Table 1

Characteristics of the studies

Guidelines	Funding body	Country	Population	Target users	Writers	Evidence base	Evidence level	Grading	Guideline review	Update
ARA 2010 1	Professional society	Australia	Biological therapy	Rheumatologists	Rheumatologists	Guidelines	NS	NS	NS	NS
Aguado et al 20093	Industry, Professional society	Spain	Organ transplant	Transplant physicians	Transplant infectious disease specialists	Literature, consensus, experts	I-III*	A-E †	NS	NS
CDC 20169	Office of AIDS Research,	USA	HIV	Clinicians	Multidisciplinary	Literature, experts	I-III‡	A-C§	Expert review, public consultation	6 months
WHO 201510	Ministry of health Italy, WHO,	WHO	All	Tuberculosis physicians	Multidisciplinary	Literature, experts	GRADE¶	Strong/conditional**	Expert review, peer review	2020
Beglinger et al 200715	NS	Switzerland	Anti TNF-alpha therapy	Clinicians	Multidisciplinary	Literature, experts	NS	NS	NS	NS
Cantini et al 201516	NS	Italy	Biological therapy	Clinicians	Multidisciplinary	Literature, experts	NS	NS	NS	NS
Doherty et al 200817	Professional body	USA	Patients with psoriasis	NS	Dermatologists	Literature, experts	I-IV (Shekelle et al)††	NS	Medical Board	NS
Duarte et al 201218	NS	Portugal	Biological therapy	Clinicians	Multidisciplinary	Guidelines, experts	A-D‡‡	NS	NS	NS
Fonseca et al 200819	NS	Portugal	Biological therapy	Rheumatologists	Multidisciplinary	Literature, guidelines	NS	NS	Expert, public consultation	NS
Hodkinson et al 201320	Professional body	South Africa	Patients with rheumatoid arthritis	Clinicians	Rheumatologists	Literature, guideline, expert, stakeholder	NS	NS	Public/stakeholder consultation	2 years
Kavanagh et al 200821	Professional body	Ireland	Anti TNF-alpha therapy	Clinicians	Multidisciplinary	Literature, guidelines, experts	NS	NS	NS	NS
Keith et al 201422	Nil	USA	Immunosuppression	Dermatologists	Multidisciplinary	Literature, guidelines	NS	NS	NS	NS
Koike et al 200723	Professional body, Government	Japan	Anti-TNF alpha therapy	Rheumatologists	NS	Experts	NS	NS	NS	NS
Lichauco et al 200624	NS	Philippines	Biological therapy	Physicians	Multidisciplinary	Literature, guidelines	Level 1-4§§	PHEX guidelines¶¶	Expert peer review, public consultation	NS
Salmon 200225	Not specified	France	Rheumatoid arthritis	Rheumatologists	Multidisciplinary	NS	NS	NS	NS	NS
Mir Viladrich et al 201626	NS	Spain	Biological therapy	Clinicians	Multidisciplinary	Guidelines, experts	NS	A-C, I-III***	NS	NS
Mok et al 201127	NS	Hong Kong	Rheumatoid arthritis	Rheumatologists	Rheumatologists	Guidelines	A-D†††	NS	NS	As required
Nordgaard-Lassen et al 201228	NS	Denmark	Biological therapy	Clinicians	Gastroenterologists	Literature	I-IV‡‡‡	A-C§§§	NS	NS
BTS 200529	NS	UK	Anti TNF-alpha therapy	Physician	Multidisciplinary	Literature, experts	SIGN¶¶¶	SIGN****	Professional membership consultation, peer review	2008
Smith et al 201730	British Association of Dermatologists	UK	Psoriasis	Dermatologists	Multidisciplinary	Literature	GRADE¶	GRADE: Strong/weak/no††††	Professional membership consultation, peer review	As required
Solovic et al 201031	NS	Europe	Biological therapy	Clinicians	Multidisciplinary	Literature	NS	A-D‡‡‡‡	NS	NS
Carrascosa et al 201632	Gebro Pharma	Spain	Methotrexate therapy	Dermatologists	Dermatologists	Literature, guidelines	SIGN¶¶¶	SIGN****	NS	NS
Bumbacea et al 201233	Professional society	Europe	All transplant	Transplant physicians	Transplant infectious disease specialists	Literature, guidelines	NS	A-D‡‡‡‡	NS	NS
KDIGO 200934	KDIGO, multiple sponsors	International	Kidney transplant recipients	Clinicians	Multidisciplinary	Literature, experts	A-D§§§§	Level 1–2, not graded¶¶¶¶	NS	NS
Meije et al 201435	NS	Spain	Solid organ transplant	Transplant physicians	Multidisciplinary	Literature	Level A-D, I-IV‡‡	NS	NS	NS
EBPG 200236	NS	Europe	Renal transplant	Transplant physicians	NS	NS	A-D*****	NS	NS	NS
Subramanian and Morris 201337	American Society of Transplantation	USA	Solid organ transplant recipients	Transplant physicians	Transplant infectious disease physicians	Literature, experts	I-III‡‡	NS	NS	NS
Tomblyn et al 200938	Member societies	International/ USA/Canada	Stem cell transplant recipients	Clinicians	Multidisciplinary	Literature, experts	I-III†††††	A-E§§§§§	NS	NS
Pozniak et al 201139	Nil	UK	HIV	Physicians	HIV physicians	Literature, guidelines	I-III‡‡‡‡‡	A-E¶¶¶¶¶	NS	NS
SA 201040	NS	South Africa	HIV	HIV treatment providers	NS	NS	NS	NS	NS	NS
Santin et al 201641	SEPAR, SEIMC	Spain	All	Clinicians	Multidisciplinary	Literature	GRADE¶	GRADE: weak/strong	NS	5 years
Al Jahdali et al 201042	Professional society	Saudi Arabia	All susceptible patients	Clinicians	Multidisciplinary	Experts	NS	NS	NS	NS
ECDC 201143	ECDC	Europe	Immunocompromised	National bodies	Multidisciplinary	Literature, experts	NS	NS	NS	NS
Mazurek et al 201044	CDC	USA	All	Public health officials, physicians, others	Multidisciplinary	Literature, experts	NS	NS	NS	NS
Taylor et al 200545	Professional bodies	USA	All	Healthcare workers	Multidisciplinary	Literature, experts	I-III******	A-C††††††	NS	NS
CTC 200846	Public Health Agency	Canada	Immunocompromised patients	NS	Multidisciplinary	Literature, experts	NS	NS	NS	Periodic
Japanese Society for Tuberculosis 201447	NS	Japan	All susceptible populations	Clinicians	NS	NS	NS	NS	NS	NS
NICE 201648	NCCCC	UK	All susceptible populations	All healthcare workers and public	Multidisciplinary	Literature review	GRADE¶	Offer/do not offer/consider‡‡‡‡‡‡	Stakeholders, peer review	As required
I: Evidence from at least 1 well-designed and performed trial, II: Evidence from at least one well designed non-RCT, cohort or case control or non-controlled experimental study with non-conclusive results, III: Expert opinion based on clinical experience, descriptive studies, report from expert panel. †A: Solid evidence of clinical benefit, B: Solid or moderately solid evidence for efficacy, but clinical benefit is limited, C: Insufficient evidence for efficacy, D: Moderately solid evidence for lack of efficacy, E: Strong evidence for lack of efficacy. ‡I: One or more RCT with clinical outcomes and/or validated laboratory endpoints, II: One or more well-designed, non-randomised trials or observational cohort studies with long-term clinical outcomes III: Expert opinion. §A: Strong recommendation for the statement, B: Moderate recommendation for the statement, C: Optional recommendation for the statement. ¶GRADE—High: Further research is very unlikely to change our confidence in the estimate of effect. Moderate; Further research is likely to have an important impact on our confidence in the effect. Low: Further research is very likely to have an impact on the estimate of effect and is likely to change the estimate. Very low: Any estimate of effect is very uncertain. *(1) A strong recommendation is one for which the Panel was confident that the desirable effects of adherence to the recommendation outweigh the undesirable effects. This could be either in favour of or against an intervention. (2) A conditional recommendation is one for which the Panel concluded that the desirable effects of adherence to the recommendation probably outweigh the undesirable effects, but the Panel was not confident about these trade-offs. Reasons for not being confident included: absence of high-quality evidence (data to support the recommendation are scant); presence of imprecise estimates of benefits or harms (new evidence may result in changing the balance of risk to benefit); uncertainty or variation regarding how different individuals value the outcomes (only applicable to a specific group, population or setting); small benefits and benefits that may not be worth the costs (including the costs of implementing the recommendation).

††IA: Evidence includes evidence from meta-analysis of randomised controlled trials; IB: Evidence includes evidence from at least one randomised controlled trial; IIA: Evidence includes evidence from at least one controlled study without randomisation; IIB: Evidence includes evidence from at least one other type of quasi-experimental study; III: Evidence includes evidence from non-experimental descriptive studies, such as comparative studies, correlation studies and case-control studies; IV: Evidence includes evidence from expert committee reports or opinions or clinical experience of respected authorities or both.
‡‡Evidence level definitions not specified.
§§Level 1: An RCT that demonstrates a statistically signiﬁcant difference in at lest one major outcome or if the difference is not statistically signiﬁcant, an RCT of adequate sample size to exclude 25% difference in relative risk with 80% power, given the observed results. Level 2: An RCT that does not meet the Level 1 criteria. Level 3: A non-randomised trial with concurrent controls selected by some systematic method. Level 4: Before-after study or case series (at least 10 patients) with historical controls or controls drawn from other studies. Level 5: Case series (at least 10 patients) without controls. Experts’ opinion and clinical experience are included.
¶¶Level 1: Evaluation of evidence satisfies all of the following criteria: (1) effective treatment is documented in RCTs that observe effects on clinical outcomes; (2) the condition being screened has local prevalence data; (3) the screening test is validated and (4) the cost-effectiveness of the screening test, as well as treatment for the disease have been evaluated. Level 2: Evaluation of evidence satisﬁes #1 but not all of #2, #3 and #4. Level 3: Evaluation of evidence satisﬁes #2, #3 or #4 but not #1. Level 4: Evaluation of evidence satisﬁes none of the criteria.
***Recommendations according to categories of strength: (A) Good evidence to support the recommendation, (B) moderate evidence to support the recommendation, (C) poor evidence that does not enable the recommendation to be either supported or rejected. Recommendations according to the scientific quality. Grade I: Recommendation based on at least one well-designed, controlled, RCT. Grade II: Recommendation based on at least one well-designed, but not RCT, cohort studies, multiple time-series studies or very evident results in uncontrolled trials. Grade III: Recommendation based on the opinion of experts, descriptive studies or clinical experience.
††† Category A: At least one RCT or meta-analyses of RCTs or reviews if these contain category A references. Category B: At least one controlled trial without randomisation or at least one other type of experimental study or extrapolated recommendations from RCTs or meta-analyses. Category C: Non-experimental descriptive studies, such as comparative studies, correlational studies and case-control studies, which are extrapolated from RCTs, non-randomised controlled studies or other experimental studies. Category D: Expert committee reports or opinions or clinical experience of respected authorities. Also includes all abstracts.
‡‡‡I: Randomised, controlled clinical trials (therapeutic or diagnostic) and meta-analyses of randomised, controlled clinical trials or systematic reviews. II: Prospective and controlled but non-randomised investigations (cohort studies); diagnostic testing evaluated by direct methods. III: Studies that are controlled but not prospective (case-control studies); diagnostic testing evaluated by indirect methods. IV: Descriptive studies, expert opinions and narrative reviews.
§§§(A) randomised, controlled clinical trials (therapeutic or diagnostic) and meta-analyses of randomised, controlled clinical trials or systematic reviews. (B) Prospective and controlled but nonrandomised investigations (cohort studies); diagnostic testing evaluated by direct methods, OR Studies that are controlled but not prospective (case-control studies); diagnostic testing evaluated by indirect methods. (C) Descriptive studies, expert opinions and narrative reviews.
¶¶¶1++: High quality meta-analyses, systematic reviews of RCTs or RCTs with a very low risk of bias. 1+: Well conducted meta-analyses, systematic reviews of RCTs or RCTs with a low risk of bias. 12: Meta-analyses, systematic reviews of RCTs or RCTs with a high risk of bias. 2++: High-quality systematic reviews of case-control or cohort studies. High-quality case-control or cohort studies with a very low risk of confounding, bias or chance and a high probability that the relationship is causal. 2+: Well-conducted case-control or cohort studies with a low risk of confounding, bias or chance and a moderate probability that the relationship is causal. 22: Case-control or cohort studies with a high risk of confounding, bias or chance and a significant risk that the relationship is not causal. 3: Non-analytical studies (eg, case reports, case series). 4: Expert opinion.
****(A) At least one meta-analysis, systematic review, or RCT rated as 1++ and directly applicable to the target population or a systematic review of RCTs or a body of evidence consisting principally of studies rated as 1+ directly applicable to the target population and demonstrating overall consistency of results. (B) A body of evidence including studies rated as 2++ directly applicable to the target population and demonstrating overall consistency of results or extrapolated evidence from studies rated as 1++ or 1+. (C) A body of evidence including studies rated as 2+ directly applicable to the target population and demonstrating overall consistency of results or extrapolated evidence from studies rated as 2+. (D) Evidence level 3 or 4 or extrapolated evidence from studies rated as 2+.
††††Strong recommendation for use of an intervention: Benefits of the intervention outweigh the risks; most patients would choose the intervention while only a small proportion would not; for clinicians, most of their patients would receive the intervention; for policy makers, it would be a useful performance indicator. Weak recommendation for the use of an intervention: Risks and beneﬁts of the intervention are ﬁnely balanced; many patients would choose the intervention but many would not; clinicians would need to consider the pros and cons for the patient in the context of the evidence; for policy makers, it would be a poor performance indicator where variability in practice is expected. No recommendation: Insufﬁcient evidence to support any recommendation. Strong recommendation against the use of an intervention: Risks of the intervention outweigh the beneﬁts; most patients would not choose the intervention while only a small proportion would; for clinicians, most of their patients would not receive the interventions.
‡‡‡‡(A) Evidence is from end-points of well-designed RCTs that provide a consistent pattern of findings in the population for which the recommendation is made. Category A requires substantial numbers of studies involving substantial numbers of participants. (B) Evidence is from end-points of intervention studies that include only a limited number of patients, posthoc or subgroup analysis of RCTs or meta-analysis of RCTs. In general, category B pertains when few randomised trials exist, they are small in size, they were undertaken in a population that differs from the target population of the recommendation or the results are somewhat inconsistent. (C) Evidence is from outcomes of uncontrolled or non-randomised trials or from observational studies. (D) This category is used only in cases where the provision of some guidance was deemed valuable but the clinical literature addressing the subject was insufficient to justify placement in one of the other categories. The Panel consensus is based on clinical experience or knowledge that does not meet the criteria listed above.
§§§§(A) High, (B) moderate, (C) low, (D) very low.
¶¶¶¶Level 1: We recommend. Level 2: We suggest. No grade: Used, typically, to provide guidance based on common sense or where the topic does not allow adequate application of evidence.
*****(A) Guidelines are supported by at least one large published RCT or more. (B) Guidelines are supported by large open trials or smaller trials with consensus results. (C) Guidelines are derived from small or controversial studies or represent the opinion of the group of experts.
†††††I: Evidence from at least one well-executed randomised, controlled trial. II: Evidence from at least one well-designed clinical trial without randomisation; cohort or case-controlled analytic studies (preferably from more than one centre); multiple time-series studies or dramatic results from uncontrolled experiments. III: Evidence from opinions of respected authorities based on clinical experience, descriptive studies or reports of expert committees.
§§§§§(A) Both strong evidence for efficacy and substantial clinical benefit support recommendation for use. Should always be offered. (B) Moderate evidence for efficacy—or strong evidence for efficacy, but only limited clinical benefit—supports recommendation for use. Should generally be offered. (C) Evidence for efficacy is insufficient to support a recommendation for or against use or evidence for efficacy might not outweigh adverse consequences (eg, drug toxicity, drug interactions) or cost of the chemoprophylaxis or alternative approaches. Optional. (D) Moderate evidence for lack of efficacy or for adverse outcome supports a recommendation against use. Should generally not be offered. (E) Good evidence for lack of efficacy or for adverse outcome supports a recommendation against use. Should never be offered.
‡‡‡‡‡(I) At least one properly randomised trial with clinical endpoints. (II) Clinical trials either not randomised or conducted in other populations. (III) Expert opinion.
¶¶¶¶¶(A) Preferred; should generally be offered. (B) Alternative; acceptable to offer. (C) Offer when preferred or alternative regimens cannot be given. (D) Should generally not be offered. (E) Should never be offered.
******I: Evidence from at least one RCT; II: Evidence from (1) at least one well-designed clinical trial, without randomisation, (2) cohort or case-controlled analytic studies, (3) multiple times series, (4) dramatic results from uncontrolled experiments III evidence from opinions of respected authorities on the basis of cumulative public health experience, descriptive studies or reports of expert committees.
††††††A highly recommended in all circumstances, II recommended; implementation might be dependent on resource availability, C might be considered under exceptional circumstances.
‡‡‡‡‡‡(A) Level 1++ and directly applicable to the target population or level 1+ and directly applicable to the target population AND consistency of results. Evidence from NICE technology appraisal. (B) Level 2++, directly applicable to the target population and demonstrating overall consistency of results or extrapolated evidence from 1++ or 1+. (C) Level 2+, directly applicable to the target population and demonstrating overall consistency of results or extrapolated evidence from 2++. (D) Level 3 or 4 or extrapolated from 2+ or formal consensus or extrapolated from level 2 clinical evidence supplemented with health economic modelling. D (GPP): A good practice point (GPP) is a recommendation based on the experience of the GDG.
ARA, Australian Rheumatological Association; BTS, British Thoracic Society; CDC, centre for disease control; CTC, Canadian Tuberculosis Committee; EBPG, European Best Practice Guideline Expert Group on Renal Transplantation; ECDC, European Centre for Disease Prevention and Control; GRADE, Grading of Recommendations Assessment, Development and Evaluation; KDIGO, Kidney Disease Improving Global Outcomes; NCCCC, The National Collaborating Centre for Chronic Conditions; NICE, National Institute for Health and Care Excellence; NS, not specified; PHEX, Philippine Guidelines on Periodic Health Examination; RCT, randomised control study; SA, South Africa; SEIMC, Spanish Society of Infectious Disease and Clinical Microbiology; SEPAR, Spanish Society of Respiratory Disease and Thoracic Surgery; SIGN, Scottish Intercollegiate Guidelines Network; TNF, tumour necrosis factor.