Centralised Procedure Research Articles

Building quality measures into the regulatory review process

The Centre for Medicines Research (CMR) in the UK has produced a publication based on its 17th workshop that dealt with quality in the regulatory process [1], which was a logical sequel to the 16th workshop on the clinical dossier [2]. In some ways, it is a companion piece to the recent EMEA/IFAPP conference [3]. As stated in the foreword, the quality of the review process is inseparable from the quality of the submitted dossier and, in turn, the latter depends on the quality of the work performed. However, this simplistic linkage fails to differentiate between the factual basis of the work and of the dossier, on the one hand, and the opinions expressed by experts and the decision-making process in the regulatory review, on the other. After all, the same dossier is reviewed by different regulatory agencies, and the fact that each may identify and/or focus on one or two different issues from the others surprises people in the industry, who have seen this scenario many times. Possible reasons for any divergence was illustrated by the first contribution describing the findings of a CMR International Study. In 1999, the CMR sent a questionnaire to ten major regulatory authorities, of which nine responded. While most agencies provided training for their reviewers and collaborate with each other in training, there was a marked difference in training for external experts and advisory committee members, who make the decisions. Only one agency provided such training. Another difference in practice between authorities was the fact that, in half the cases, Advisory Committees reviewed only selected dossiers, while in the rest all were reviewed. In six authorities, the reviews only covered the assessment reports and only in one was the complete dossier reviewed. Five agencies have extensive contact with sponsors during development and four during the review process. One agency has no contact with the sponsor during development and another has no contact during the review process. A second paper presented an analysis of the outcomes of the European Union Centralized Procedure between 1995 and 1999. The main findings were the rise in the number of negative outcomes, primarily due to withdrawals of the submissions when the applicant received the list of questions, peaking in 1998 (41%) and falling slightly in 1999 (31%). The major negative decisions were based on clinical efficacy, mainly due to their design and the doubtful the robustness of pivotal data, and on clinical safety, where increased mortality and other serious adverse events activated those decisions. There was a positive concordance between the Food and Drug Administration (FDA) and the EMEA on positive decisions, but additionally the FDA approved 35% of applications that had a negative EMEA outcome. The FDA’s recent actions were presented in another paper that described the enhanced performance goals and the Good Review Practice (GRP) initiative. The latter was launched in 1994 and it has examined clinical holds and refusals to file and is setting guidelines in order to achieve consistency and uniformity. It has provided training for Advisory Committee members, although it is not mandatory. The syndicate groups and the workshop discussion addressed the differences in quality assurance methods employed by various national authorities and the impact of them. It also looked at the quality of the dossier on the quality of the review process. The key recommendations included global standards, clarification of questions during the review process, and regulators using review templates. The industry should check the quality of the dossier, provide a ‘road map’ in dossiers to orientate reviewers, and provide early label proposals and supporting studies for them.

Which post-marketing database and studies does EMEA require

The European process for assessment of pharmaceutical products is complex and presents with different levels. There is the European level with two major procedures resulting in decisions on approval after...

Some features of two fieldbuses of the IEC 61158 standard

The IEC 61158 is on the way to become an international fieldbus standard after a long period of contrasts and misunderstandings. The final standard document results from the joining of eight among the most diffused fieldbus protocols. This paper takes into consideration one of the most popular fieldbus of the final standard document, Profibus, and examines the differences with the original IEC 61158 Technical Specification (which is also included in the standard). The analysis concerns the data link layer of the two fieldbuses: Profibus is based on a token passing technique, while the IEC fieldbus realises a mixed access combining token passing with a centralised scheduling procedure managed by a special node named Link Active Scheduler (LAS). Two parameters of the data link layers have been in particular considered: the cycle time and the medium access efficiency. In particular, the evaluation of the cycle times has been carried out using analytical models which are valid under the hypothesis that the token holding times of the stations are sufficiently long to satisfy all the service requests coming from the users, that is a typical situation of a network not overloaded. Considerations have also been made to investigate the behaviours of the cycle times when the network traffic increases.

Safeguarding Europe-Wide Patent Protection: the European Patent Office

The European patent system, created in 1977, provides for the co-existence of a national and a centralised procedure for the grant of patents. Central grant authority for European patents is the European Patent Office in Munich, which carries out its task on the basis of the provisions laid down in the European Patent Convention. The establishment of a Europe-wide patent system has led to a significant increase in the demand for patent rights in Europe. In the framework of their co-operation, the member states of the European Patent Organisation have also created a unique patent information network for accessing the information contained in patent documents. In view of its impending eastward expansion, the European Patent Organisation is set to undertake a revision of the European patent system to ensure its flexibility in the future.

Centralized Retention Strategies in the Multi-Center Women's Intervention Nutrition Study (WINS)

High attrition rates in large-scale clinical trials can ultimately result in decreased statistical power. WINS is a randomized trial with a recruitment goal of 2,500 women, evaluating the influence of dietary fat intake reduction on breast cancer recurrence, conducted at 38 clinical sites. To date, WINS has enrolled 1735 participants, with a 7.7% “inactive” rate (56% low-fat intervention group, 44% control group). Reasons for attrition include: unable to contact/not interested (23.8%), other medical/family problems (16.4%), caring for sick relative (9.7%), cancer recurrence (8.9%) (participants with a recurrence are encouraged to remain in the trial), too busy (7.5%), and wanted to be in the intervention group (7.5%). In response to an identified need to implement behaviorally oriented retention strategies study-wide, local and centralized procedures were developed by the WINS Intervention Unit (IU). Working with all clinical sites, the IU facilitates ongoing communication and development of local action plans for retention problems. In addition, the IU identifies “inactive” participants refractory to local clinic strategies, collects background information on such participants from clinical site Nutritionists, and via telephone, implements retention strategies by a behaviorally trained Nutrition Intervention Coordinator (NIC). During this contact, the NIC discusses participant's concerns and attempts to negotiate a compromise resulting in study continuation, such as taking “time-off” from the study or participation in a modified capacity. Following recent implementation, approximately 2-4 participants/month have been identified as candidates for this intervention. Data collection procedures are in place to evaluate effectiveness. A centralized IU can be used to develop local retention action plans and deliver behaviorally oriented telephone interventions in a large-scale clinical trial. The effectiveness of this approach is currently under evaluation.

Business Networking in the Swatch Group

As part of ‘The Swatch Group’ ETA SA supplies watch movements and spare parts to all Swatch brands and other customers such as retailers and watchmakers. To improve the quality and the efficiency of the customer relationships ETA started a Business Networking project in cooperation with the University of St Gallen. This project focused on the complementary application of two Business Networking strategies that are usually treated separately: supply chain management and electronic commerce (e-commerce). Both concepts allow for establishing direct relationships to the customers. Supply chain management enables direct deliveries to the customers at lower costs and improved reliability. E-commerce provides centralized catalogues and order entry procedures with significant advantages in time and cost. This highlights the importance of understanding the interrelations between both strategies in creating mutual benefits between ETA and their customers.

The EC novel foods Regulation—a UK perspective

On 15 May 1997 the EC novel foods Regulation came into effect introducing a statutory pre‐market approval system for novel foods across the whole of the European Union. A novel food is defined as a food which has not been consumed to a significant degree and includes foods containing or obtained from genetically modified organisms. The Regulation envisages an initial safety assessment at Member State level, although centralized procedures are available to resolve any objections between Member States. The most controversial aspect of the Regulation relates to the provisions for labelling genetically modified foods. Within the framework of the Regulation there is scope for labelling to be considered on a case by case basis, although the UK is pressing for all foods which may contain genetically modified material to be clearly labelled. To ensure that all Member States follow a consistent approach to the safety assessment of novel foods, the Commission has published a series of guidelines to accompany the regulation. The UK already has a well‐developed system for assessing the safety of novel foods dating back to the approval of the first novel food in the UK in 1983.

Brown's procedure for congenital absence of the tibia revisited.

The results of reconstructive surgery in tibial hemimelia using a modified fibular transfer procedure as described by Brown were reviewed. A modified Brown's procedure was carried out on five patients with a total of seven affected limbs. A Syme's-type amputation of the foot was carried out in each case. All of the knees had quadriceps function preoperatively, which was considered a prerequisite for surgery. Average length of follow-up was 7 years, with a range of 2-12 years. The average age at time of surgery was 12.7 months, with a range of 7-26 months. At the time of review, all patients had reasonably good function of their lower extremities. All were ambulating with patellar tendon-bearing prostheses and thigh extensions for collateral support. The average arc of motion at review was 57.4 degrees, with further passive motion possible in all cases. Average extension was -18.5 degrees, and the average active flexion was 76 degrees. We found that a fibular centralization procedure in a patient with at least grade III+ quadriceps function can give good functional results that do not appear to deteriorate over time.

Experience with the Concertation Procedure: Bridge to the Centralized Procedure

The concertation procedure has been a success in many respects, and will serve as a bridge to the future centralized procedure in the EC. Since the procedure's implementation, the distribution of rapporteurs has become evenly spread among Member States. Approval rates for products using this system have been quite high. One major success of the concertation procedure is that it has brought Member States closer together. It will also ease the transition to a centralized procedure.

Regulation and abuse liability testing of medicines in Europe beyond 1992

The procedures for approving medicines have been progressively harmonized within the European Community. The authorization of medicinal products beyond 1992 will be based on a more centralized procedure, with important safeguards to ensure that there is no dilution of strict standards of quality, safety, and efficacy. Although some efforts have been attempted to coordinate the procedures for approving medicines with Japan and the United States, some important problems still remain. An example of this lack of coordination is the lack of agreement about applying abuse liability testing to psychotropic drugs. In the United States, abuse liability data are routinely used for scheduling and labeling new drugs under the supervision of the Food and Drug Administration (FDA). This agency has codified the requirements for clinical studies of potential abuse of psychotropic drugs and requires pharmaceutical sponsors to submit specific data. However, requirements within the European Community in this matter are minimal. Clinical trials on subjective effects, drug discrimination or drug preference are not requested. This situation demands more scientific interchange between officials and scientists from the FDA and their counterparts from Europe. The Committee for Proprietary Medicinal Products (CPMP) must play a major role in this coordination and interchange.

District general manager's perspective

need for the ENB and the CNAA together to sponsor a series of workshops around the country designed to familiarise college lecturers and nurse tutors with the different procedural requirements and expectations entailed in academic and professional validation. However, the complexities and difficulties experienced in conjoint validation are also an expression of more profound divergences in philosophy and approach between the two sectors. The recent decision by the ENB to embrace the idea of peer review as an integral part of the validation process and to establish a register of specialist visitors has been widely welcomed in HE. However, I believe that the board will need to modify further its highly centralised approval procedures, particularly if Schools of Nursing are to be linked ever more closely to accredited HE institutions that may well be awarding their own degrees and diplomas within the next few years. Secondly, we must recognise that the impact of the proposals contained in the NHS White Paper ‘Working For Patients’, together with the consequences of the ideas expressed in Working Paper 10, are likely to make HE institutions more hesitant in becoming involved in new collaborative ventures with DHAs. HE institutions are rightly concerned at the proposed transfer of responsibilities for the funding of nursing and paramedical education to regional health authorities. On the one hand, it is not clear that the close relationships that have developed between colleges, Schools of Nursing and DHAs will be able to be recreated at the level of the RHA. On the other, the majority of HE institutions will be extremely reluctant to participate in yet another system of competitive tendering in an attempt to secure education and training contracts from regions. Finally, we have to recognise that the plans to create an internal market within the NHS are also likely to undermine the enthusiasm of HE institutions for participating in major new initiatives in nursing education, at least during the transitionary period. At the present time, many of the costs of expensive clinical and community placements, together with the associated costs of teaching and supervision in these placements, are ‘lost’ within the system. Whether these hidden educational subsidies will continue in the future is uncertain. The thought that, in a few years time, independent hospital trusts could be insisting that higher education corporations cover the full costs of clinical and community placements is likely to deter rather than encourage future collaborative ventures in the field of nurse education.

A centralization procedure for radial clubhand

A modified centralization procedure for radial club hand caused by partial or total absence of the radius is presented. This technique differs from the methods presently used in that no carpal bones are resected. Adequate release of the wrist from the fibrotic radial anlage is provided through two Z-plasty incisions to allow the hand to move easily to the new position. Stabilization is then obtained with a Kirschner wire placed via the lunate and capitate into the long finger metacarpal and then directed in a retrograde fashion into the ulna. A total of 12 centralization procedures with the above technique have shown very good results. Long-term follow-up results demonstrate remodeling of the ulna, which becomes broad in its distal end, resembling a radius.

Access to Higher Education in the Federal Republic of Germany: theNumerus Claususissue

The issue of access to higher education is one which arises periodically in educational planning in any country. Relevant questions within the issue include how overcrowding at universities should be dealt with, whether there should be a restriction of university admissions (a Numerus clausus) and if so, on what basis. In the Federal Republic of Germany this issue has assumed a particular importance during the last two decades, because of certain educational traditions and constitutional guarantees. The first of these was that anyone who had obtained the Abitur (grammar school leaving certificate) had almost always been able to, and usually did, proceed automatically to university, and indeed to any university of his choice, by applying there directly to study his chosen subject. No centralised admissions procedure took place. This tradition was confirmed in article 12, paragraph I of the Grundgesetz (Basic Law, the constitution of the Federal Republic), which guarantees the individual a free choice of profession and place of education. Another aspect of this system was that the Abitur was not a centralised examination, either on federal or on Land [1] level, and that, beyond the fact of pass or failure, the actual marks obtained in the Abitur were of little importance for university entrance. A further German tradition which is significant in this context is that of academic freedom within the university for both professors and students. For professors and lecturers this meant the right to lecture on topics of their choice and for students the right not only to construct their own courses from lists of lectures and seminars but also to study for as long as they felt it to be necessary before taking their final examinations. These traditions and guarantees did not make access to higher education a contentious issue until the 1960s, because until then the percentage of young people going to university was relatively small, about 8% of 19-21-year-olds in 1960 [2]. However, during the 1960s and 1970s student numbers rose dramatically, much more quickly than had been forecast. The Wissenschaftsrat (Council for Sciences and Humanities) predicted a rise in the number of German national students from 193,000 in 1960 to between 205,900 and 281,000 by 1976/77 [3]. In fact by the academic year 1976/77 the total number of German national students, excluding those at Fachhochschulen (advanced vocational colleges), had reached 678,200, and two years later the figure was 729,500 [4]. And by 1974, when the controversy over Numerus clausus was at its peak, 18% of 19-21-year-olds were entering university [5]. Apart from the rise in the birth rate which should have been taken into account in the forecasts, there were three main reasons for this massive increase in the number of students.

From Containment To Conflict? Social Planning In The Seventies

ABSTRACTDuring the 1970s a complex range of formal planning procedures were developed by central and local government and other public bodies. By the end of the decade there were well over twenty ‘public planning systems’ in operation, each with its own timetable, procedure and information demands. A number of allocation formulae were evolved to distribute cash and capital allocations between geographical areas, and various procedures to improve service coordination were also introduced. Together these innovations have had an important impact on the allocation of social service resources and the implementation of social policies. The first part of the article describes the growth of such planning activities, while the second part seeks to analyse their purposes both in terms of the official accounts and from a rather more critical perspective. It is possible to see these changes as attempts by government to come to terms with the problem of ‘overload’ – the tendency for demands on government for more and better services to outrun its and the economy's capacity to respond. They may be seen as more explicit and centralized rationing procedures which seek to combine a realistic appreciaation of budgetary constraints with responsiveness to varied individual and community needs. Critics see these procedures as attempts to contain public spending by insulating popular demands for improved services in increasingly technical and centralized procedures. The article ends by considering the impact of the new government's public expenditure policy.