Assessment of prostate-specific antigen screening: an evidence-based report by the German Institute for Quality and Efficiency in Health Care.

CONTEXT: Prostate-specific antigen (PSA) testing increases prostate cancer diagnoses and reduces long-term disease-specific mortality, but also results in overdiagnoses and treatment-related harms. OBJECTIVE: To systematically assess the benefits and harms of population-based PSA screening and the potential net benefit to inform health policy decision-makers in Germany. EVIDENCE ACQUISITION: We performed a protocol-guided comprehensive literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. All steps were performed by one or two investigators; any discrepancies were resolved by consensus. To allow subgroup analyses for identifying the optimal screening parameters, the eight national trials conducted under the umbrella of the European Randomised study of Screening for Prostate Cancer (ERSPC) were included as individual trials. EVIDENCE SYNTHESIS: We included a total 11 randomised controlled trials (RCTs) with a total of 416 000 study participants. For all-cause mortality, we found neither benefit nor harm. PSA screening was associated with a reduced risk of both prostate cancer mortality and the development of metastases. For the outcomes of health-related quality of life, adverse effects and the consequences of false-negative screening results there was no difference; however, this was due to the lack of eligible RCT data. Finally, PSA screening was associated with large numbers of overdiagnoses with adverse downstream consequences of unnecessary treatment (e.g. incontinence, erectile dysfunction) and large numbers of false-positive PSA tests leading to biopsies associated with a small but not negligible risk of complications. Limitations of this assessment include the clinical heterogeneity and methodological limitations of the underlying studies. CONCLUSIONS: The benefits of PSA-based prostate cancer screening do not outweigh its harms. We failed to identify eligible screening studies of newer biomarkers, PSA derivatives or modern imaging modalities, which may alter the balance of benefit to harm. PATIENT SUMMARY: In the present study, we reviewed the evidence on the PSA blood test to screen men without symptoms for prostate cancer. We found that the small benefits experienced by some men do not outweigh the harms to many more men.

[Development of Decision Aids for Organized Cervical Carcinoma Screening in Germany]. / Entwicklung von Entscheidungshilfen für das organisierte Zervixkarzinom-Screening in Deutschland.

AIM OF THE STUDY: The Federal Joint Committee has decided to introduce organized cervical carcinoma screening in 2020. The present work describes the development of decision aids that will be sent to women in this program. METHODS: A systematic search for qualitative studies and surveys was conducted to gather information on experiences, attitudes and information needs. Furthermore, we searched for systematic reviews on advantages and disadvantages of screening. An existing decision analysis for cervical carcinoma screening in Germany was used. The designs were subjected to a qualitative test (focus groups with 26 women and 8 expert interviews), to a quantitative user test (online survey n=2,014 women) and to a public hearing. RESULTS: Most women found the decision aids informative and helpful. The majority would recommend the use of these materials to others. For many women, part of the information was new, although they had been involved in cervical cancer screening for some time. The presentation of the advantages and disadvantages was judged to be balanced. However, 10% changed their attitude towards participation and 70% of women would attend screening. CONCLUSION: The decision aids found a high acceptance among the users. They can help to reduce knowledge deficits on cervical carcinoma screening and support a informed decision making.

Screening for sickle cell disease in newborns: a systematic review.

BACKGROUND: Sickle cell disease (SCD) is an inherited autosomal recessive disorder caused by the replacement of normal haemoglobin (HbA) by mutant Hb (sickle Hb, HbS). The sickle-shaped red blood cells lead to haemolysis and vaso-occlusion. Especially in the first years of life, patients with SCD are at high risk of life-threatening complications. SCD prevalence shows large regional variations; the disease predominantly occurs in sub-Saharan Africa. We aimed to systematically assess the evidence on the benefit of newborn screening for SCD followed by an earlier treatment start. METHODS: We systematically searched bibliographic databases (MEDLINE, EMBASE, Cochrane Databases, and the Health Technology Assessment Database), trial registries, and other sources to identify systematic reviews and randomised controlled trials (RCTs) or non-randomised trials on newborn screening for SCD. The last search was in 07/2020. Two reviewers independently reviewed abstracts and full-text articles and assessed the risk of bias of the studies included. Data were extracted by one person and checked by another. As meta-analyses were not possible, a qualitative summary of results was performed. RESULTS: We identified 1 eligible study with direct evidence: a Jamaican retrospective study evaluating newborn screening for SCD followed by preventive measures (prevention of infections and education of parents). The study included 500 patients with SCD (intervention group, 395; historical control group, 105). Although the results showed a high risk of bias, the difference between the intervention and the control group was very large: mortality in children decreased by a factor of about 10 in the first 5 years of life (0.02% in the intervention group vs. 0.19% in the control group, odds ratio 0.09; 95% confidence interval [0.04; 0.22], p < 0.001). CONCLUSION: The results are based on a single retrospective study including historical controls. However, the decrease of mortality by a factor of 10 is unlikely to be explained by bias alone. Therefore, in terms of mortality, data from this single retrospective study included in our systematic review suggest a benefit of newborn screening for SCD (followed by preventive measures) versus no newborn screening for SCD (weak certainty of conclusions).

Systematic review of current guideline appraisals performed with the Appraisal of Guidelines for Research & Evaluation II instrument-a third of AGREE II users apply a cut-off for guideline quality.

OBJECTIVES: To investigate whether Appraisal of Guidelines for Research & Evaluation (AGREE) II users apply a cut-off based on standardized domain scores or overall guideline quality to distinguish between high- and low-quality guidelines, as well as to investigate which criteria they use to generate this cut-off and which type of cut-off they apply. STUDY DESIGN AND SETTING: We conducted a systematic search in MEDLINE, EMBASE, DARE, and the HTA-database for German- and English-language studies appraising guidelines with AGREE II. Information on cut-offs was extracted and analyzed descriptively. RESULTS: We identified 118 relevant publications. Thirty-nine (33%) used a cut-off, of which 24 (62%) used a 2-step and 13 (33%) used a 3-step approach. The cut-off for high quality lay between 50% and 70% (2-step) and 60% and 83% (3-step) of the highest possible rating. Twenty-four (62%) publications applied a cut-off based on standardized domain scores and 7 (18%) based on overall guideline quality. Eleven (28%) applied cut-offs to derive the recommendation for guideline use. CONCLUSION: A third of AGREE II users apply a cut-off to distinguish between high- and low-quality guidelines, often without clearly describing how the cut-off is generated. Many users might welcome a clear distinction between high- and low-quality guidelines; specifying a cut-off for this purpose might be useful.

Guideline appraisal with AGREE II: Systematic review of the current evidence on how users handle the 2 overall assessments.

INTRODUCTION: The Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument is the most commonly used guideline appraisal tool. It includes 23 appraisal criteria (items) organized within 6 domains and 2 overall assessments (1. overall guideline quality; 2. recommendation for use). The aim of this systematic review was twofold. Firstly, to investigate how often AGREE II users conduct the 2 overall assessments. Secondly, to investigate the influence of the 6 domain scores on each of the 2 overall assessments. MATERIALS AND METHODS: A systematic bibliographic search was conducted for publications reporting guideline appraisals with AGREE II. The impact of the 6 domain scores on the overall assessment of guideline quality was examined using a multiple linear regression model. Their impact on the recommendation for use (possible answers: "yes", "yes, with modifications", "no") was examined using a multinomial regression model. RESULTS: 118 relevant publications including 1453 guidelines were identified. 77.1% of the publications reported results for at least one overall assessment, but only 32.2% reported results for both overall assessments. The results of the regression analyses showed a statistically significant influence of all domains on overall guideline quality, with Domain 3 (rigour of development) having the strongest influence. For the recommendation for use, the results showed a significant influence of Domains 3 to 5 ("yes" vs. "no") and Domains 3 and 5 ("yes, with modifications" vs. "no"). CONCLUSIONS: The 2 overall assessments of AGREE II are underreported by guideline assessors. Domains 3 and 5 have the strongest influence on the results of the 2 overall assessments, while the other domains have a varying influence. Within a normative approach, our findings could be used as guidance for weighting individual domains in AGREE II to make the overall assessments more objective. Alternatively, a stronger content analysis of the individual domains could clarify their importance in terms of guideline quality. Moreover, AGREE II should require users to transparently present how they conducted the assessments.

Prospective comparison of search strategies for systematic reviews: an objective approach yielded higher sensitivity than a conceptual one.

BACKGROUND: In the development of search strategies for systematic reviews, "conceptual approaches" are generally recommended to identify appropriate search terms for those parts of the strategies for which no validated search filters exist. However, "objective approaches" based on search terms identified by text analysis are increasingly being applied. OBJECTIVES: To prospectively compare an objective with a conceptual approach for the development of search strategies. METHODS: Two different MEDLINE search strategies were developed in parallel for five systematic reviews covering a range of topics and study designs. The Institute for Quality and Efficiency in Health Care (IQWiG) applied an objective approach, and external experts applied a conceptual approach for the same research questions. For each systematic review, the citations retrieved were combined and the overall pool of citations screened to determine sensitivity and precision. RESULTS: The objective approach yielded a weighted mean sensitivity and precision of 97% and 5%. The corresponding values for the conceptual approach were 75% and 4%. CONCLUSION: Our findings indicate that the objective approach applied by IQWiG for search strategy development yields higher sensitivity than and similar precision to a conceptual approach. The main advantage of the objective approach is that it produces consistent results across searches.

Development of search strategies for systematic reviews: validation showed the noninferiority of the objective approach.

BACKGROUND: Different approaches can be adopted for the development of search strategies of systematic reviews. The objective approach draws on already established text analysis methods for developing search filters. Our aim was to determine whether the objective approach for the development of search strategies was noninferior to the conceptual approach commonly used in Cochrane reviews (CRs). METHODS: We conducted a search for CRs published in the Cochrane Library. The studies included in the CRs were searched for in MEDLINE and represented the total set. We then tested whether references previously removed could be identified via the objective approach. We also reconstructed the original search strategies from the CRs to determine why references could not be identified by the objective approach. As we performed the validation of the search strategies without study filters, we used only sensitivity as a quality measure and did not calculate precision. RESULTS: The objective approach yielded a mean sensitivity of 96% based on 13 searches. The noninferiority test showed that this approach was noninferior to the conceptual approach used in the CRs (P < 0.002). An additional descriptive analysis showed that the original MEDLINE strategies could identify only 86% of all references; however, this lower sensitivity was largely due to one CR. CONCLUSION: To the best of our knowledge, our findings indicate for the first time that the objective approach for the development of search strategies is noninferior to the conceptual approach.