Inventarisatie van Europese methodologieën voor de risicobeoordeling van blootstelling aan chemische stoffen bij incidenten

Preventie of beperken van gezondheidseffecten bij de mens vormt de basis voor het opstellen van beleid ten behoeve van crisisbeheersing en rampenbestrijding bij chemische incidenten. Een adequate inschatting van het risico op gezondheidseffecten is essentieel voor een effectief crisismanagement. Aan de hand van een internetenquête zijn kennishiaten, behoeftes en zorgpunten van verschillende betrokken stakeholders geïdentificeerd. Het vrijkomen van acuut toxische of irriterende stoffen wordt gezien als een van de belangrijkste risicoscenario's binnen Europa. Daarnaast verwacht bijna 40% van de respondenten een toename van het aantal chemische incidenten in de nabije toekomst ten gevolge van een doelbewuste (terroristische) actie. Mogelijk kunnen ook ontwikkelingen binnen de nanotechnologie voor extra risico's bij incidenten zorgen, maar hiervoor is meer kennis nodig over de gezondheidsrisico's van nanodeeltjes. Een groot deel van de respondenten is tevens bezorgd over de gevolgen van globalisering, industrialisering en toenemende werkdruk (als gevolg van hogere efficiëntie-eisen) op het voorkomen van chemische incidenten en daarmee gepaard gaande gezondheidsrisico's. Interventiewaarden (Acute Exposure Reference Values; AERVs) worden gezien als een belangrijke instrument bij de crisisbeheersing en rampenbestrijding, hoewel een duidelijke behoefte werd aangegeven aan handvatten hoe deze waarden adequaat toe te passen. Naar aanleiding van dit onderzoek is geadviseerd om een gezaghebbende en Europees afgestemde methodologie te ontwikkelen voor de afleiding van interventiewaarden voor de rampenbestrijding en richtlijnen en trainingen te verschaffen voor toepassing in de praktijk. Hierbij is het belangrijk aandacht te besteden aan veelgebruikte acuut toxische en irriterende/corrosieve stoffen, specifieke gezondheidseffecten als carcinogeniteit en effecten op de reproductie en op nieuwe chemische stoffen. In het kader van prioriteitsstelling is verder onderzoek nodig naar nieuwe risicoscenario's van chemische incidenten.Prevention or mitigation of human health effects is often the major determinant underlying chemical incident prevention policy and emergency response decisions. The ability to perform a human health risk assessment is a prerequisite for effective chemical incident prevention, preparedness and response. To identify knowledge gaps, needs and concerns relating to health risks from chemical incidents, a web-based survey was sent to various groups of stakeholders. The release of acutely toxic substances and irritating/corrosive substances appeared to be the most important risk scenario. Almost 40% of the respondents also expected a future increase of chemical terrorism or sabotage. Developments in nanotechnology were perceived as potential future risk drivers although more information is needed on the health hazards of nanoparticles. A high number of respondents also expressed concern for the consequences of globalization, international trade and higher industry efficiency demands on health risks through chemical incidents. Acute Exposure Reference Values (AERVs) were considered important cornerstones but a need was expressed for recommendations on their use for the management of chemical emergencies. Based on this survey, it is advised to develop European consensus on an authoritative methodology to derive AERVs, to design a process for their implementation and to provide guidance and training on their practical application. Attention should be paid to the widely used acutely toxic and irritating/corrosive substances, to specific endpoints such as carcinogenicity and reproductive toxicity and new and emerging chemicals. Research should focus on developing plausible scenarios for emerging human health risks from chemical incidents to allow better prioritisation of future risk assessments

Nalmefene for Reducing Alcohol Consumption in People with Alcohol Dependence: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company (Lundbeck) marketing nalmefene (Selincro) to submit evidence of its clinical and cost effectiveness for reducing alcohol consumption in people with alcohol dependence. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG) and to produce a critical review of the company's submission to NICE. The clinical evidence was derived from three phase III, company-sponsored, randomised, double-blind, placebo-controlled trials in adults with a diagnosis of alcohol dependence comparing nalmefene, taken on an as-needed basis, in conjunction with psychosocial support with placebo in conjunction with psychosocial support. Psychosocial support was provided in the form of BRENDA, an intervention of lower intensity than that recommended in NICE Clinical Guideline 115 (NICE CG115). Post-hoc subgroup analyses were conducted in people who were drinking at high or very high risk levels at baseline and maintained this level of drinking during the screening phase prior to randomisation. This subgroup forms the licensed population. There were a number of limitations and uncertainties in the clinical evidence base which warrant caution in its interpretation. In particular, the post-hoc subgroup analyses and high dropout rates in the three nalmefene studies meant that the inference of treatment effects might be confounded. The company's economic evaluation showed that use of nalmefene in conjunction with psychosocial support in the form of BRENDA dominated the use of BRENDA in conjunction with placebo, providing more quality-adjusted life-years (QALYs) at a reduced cost. However, this evaluation did not meet the final scope issued by NICE, which specified that the comparator should be psychological intervention as defined in NICE CG115. The ERG produced alternative cost per QALY values for the comparison undertaken by the company and suggested three further comparisons deemed relevant: (1) nalmefene with psychological intervention as defined in NICE CG115; (2) delayed use of nalmefene in those who did not respond to psychological intervention as recommended in NICE CG115 alone; and (3) use of naltrexone outside of its marketing authorisation. The ERG thought it probable that using nalmefene in only those people who do not respond to psychological intervention alone was likely to be more cost effective compared with its immediate use in the entire licensed population. The Appraisal Committee accepted the comparison with psychosocial support in the form of BRENDA and believed that the most plausible cost per QALY was likely to be below £5100. Therefore, the Appraisal Committee concluded that nalmefene in conjunction with psychosocial support was a cost effective use of NHS resources compared with psychosocial support alone for treating people with alcohol dependence drinking at a high risk level, without physical withdrawal symptoms and not requiring immediate assisted withdrawal from alcohol