Paternal consent in prenatal research: ethical aspects.

The role of mothers in prenatal research has been discussed extensively. Significantly less work has been done on the father's role. In this article, focusing on ethical issues, we seek to redress this imbalance. Examining the father's position in research conducted on pregnant women, we ask whether or not paternal consent ought to be required in addition to that of the pregnant woman. Having distinguished between different concepts of father and mother, we proceed by giving an overview of the reasons for requiring consent of the woman who is carrying the child. We then examine which of these reasons apply to the biological father, and show that some of them are relevant to the father. The case, roughly speaking, revolves around privacy issues, the father's future legal responsibilities, and the likelihood that he will care about the health and wellbeing of his future child. These factors in the decision problem should all be recognized, as should the fact that they can in principle be trumped by other considerations.

An exploratory open-label multicentre phase I/II trial evaluating the safety and efficacy of postnatal or prenatal and postnatal administration of allogeneic expanded fetal mesenchymal stem cells for the treatment of severe osteogenesis imperfecta in infants and fetuses: the BOOSTB4 trial protocol.

INTRODUCTION: Severe osteogenesis imperfecta (OI) is a debilitating disease with no cure or sufficiently effective treatment. Mesenchymal stem cells (MSCs) have good safety profile, show promising effects and can form bone. The Boost Brittle Bones Before Birth (BOOSTB4) trial evaluates administration of allogeneic expanded human first trimester fetal liver MSCs (BOOST cells) for OI type 3 or severe type 4. METHODS AND ANALYSIS: BOOSTB4 is an exploratory, open-label, multiple dose, phase I/II clinical trial evaluating safety and efficacy of postnatal (n=15) or prenatal and postnatal (n=3, originally n=15) administration of BOOST cells for the treatment of severe OI compared with a combination of historical (1-5/subject) and untreated prospective controls (≤30). Infants<18 months of age (originally<12 months) and singleton pregnant women whose fetus has severe OI with confirmed glycine substitution in COL1A1 or COL1A2 can be included in the trial.Each subject receives four intravenous doses of 3×106/kg BOOST cells at 4 month intervals, with 48 (doses 1-2) or 24 (doses 3-4) hours in-patient follow-up, primary follow-up at 6 and 12 months after the last dose and long-term follow-up yearly until 10 years after the first dose. Prenatal subjects receive the first dose via ultrasound-guided injection into the umbilical vein within the fetal liver (16+0 to 35+6 weeks), and three doses postnatally.The primary outcome measures are safety and tolerability of repeated BOOST cell administration. The secondary outcome measures are number of fractures from baseline to primary and long-term follow-up, growth, change in bone mineral density, clinical OI status and biochemical bone turnover. ETHICS AND DISSEMINATION: The trial is approved by Competent Authorities in Sweden, the UK and the Netherlands (postnatal only). Results from the trial will be disseminated via CTIS, ClinicalTrials.gov and in scientific open-access scientific journals. TRIAL REGISTRATION NUMBERS: EudraCT 2015-003699-60, EUCT: 2023-504593-38-00, NCT03706482.

A secure procedure for early career scientists to report apparent misconduct.

Early career scientists sometimes observe senior scientists engage in apparent scientific misconduct, but feel powerless to intervene, lest they imperil their careers. We propose a Secure Reporting Procedure that both protects them, when pursuing those concerns, and treats the senior scientists fairly. The proposed procedure is, we argue, consistent with the ethical principles of the scientific community, as expressed in the codes of its professional organizations. However, its implementation will require changes in procedures and regulations. Those efforts will be a small price to pay for protecting the scientific community's integrity and fidelity to its principles. We begin by describing the circumstances motivating the proposal, then sketch its design, and, finally, illustrate next steps in its application in two national settings.

[The priority-setting platform and its conditions]. / Prioriteringsplattformen kan stärka förtroendet för vården - En stötta för rättvis fördelning av våra gemensamma resurser.

The platform for priority-setting contains key ideas about the mission, goals and values of health care in Sweden. The basic idea is that health care resources should be distributed primarily according to need and effect, and secondarily according to cost-effectiveness. Nobody should be discriminated against on the basis of their gender, age, religion, ethnic origin or political views. We also need to distinguish between the health-related needs that we, as a society, have agreed should be met by publicly funded health care and needs for which there is no such agreement. The mission of health care can, and ought to, remain unchanged, even if, or as, this classification changes. The platform should not be abandoned, since it helps to maintain trust in our publicly financed health care system.

Conclusiveness resolves the conflict between quality of evidence and imprecision in GRADE.

OBJECTIVES: The objective of our article is to show how "quality of evidence" and "imprecision," as they are defined in Grading of Recommendations Assessment, Development, and Evaluation (GRADE) articles, may lead to confusion. We focus only on the context of systematic reviews. STUDY DESIGN AND SETTING: We analyze, with the aid of standard probabilistic and statistical concepts, the concepts of quality of evidence and imprecision as used in the GRADE framework. This enables us to point out some weaknesses in the relation between "quality of evidence" and "imprecision." RESULTS: The GRADE framework contains terms familiar from classical statistics, but these terms are used in nonstandard ways. Notably, "imprecision" does not have the meaning in the GRADE framework that it has in statistics, and the well-known table of "evidence levels" wrongly suggests that "quality of evidence" and "accuracy" express the same concept-they do not. CONCLUSION: We believe that "conclusiveness" rather than "imprecision" would be a suitable term to use when the question whether the CI excludes or includes certain critical margins is being addressed. Conclusiveness could also replace quality of evidence as the final step for a systematic reviewer.

Diagnostic accuracy of different caries risk assessment methods. A systematic review.

OBJECTIVES: To evaluate the accuracy of different methods used to identify individuals with increased risk of developing dental coronal caries. DATA: Studies on following methods were included: previous caries experience, tests using microbiota, buffering capacity, salivary flow rate, oral hygiene, dietary habits and sociodemographic variables. QUADAS-2 was used to assess risk of bias. Sensitivity, specificity, predictive values, and likelihood ratios (LR) were calculated. Quality of evidence based on ≥3 studies of a method was rated according to GRADE. SOURCES: PubMed, Cochrane Library, Web of Science and reference lists of included publications were searched up to January 2015. STUDY SELECTION: From 5776 identified articles, 18 were included. Assessment of study quality identified methodological limitations concerning study design, test technology and reporting. No study presented low risk of bias in all domains. Three or more studies were found only for previous caries experience and salivary mutans streptococci and quality of evidence for these methods was low. Evidence regarding other methods was lacking. For previous caries experience, sensitivity ranged between 0.21 and 0.94 and specificity between 0.20 and 1. Tests using salivary mutans streptococci resulted in low sensitivity and high specificity. For children with primary teeth at baseline, pooled LR for a positive test was 3 for previous caries experience and 4 for salivary mutans streptococci, given a threshold ≥10(5) CFU/ml. CONCLUSIONS: Evidence on the validity of analysed methods used for caries risk assessment is limited. As methodological quality was low, there is a need to improve study design. CLINICAL SIGNIFICANCE: Low validity for the analysed methods may lead to patients with increased risk not being identified, whereas some are falsely identified as being at risk. As caries risk assessment guides individualized decisions on interventions and intervals for patient recall, improved performance based on best evidence is greatly needed.