Background: Amblyopia and amblyogenic factors like strabismus and refractive errors are the most common vision disorders in children. Although different studies suggest that preschool vision screening is associated with a reduced prevalence rate of amblyopia, the value of these programmes is the subject of a continuing scientific and health policy discussion. Therefore, this systematic review focuses on the question of whether screening for amblyopia in children up to the age of six years leads to better vision outcomes.

Diagnostic test accuracy of preschool vision screening tests can only be sufficiently investigated after establishing age-related values defining amblyopia, refractive errors and binocular disorders. To address these questions, we recommend a controlled longitudinal study design.

Uncertainties remain about the age at which treatment for amblyopia or its risk factors is most effective. Beside methodological limitations, the design of the studies made it challenging to address this question sufficiently.

Randomized controlled trials (RCTs) add important information to diagnostic accuracy studies in the evaluation of PET and PET/CT. We evaluated how many RCTs on PET existed, which clinical topics they addressed, and what their design and quality were. Methods: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (Clinical Trials) up to August 2010. We also searched in ClinicalTrials.gov and the International Clinical Trials Registry Platform for ongoing RCTs up to March 2011. Titles and abstracts and full texts were screened independently by 2 reviewers. Study characteristics were extracted with standard extraction sheets for ongoing and published RCTs, and risk of bias was assessed for published ones. Results: We identified 54 RCTs, 12 of which were published. The main topics in published studies were non-small cell lung cancer and colorectal cancer; only 3 were conducted in nononcologic fields (this trend was similar in ongoing studies, in which the most common topic was Hodgkin disease). The main indications in the oncologic PET studies were staging in published studies and restaging (mostly including an early assessment of treatment response) in ongoing ones. All except 1 of the published studies applied a marker-based strategy design, whereas about 43% (18/42) of ongoing studies use a more efficient design (Enrichment Design or Marker by Treatment Interaction Design). Conclusion: A relatively high number of ongoing RCTs of PET in several oncologic fields are expected to produce robust results over the next few years. For nononcologic topics, further high-quality studies are still needed to ascertain the benefit of this technique for patients. As funding is usually difficult in nondrug topics, alternative concepts of funding, which should also involve the manufacturers of diagnostic devices, but also more efficient study designs, should be applied to bridge the evidence gap on PET in the near future.Key Words: positron-emission tomography; randomized controlled trials; evidence-based medicine; systematic review Posi tron emission tomography (PET) or PET/CT is a rapidly evolving technique that enables the imaging of metabolically active tissue, such as many types of cancer (1). PET is widely applied because of its expected capacity to detect, describe, and monitor various malignant and benign diseases. Between 2004 and 2008, the annual rates of PET examinations increased by 18% in the United States (2). In most European countries, the annual rate of PET examinations is increasing at a similar pace and ranges between 1,000 and 2,000 per 1 million inhabitants (3).According to the principles of evidence-based medicine, evidence from RCTs measuring patient-relevant outcomes (i.e., mortality, morbidity, and quality of life) is required for new diagnostic tests or markers (e.g., for those with higher sensitivity than existing ones) to draw valid conclusions as to their benefit (4-6). Studies investigating diagnostic test accuracy alone are unable to prove that patients with the disease...

The call by the Institute for Quality and Efficiency in Health Care (IQWiG) for randomised controlled trials (RCTs) to prove the patient-relevant benefit of positron emission tomography (PET) is currently a controversial topic in Germany. From a methodological point of view there is essentially no difference between diagnostic procedures and therapeutic (drug or non-drug) interventions in proving their causal benefit. A broad consensus has been reached since the 1960s (e.g. FDA regulations) that RCTs are the methodological gold standard for therapeutic interventions. Nevertheless, the same arguments that were cited against RCTs in assessing the benefit of therapeutic interventions are now used against RCTs in evaluating diagnostic tests (e.g. ethical problems, feasibility, etc.). This paper summarizes the central methodological arguments of the discussion on the benefit assessment of PET in malignant lymphomas from the perspective of IQWiG and its external experts.