610

 

[K2]     The surgical procedure and choice of surgeon

610

 

[K3]     Postoperative care

611

 

[K4]     Treatment of persistent or recurrent disease following surgery for TMNG or TA

611

[L]

Is there a role for antithyroid drug therapy in patients with TMNG or TA?

611

[M]

Is there a role for radiofrequency, thermal or alcohol ablation in the management of TA or TMNG?

612

[N]

How should GD be managed in children and adolescents?

612

 

[N1]     General approach

612

[O]

If antithyroid drugs are chosen as initial management of GD in children, how should the therapy be managed?

612

 

[O1]     Initiation of antithyroid drug therapy for the treatment of GD in children

612

 

[O2]     Symptomatic management of Graves’ hyperthyroidism in children

613

 

[O3]     Monitoring of children taking methimazole

613

 

[O4]     Monitoring of children taking propylthiouracil

614

 

[O5]     Management of allergic reactions in children taking methimazole

614

 

[O6]     Duration of methimazole therapy in children with GD

614

[P]

If radioactive iodine is chosen as treatment for GD in children, how should it be accomplished?

615

 

[P1]      Preparation of pediatric patients with GD for 131I therapy

615

 

[P2]      Administration of 131I in the treatment of GD in children

615

 

[P3]      Side-effects of 131I therapy in children

615

[Q]

If thyroidectomy is chosen as treatment for GD in children, how should it be accomplished?

616

 

[Q1]     Preparation of children with GD for thyroidectomy

616

[R]

How should SH be managed?

617

 

[R1]     Frequency and causes of subclinical hyperthyroidism

617

 

[R2]     Clinical significance of subclinical hyperthyroidism

617

 

[R3]     When to treat subclinical hyperthyroidism

617

 

[R4]     How to treat subclinical hyperthyroidism

618

 

[R5]     End points to be assessed to determine effective therapy of subclinical hyperthyroidism

618

[S]

How should hyperthyroidism in pregnancy be managed?

619

 

[S1]      Diagnosis of hyperthyroidism in pregnancy

619

 

[S2]      Management of hyperthyroidism in pregnancy

619

 

[S3]      The role of TRAb levels measurement in pregnancy

621

 

[S4]      Postpartum thyroiditis

621

[T]

How should hyperthyroidism be managed in patients with Graves’ ophthalmopathy?

622

 

[T1]     Assessment of disease activity and severity

623

 

[T2]     Prevention of GO

624

 

[T3]     Treatment of hyperthyroidism in patients with active GO of mild severity

625

 

[T4]     Treatment of hyperthyroidism in patients with active and moderate-to-severe or sight-threatening GO

625

 

[T5]     Treatment of GD in patients with inactive GO

625

[U]

How should overt drug-induced thyrotoxicosis be managed?

626

 

[U1]     Iodine-induced thyrotoxicosis

626

 

[U2]     Cytokine-induced thyrotoxicosis

627

 

[U3]     Amiodarone-induced thyrotoxicosis

627

[V]

How should thyrotoxicosis due to destructive thyroiditis be managed?

628

 

[V1]     Subacute thyroiditis

628

 

[V2]     Painless thyroiditis

628

 

[V3]     Acute thyroiditis

628

[W]

How should thyrotoxicosis due to unusual causes be managed?

629

 

[W1]    TSH-secreting pituitary tumors

629

 

[W2]    Struma ovarii

629

 

[W3]    Choriocarcinoma

629

 

[W4]    Thyrotoxicosis factitia

630

 

[W5]    Functional thyroid cancer metastases

630

GD, Graves’ disease; GO, Graves’ ophthalmopathy; SH, subclinical hyperthyroidism; TA, toxic adenoma; TMNG, toxic multinodular goiter; TRAb, thyrotropin receptor antibody; TSH, thyroid-stimulating hormone.

The final document was approved by the ATA and AACE on March 15, 2011 and officially endorsed (in alphabetical order) by American Academy of Otolaryngology– Head and Neck Surgery, Associazione Medici Endocrinologi, British Association of Endocrine and Thyroid Surgeons, Canadian Paediatric Endocrine Group–Groupe Canadien d’Endocrinologie Pe´diatrique (endorsement of pediatric section only), European Association of Nuclear Medicine, The Endocrine Society, European Society of Endocrinology, European Society of Endocrine Surgeons, European Thyroid Association, International Association of Endocrine Surgeons, Latin American Thyroid Society, Pediatric Endocrine Society, Italian Endocrine Society, and Society of Nuclear Medicine.