Harmonization Initiative Research Articles

Challenges in the Standardization of Autoantibody Testing: a Comprehensive Review.

Standardization and harmonization are complementary tools to achieve higher testing quality in laboratory medicine. Both are of great relevance and are strongly needed in autoimmune diagnostics, due to the impressive advance in basic research and technological development observed in this diagnostic field in recent years that has led to the introduction of many new tests and new analytical methods. It is, therefore, essential that this strong innovative thrust is translated into clinical practice in a coordinated way to avoid confusion and the risk of potentially harmful errors for the patient. However, while standardization of antibody assays is a very complex task, harmonization of procedures and behaviors is a more feasible target and should necessarily include all the phases of the total testing process-in the pre-analytical phase, appropriateness of test requests, harmonization of autoantibody terminology, and adoption of uniform nomenclature for laboratory tests; in the analytical phase, harmonization of measurements, and sharing of test profiles and diagnostic algorithms; and in the post-analytical phase, harmonization of data reporting, and criteria for interpreting immunoserological results, especially harmonization of units, reference intervals, decision limits, and definition and notification of critical values. We here provide and discuss some examples of harmonization initiatives related to anti-nuclear antibodies, TSH receptor, and anti-thyroid peroxidase antibodies and to antibodies associated with autoimmune hepatitis and with celiac disease. These initiatives could be the starting steps to achieve a wider consensus and a closer interaction among stakeholders in the path of autoimmune diagnostics harmonization to enhance clinical effectiveness and provide greater patient safety.

Revisiting legal harmonisation under the Southern African Development Community Treaty: The need to amend the Treaty

International trade is important for economic development across world including in Africa. Even General Assembly of United Nations has recognised that international trade is the primary instrument for economic development. This is true for Africa which continues to struggle to shake off bonds of poverty. In an effort to maximise participation in international trade, African countries have entered into various bilateral and multilateral trading agreements and arrangements with each other and with rest of world. This has culminated in various regional free trade areas and customs unions arrangements. These initiatives aim to promote movement of goods, services, capital and people within continent. However, to promote international trade, it is not adequate for them to merely focus on export promotion initiatives; is also a need to tackle impediments to trade, which includes problem of diversity of The continent's colonial legacy which introduced arbitrary borders and foreign legal traditions has made issue of harmonisation of laws even more imperative. The emergence of various legal harmonisation initiatives at regional level is testimony to need for legal harmonisation within African context. However, despite apparent legal diversity in SADC, there is not much tangible progress towards harmonisation of laws. This raises question whether this is due to lack of political will or whether there is scope for such harmonisation under SADC Treaty. This article analyses Southern African Development Community (SADC) objectives focussing particularly on whether legal harmonisation is achievable under current SADC Treaty framework. It considers question whether current SADC Treaty creates an adequate framework for effective legal harmonisation using regionally adopted community laws. It proposes amendment of SADC Treaty to make legal harmonisation one of SADC's objectives in line with similar initiatives on African continent.

Standardization in laboratory medicine: Adoption of common reference intervals to the Croatian population.

Considering the fact that the results of laboratory tests provide useful information about the state of health of patients, determination of reference value is considered an intrinsic part in the development of laboratory medicine. There are still huge differences in the analytical methods used as well as in the associated reference intervals which could consequently significantly affect the proper assessment of patient health. In a constant effort to increase the quality of patients' care, there are numerous international initiatives for standardization and/or harmonization of laboratory diagnostics in order to achieve maximum comparability of laboratory test results and improve patient safety. Through the standardization and harmonization processes of analytical methods the ability to create unique reference intervals is achieved. Such reference intervals could be applied globally in all laboratories using methods traceable to the same reference measuring system and analysing the biological samples from the populations with similar socio-demographic and ethnic characteristics. In this review we outlined the results of the harmonization processes in Croatia in the field of population based reference intervals for clinically relevant blood and serum constituents which are in accordance with ongoing activity for worldwide standardization and harmonization based on traceability in laboratory medicine.

Coping with Business Failure and Bankruptcy in the European Union. A Case Study on the Failure of Market Integration

One of the primary objectives underlying the EU was the creation of a fully integrated European single market. Initiatives regarding European integration and the furthering of the Internal Market have been more prolific in policy areas characterised by high level of transnational transactional exchanges. Initially the creation of the Single Market required the abolition of domestic rules acting as barriers to cross-border economic exchange. As the single market developed, so did cross-border dealings between companies, their shareholders and creditors. A second phase moved from abolition of barriers to harmonisation of commercial law standards to improve integration. Corporate insolvency law was seen as a fundamental part of the European economic system and therefore was brought to the fore through harmonisation initiatives. In the current crisis addressing business failure on a pan-European level is vital to the concerns of stakeholders and to wealth preservation in the EU.The paper tackles the theoretical and practical issues of the current corporate insolvency and rescue laws at European level. It addresses the difficulties facing harmonisation initiatives stemming from the fundamental distinctions that exist between domestic legal frameworks, in particular regarding the rules on business failure. The paper considers the implications of the variations that can be found in the different Member States for the harmonisation of insolvency laws at EU level. The article evaluates the adequacy of the existing European rules and analyses the current changes occurring within the EU. It especially looks at the European insolvency legal framework, notably the 2000 European Insolvency Regulation and the scope of the reform currently occurring.

Data Collection and Harmonization in HIV Research: The Seek, Test, Treat, and Retain Initiative at the National Institute on Drug Abuse.

Large-scale, multisite data sets offer the potential for exploring the public health benefits of biomedical interventions. Data harmonization is an emerging strategy to increase the comparability of research data collected across independent studies, enabling research questions to be addressed beyond the capacity of any individual study. The National Institute on Drug Abuse recently implemented this novel strategy to prospectively collect and harmonize data across 22 independent research studies developing and empirically testing interventions to effectively deliver an HIV continuum of care to diverse drug-abusing populations. We describe this data collection and harmonization effort, collectively known as the Seek, Test, Treat, and Retain Data Collection and Harmonization Initiative, which can serve as a model applicable to other research endeavors.

Current practices and reform proposals for the regulation of advanced medicinal products in Canada.

We describe the Canadian regulatory framework for evaluating advanced medicinal products based on current policies, guidance documents and regulations and analyze proposed reforms. Our analysis is based on a documentary review supplemented by discussions with Health Canada officials. We present an overview of the Canadian regulatory framework for cell and gene therapy, medical devices and manufacturing facilities. We use the approval of Prochymal™ to highlight Canada's conditional marketing approval system. Finally, we discuss proposed changes to the regulatory framework in response to identified gaps, stakeholder consultations and international harmonization initiatives. Based on our analyses, we suggest that Canadian regulators have taken a reasonable approach in applying their regulatory framework without compromising on product safety.

Promoting trade through private law: Explaining international legal harmonization

A large body of research examines states’ efforts to increase international trade through public law, that is, by forming preferential trade agreements (PTAs) that lower governmental barriers to trade. Scholars, however, have overlooked another mechanism through which states seek to facilitate trade: international harmonization of private law. Underlying legal harmonization is the assumption that cross-national variation of commercial law impedes trade; by contrast, similarity of laws across countries encourages trade by reducing uncertainty and transaction costs. I argue that the harmonization of private law acts as a substitute for the public-law channel of stimulating trade: countries with limited PTA partnerships make up for this deficiency by joining initiatives for private-law harmonization. This argument is tested by analyzing the UN Convention on Contracts for the International Sale of Goods-one of the primary instruments of legal harmonization. Indeed, countries that are party to shallow PTAs or have few PTA partners are more likely to ratify this private-law convention. Overall, this article urges scholars of trade and international law to broaden their research agenda to include private law.

Harmonisation Initiatives of Copernicus Data Quality Control

Abstract. The Copernicus Space Component Data Access system (CSCDA) incorporates data contributions from a wide range of satellite missions. Through EO data handling and distribution, CSCDA serves a set of Copernicus Services related to Land, Marine and Atmosphere Monitoring, Emergency Management and Security and Climate Change. The quality of the delivered EO products is the responsibility of each contributing mission, and the Copernicus data Quality Control (CQC) service supports and complements such data quality control activities. The mission of the CQC is to provide a service of quality assessment on the provided imagery, to support the investigation related to product quality anomalies, and to guarantee harmonisation and traceability of the quality information. In terms of product quality control, the CQC carries out analysis of representative sample products for each contributing mission as well as coordinating data quality investigation related to issues found or raised by Copernicus users. Results from the product analysis are systematically collected and the derived quality reports stored in a searchable database. The CQC service can be seen as a privileged focal point with unique comparison capacities over the data providers. The comparison among products from different missions suggests the need for a strong, common effort of harmonisation. Technical terms, definitions, metadata, file formats, processing levels, algorithms, cal/val procedures etc. are far from being homogeneous, and this may generate inconsistencies and confusion among users of EO data. The CSCDA CQC team plays a significant role in promoting harmonisation initiatives across the numerous contributing missions, so that a common effort can achieve optimal complementarity and compatibility among the EO data from multiple data providers. This effort is done in coordination with important initiatives already working towards these goals (e.g. INSPIRE directive, CEOS initiatives, OGC standards, QA4EO etc.). This paper describes the main actions being undertaken by CQC to encourage harmonisation among space-based EO systems currently in service.

Two Defining Features of Russian Tort Law: Their Rationale and Legal Effect

There are two aspects of Russian tort law that set it apart from that of other countries: the recognition of a general reversal of the burden of proof regarding fault in delictual obligations, and the existence of a general clause of strict liability. Such features are not only unique to Russian law but, also, constitute the very core of tort law in Russia today.Despite the significance of these two features, this is a gravely understudied area of research. One of the main reasons for this lies in the lack of interest in (and access to) Soviet legal literature and case law. However, without examining such sources, it is impossible to grasp the rationale behind such atypical legislation, which in turn, makes it difficult to understand Russian tort law in general. Therefore, it is necessary to explore the legislative history of Russia’s past era.Equally important is the legal effect that features may have in modern Russian tort law. This article will focus on the impact that a general reversal of the burden of proof has had on the outcome of tort cases in Russia. The author also will compare the general clause of strict liability in the Russian Civil Code with the regulation of sources of heightened danger in selected countries, a topic that deserves special attention, given Russia’s extensive experience in the field. In addition, all these questions will be examined against the backdrop of other contemporary jurisdictions and European harmonization initiatives in the area of tort law.

Harmonizing influenza primary-care surveillance in the United Kingdom: piloting two methods to assess the timing and intensity of the seasonal epidemic across several general practice-based surveillance schemes.

General Practitioner consultation rates for influenza-like illness (ILI) are monitored through several geographically distinct schemes in the UK, providing early warning to government and health services of community circulation and intensity of activity each winter. Following on from the 2009 pandemic, there has been a harmonization initiative to allow comparison across the distinct existing surveillance schemes each season. The moving epidemic method (MEM), proposed by the European Centre for Disease Prevention and Control for standardizing reporting of ILI rates, was piloted in 2011/12 and 2012/13 along with the previously proposed UK method of empirical percentiles. The MEM resulted in thresholds that were lower than traditional thresholds but more appropriate as indicators of the start of influenza virus circulation. The intensity of the influenza season assessed with the MEM was similar to that reported through the percentile approach. The MEM pre-epidemic threshold has now been adopted for reporting by each country of the UK. Further work will continue to assess intensity of activity and apply standardized methods to other influenza-related data sources.

The journey toward quality and patient safety in laboratory medicine continues.

Errors in laboratory medicine have a completely different meaning today than they had a century ago. At that time, the term referred to defects in the analytical performance of the test itself, the so-called analytical phase.[1] A dramatic change in addressing the issue of errors in laboratory medicine started at the end of the 1990s, when a body of evidence has been accumulated demonstrating vulnerability in the pre- and postanalytical phases.[2,3] The study by Abdollahi and co-workers confirms that more than 50% of errors are related to preanalytical steps, with 23.2% of errors in the intraanalytical and 11.7% in the postanalytical phase, respectively.[4] In addition, this study provides further evidence that the frequency of errors in inpatients is significantly higher than in outpatients due to several problems: Not always standard operating procedures (SOP) for test request, sample collection, handling, and transportation are followed by healthcare personnel who are not under the direct control of the laboratory; The complexity of some preanalytical steps (namely blood drawing) is higher for inpatients, due to age and disease issues; The trend toward consolidation and commoditization of laboratory services is decreasing the quality of communication between clinicians and laboratory professionals. The “take-home” message is the need to consensually develop and adopt SOP for safely performing patient identification and preparation, test requesting, sample collection and handling and that harmonization initiatives should be performed to improve procedures and processes at the laboratory–clinical interface. It seems likely that only a small proportion of laboratory errors results in actual patient harm and adverse events thanks to the several barriers and defensive layers present between the release of laboratory information, the decision-making process and, ultimately, the action on the patient. However, from a risk management viewpoint, even the great majority of laboratory errors with little direct impact on patient care provide important learning opportunities. In fact, any error, regardless of its apparent triviality, might indicate weaknesses in policies and procedures that may not lead to adverse events in their particular context, but might cause the patient harm in slightly different circumstances. An important step in the journey toward the reduction of the error rates in laboratory medicine is the implementation of a valuable quality system according to the International Standard ISO 15189:2012 and of reliable quality indicators (QIs) covering all steps of the intra- and extra-analytical phases of the total testing process (TTP).5 It has been demonstrated that performance and outcome measures improve the quality of patient care and, in particular, QIs represent valuable tools for quantifying the quality of selected aspects of care by comparing it against a defined criterion. The measurement and monitoring of QIs in laboratory medicine serve many purposes as they make possible to: Document the quality of the service provided; Improve performance and patient safety; Make comparison (benchmarking) over time between laboratories; Make judgments and set priorities (corrective actions to be performed); and Support accountability, quality improvement and accreditation. Recently a set of QIs has been consensually defined to allow clinical laboratories to measure and improve the quality of all steps of the TTP. The journey toward quality and patient safety continues.

A framework for the geometric accuracy assessment of classified objects

European initiatives for data harmonization and the establishment of remote-sensing-based services aim at the production of up-to-date land-cover information according to generally valid standards for the accurate qualification of thematic classification results. This is particularly true since new satellite systems provide data of high temporal and geometric resolution. While methods for point-related thematic accuracy assessment have already been established for years, there is a need for a commonly accepted framework for the geometric quality of tematic maps. In this study, an open and extendable framework for the geometric accuracy assessment is presented. The workflow begins with the definition of basic geometric accuracy metrics, which are based on differences in area and position between samples of classified and reference objects. The combination of user-defined metrics enables both a geometric assessment of single objects as well as the total data set. In an example of thematically classified agricultural fields in a German test site, we finally show how object relations between classified and reference objects can be identified and how they affect the global accuracy assessment of the total data set.

Promoting clinical and laboratory interaction by harmonization

The lack of interchangeable results in current practice among clinical laboratories has underpinned greater attention to standardization and harmonization projects. Although the focus was mainly on the standardization and harmonization of measurement procedures and their results, the scope of harmonization goes beyond method and analytical results: it includes all other aspects of laboratory testing, including terminology and units, report formats, reference limits and decision thresholds, as well as test profiles and criteria for the interpretation of results. In particular, as evidence collected in last decades demonstrates that pre-pre- and post-post-analytical steps are more vulnerable to errors, harmonization initiatives should be performed to improve procedures and processes at the laboratory–clinical interface. Managing upstream demand, down-stream interpretation of laboratory results, and subsequent appropriate action through close relationships between laboratorians and clinicians remains a crucial issue of the laboratory testing process. Therefore, initiatives to improve test demand management from one hand and to harmonize procedures to improve physicians' acknowledgment of laboratory data and their interpretation from the other hand are needed in order to assure quality and safety in the total testing process.

The ICH, the GHTF, and the Future of Harmonization Initiatives.

Comparison of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and the Global Harmonization Task Force (GHTF), the global regulatory harmonization initiatives in the field of drugs and medical devices, respectively, reveals that "harmonization" activities contain several categories. It was also found that the target level of harmonization (ie, that of technical regulatory requirements and that of regulatory processes) greatly affects the implementability of final work products. Those products concerning regulatory processes (most of the GHTF Documents) often require legal changes and are more difficult to implement than those regarding technical requirements (all of the ICH Guidelines), usually implementable by regulatory authorities publishing them as nonbinding suggestions. Globalization of medical product development, manufacture, and distribution increasingly requires regulatory cooperation across borders, which inevitably affects the initiatives. Identifying what "harmonization" each harmonization initiative aims at is indispensable in determining future directions.

Product Registration in Developing Countries: A Proposal for an Integrated Regional Licensing System Among Countries in Regional Economic Blocs.

The product pipeline for diseases that disproportionately affect the developing world has considerably expanded over the last decade. Indeed, there are about 134 products for these diseases in the pipeline, including vaccines, drugs, diagnostics, microbicides, and vector control tools, and dozens of these products are currently being evaluated in human trials in developing countries where the disease of interest exists. While these efforts are underway, the need to identify regulatory pathways for licensing these new products is becoming obvious to many manufacturers. In many developing countries, where the need of these products is greatest, the national regulatory authorities often lack the resources and regulatory capacity to review the registration dossiers to approve the use of new products. Given this challenge, new regulatory models are urgently needed to offset product registration. In this paper, we propose how regional regulatory frameworks established by regional harmonization initiatives can be used to set up an integrated regional licensing system, a system that will provide for a single product dossier application and a single review, leading to a single approval that will grant access to all the markets in the region. The proposed model aims at complementing the ongoing regional regulatory harmonization efforts by pooling the activities of different national expertise groups so as to make the best use of the available skills at a reduced cost. By sharing the various regulatory tasks in an integrated manner, the total process will be accelerated and will facilitate product registration in the region.

The Red Tape Waltz

How could it happen that the very processes intended to assure ethical research in Australia might, themselves, undermine good research practice? This paper describes one PhD candidate's recent experiences of multi-centre review for a Human Research Ethics Committee approved, low/negligible risk, qualitative study, at the crossroad of health services research and organisational research. A retrospective review of international literature about multi-centre review processes revealed that many of these experiences were not unique and might have been expected, notwithstanding Australian efforts at harmonisation of multi-centre review. This paper examines not only the burden of red-tape that was applied to a small doctoral study, but also the way in which the red-tape threatened the anonymity of potential study participants and risked exposing them to undue pressure and distress. These experiences support the view that harmonisation initiatives have not yet developed as the Australian National Health and Medical Research Council may have hoped and that further attention is needed to harmonise research governance processes.

The Long and Winding Road to OHS Harmonisation

Australia’s harmonised occupational health and safety (OHS) regulatory regime was scheduled to commence 1 January 2012. Presently, however, only seven (out of nine) jurisdictions have enacted harmonised laws, most with differences. That the harmonisation initiative has not (yet) delivered on its promise should not have come as a surprise to those familiar with the history of OHS harmonisation in Australia - a history punctuated by moments of great hope followed by disappointing progress. This article examines this history through the lens of Australian federalism. In doing so, it illustrates the organic growth in the Commonwealth’s sphere of responsibility as matters originally defined as social issues become redefined as economic issues in that they negatively impact on business interests. It also demonstrates the tensions that arise when these economic values come into conflict with the values underpinning Australian federalism and OHS regulation itself.

Designing an adaptive phase II/III trial to evaluate efficacy, safety and immune correlates of new TB vaccines in young adults and adolescents

This article summarises the consensus arrived at a meeting of South African and international stakeholders on specific late phase clinical trial design issues integrating the investigation of immune correlates as an integral part of a phase III protocol for a preventative TB vaccine in an adolescent/adult population. The challenge ahead is to optimize the planning for phase 3 TB vaccine preventative trials, under resource constraints, given that there are no known correlates of protection to shorten and increase the efficiencies of efficacy trials. An adaptive, multi-arm, group sequentially designed trial protocol is proposed incorporating design features that address uncertainties arising from both advances in the field and dynamic study populations and disease states. Such a design allows modifications that protect research subjects, save time, and maximize the impact of scarce financial resources. Further, the protocol underwent joint review by regulators from several African nations at a meeting of the African Vaccine Regulatory Forum (AVAREF), a regional regulatory harmonization initiative, and recommendations are included.

Some Implications of IFRS Adoption for Accounting Education

This paper addresses challenges accounting educators face in their teaching following the adoption of International Financial Reporting Standards (IFRS). We use Australia as an example of a developed nation and 2005 adopter of IFRS, the United States as a potential adopter, and Romania as an emerging economy with a history of harmonisation and adoption initiatives. Accounting educators globally need to strengthen their engagement with the principles‐based approach to teaching IFRS. Teaching resources, educational research and Continuing Professional Development activities related to a principles‐based approach to teaching IFRS are necessary for educators to enrich the learning experience of students given the move from a rules‐based to a principles‐based set of accounting standards.

A systematic review with attempted network meta-analysis of asthma therapy recommended for five to eighteen year olds in GINA steps three and four

BackgroundThe recommendations for the treatment of moderate persistent asthma in the Global Initiative for Asthma (GINA) guidelines for paediatric asthma are mainly based on scientific evidence extrapolated from studies in adults or on consensus. Furthermore, clinical decision-making would benefit from formal ranking of treatments in terms of effectiveness.Our objective is to assess all randomized trial-based evidence specifically pertaining to 5-18 year olds with moderate persistent asthma. Rank the different drug treatments of GINA guideline steps 3&4 in terms of effectiveness.MethodsSystematic review with network meta-analysis. After a comprehensive search in Central, Medline, Embase, CINAHL and the WHO search portal two reviewers selected RCTs performed in 4,129 children from 5-18 year old, with moderate persistent asthma comparing any GINA step 3&4 medication options. Further quality was assessed according the Cochrane Collaboration’s tool and data-extracted included papers and built a network of the trials. Attempt at ranking treatments with formal statistical methods employing direct and indirect (e.g. through placebo) connections between all treatments.Results8,175 references were screened; 23 randomized trials (RCT), comparing head-to-head (n=17) or against placebo (n=10), met the inclusion criteria. Except for theophylline as add-on therapy in step 4, a closed network allowed all comparisons to be made, either directly or indirectly. Huge variation in, and incomplete reporting of, outcome measurements across RCTs precluded assessment of relative efficacies.ConclusionEvidence-based ranking of effectiveness of drug treatments in GINA steps 3&4 is not possible yet. Existing initiatives for harmonization of outcome measurements in asthma trials need urgent implementation.