Results of health technology assessments of orphan drugs in Germany-lack of added benefit, evidence gaps, and persisting unmet medical needs.

Background: The number of orphan drug (OD) approvals has increased sharply in Europe. In Germany, all ODs are initially subject to a limited assessment after market access. Their added benefit over the standard of care is accepted as established upon EU approval; a regular health technology assessment (HTA) is performed only in certain cases.

A systematic comparison of different composite measures (DAS 28, CDAI, SDAI, and Boolean approach) for determining treatment effects on low disease activity and remission in rheumatoid arthritis.

Background: Some composite measures for determining the treatment effects of disease-modifying antirheumatic drugs on remission and low disease activity (LDA) in rheumatoid arthritis (RA) may produce misleading results if they include an acute phase reactant (APR). To inform the choice of appropriate measure, we performed a systematic comparison of treatment effects using different composite measures.

Methods: We used data generated for a systematic review of biologics in RA conducted by the Institute for Quality and Efficiency in Health Care and data from systematic reviews of newer biologics and Janus kinase (JAK) inhibitors provided by sponsors.

Results on patient-reported outcomes are underreported in summaries of product characteristics for new drugs.

Background: Summaries of product characteristics (SmPCs) are regulatory documents published upon drug approval. They should report all relevant study data and advise how to use drugs safely and effectively. Patient-reported outcomes (PROs) are increasingly used in clinical trials to incorporate the patient perspective-SmPCs should thus adequately report PROs.

Guideline appraisal with AGREE II: online survey of the potential influence of AGREE II items on overall assessment of guideline quality and recommendation for use.

Background: The AGREE II instrument is the most commonly used guideline appraisal tool. It includes 23 appraisal criteria (items) organized within six domains. AGREE II also includes two overall assessments (overall guideline quality, recommendation for use).

Information on new drugs at market entry: retrospective analysis of health technology assessment reports versus regulatory reports, journal publications, and registry reports.

Background: When a new drug becomes available, patients and doctors require information on its benefits and harms. In 2011, Germany introduced the early benefit assessment of new drugs through the act on the reform of the market for medicinal products (AMNOG). At market entry, the pharmaceutical company responsible must submit a standardised dossier containing all available evidence of the drug's added benefit over an appropriate comparator treatment.

[Patient-relevant outcomes and surrogates in the early benefit assessment of drugs: first experiences].

The Act on the Reform of the Market for Medicinal Products (AMNOG) became effective in Germany on January 1, 2011. Since then, the assessment of the added benefit of new drugs versus a therapeutic standard on the basis of dossiers submitted by pharmaceutical companies has been required by law. The Federal Joint Committee (G-BA) generally commissions the Institute for Quality and Efficiency in Health Care (IQWiG) with this task.

Impact of inclusion of industry trial results registries as an information source for systematic reviews.

Background: Clinical trial results registries may contain relevant unpublished information. Our main aim was to investigate the potential impact of the inclusion of reports from industry results registries on systematic reviews (SRs).

Methods: We identified a sample of 150 eligible SRs in PubMed via backward selection.

Early benefit assessment of new drugs in Germany - results from 2011 to 2012.

Rising drug costs in Germany led to the Act on the Reform of the Market for Medicinal Products (AMNOG) in January 2011. For new drugs, pharmaceutical companies have to submit dossiers containing all available evidence to demonstrate an added benefit versus an appropriate comparator therapy. The Federal Joint Committee (G-BA), the main decision-making body of the statutory healthcare system, is responsible for the overall procedure of "early benefit assessment".

Completeness of reporting of patient-relevant clinical trial outcomes: comparison of unpublished clinical study reports with publicly available data.

Background: Access to unpublished clinical study reports (CSRs) is currently being discussed as a means to allow unbiased evaluation of clinical research. The Institute for Quality and Efficiency in Health Care (IQWiG) routinely requests CSRs from manufacturers for its drug assessments. Our objective was to determine the information gain from CSRs compared to publicly available sources (journal publications and registry reports) for patient-relevant outcomes included in IQWiG health technology assessments (HTAs) of drugs.

Access to regulatory data from the European Medicines Agency: the times they are a-changing.

Systematic reviewers are increasingly trying to obtain regulatory clinical study reports (CSRs) to correct for publication bias. For instance, our organization, the Institute for Quality and Efficiency in Health Care, routinely asks drug manufacturers to provide full CSRs of studies considered in health technology assessments. However, since cooperation is voluntary, CSRs are available only for a subset of studies analysed.

Impact of document type on reporting quality of clinical drug trials: a comparison of registry reports, clinical study reports, and journal publications.

Objective: To investigate to what extent three types of documents for reporting clinical trials provide sufficient information for trial evaluation.

Design: Retrospective analysis

Data Sources: Primary studies and corresponding documents (registry reports, clinical study reports, journal publications) from 16 health technology assessments of drugs conducted by the German Institute for Quality and Efficiency in Health Care between 2006 and February 2011. Data analysis We assessed reporting quality for each study and each available document for six items on methods and six on outcomes, and dichotomised them as "completely reported" or "incompletely reported.

Reporting bias in medical research - a narrative review.

Reporting bias represents a major problem in the assessment of health care interventions. Several prominent cases have been described in the literature, for example, in the reporting of trials of antidepressants, Class I anti-arrhythmic drugs, and selective COX-2 inhibitors. The aim of this narrative review is to gain an overview of reporting bias in the medical literature, focussing on publication bias and selective outcome reporting.

Disagreement in primary study selection between systematic reviews on negative pressure wound therapy.

Background: Primary study selection between systematic reviews is inconsistent, and reviews on the same topic may reach different conclusions. Our main objective was to compare systematic reviews on negative pressure wound therapy (NPWT) regarding their agreement in primary study selection.

Methods: This retrospective analysis was conducted within the framework of a systematic review (a full review and a subsequent rapid report) on NPWT prepared by the Institute for Quality and Efficiency in Health Care (IQWiG).