‘Emerging risks’ identified as first of four key stages in a risk cycle

Assigning risk ownership is not always simple, especially where the risk sits across different areas of responsibility

Risk governance tends to be adapted to routine risks, rather than emerging risks, which can evolve rapidly, affecting multiple stakeholders across geo-political boundaries. For example, unforeseen events such as the 2007 financial crisis and 2011 Fukushima disaster have highlighted how the world can quickly change without warning, with no set procedures in place for managing the effects.

Despite this awareness, the literature review found no unified, usable definition of emerging risks that could help policymakers with a framework for managing them. For example, in some definitions, an emergent risk is simply one that a stakeholder has failed to recognise so far, therefore preventing the calculation of probabilities and expected loss. Others emphasise that the risk will have an impact in the next one to five years, making them a priority for action over longer-term risks.

Some organisations highlight the dynamic nature of a risk portfolio, due to new technology, processes, discoveries or behaviours. For example, the European Food and Safety Agency (EFSA) connects emerging risks to newly identified hazards or increased exposure to known hazards. Uncertainty and magnitude of consequences also feature in definitions, yet these can also be associated with risks that are not emerging — thus they are not unique characteristics.

Instead of a type of risk, the study proposes that emerging risks in fact describe a stage in the risk cycle prior to full recognition at the scientific or societal level; at some point, every risk has been ‘emerging’. To deal with the real and socially constructed challenges posed by emerging risks — to mitigate or prevent their consequences — policymakers need to develop capabilities in signal detection and foresight.

The path of risk emergence can go through one or all of three states before reaching full emergence:

  • Ontological
    when combinations of activities and stakes (societal values) with potentially negative outcomes are modified, or when new combinations occur. These risks can be totally hidden from human perception (‘unknown unknowns’) until a change occurs. For example, asbestos has been used for at least 2 000 years, but the first death related to it was only officially recorded in 1906.
  • Epistemological
    when science highlights that an activity poses a threat, although the risk is uncertain and long-term studies are needed to gather evidence of the risk. For example, scientific literature recognises the risk of cancer from exposure to electromagnetic fields, but the extent of this risk is subject to conflicting evidence and only acknowledged by the World Health Organization as a possible carcinogen.
  • Societal
    where a risk is officially recognised, as well as the necessity for dedicated policies, responsibilities and acceptability levels. This stage does not necessarily follow ontological or epistemological emergence, but can be the result of social pressure or the application of the precautionary principle. For example, following the latter, France banned the endocrine disruptor Bisphenol A in 2012, although the EFSA states that exposure levels do not present a health risk.
  • Fully emerged
    where both scientific communities and policymakers agree there is a need to deploy appropriate risk policies, and scientific evidence continues to confirm the need to take action. The researcher argues that public debate on risks in the societal state are not necessarily influenced by scientific knowledge, but ‘fully emerged risks’, e.g. climate change, are confirmed by scientific evidence.

Risk ownership is highlighted at both the epistemological and societal stages. Insurance contracts and court decisions can set precedents with regards to responsibility, even where risks are scientifically controversial. For example, a French court awarded damages to a victim of electro hypersensitivity syndrome in 2015, for the first time. This sends a clear signal that there is a need for regulators and stakeholders to adopt a position on emerging risks even at the scientifically controversial stage. To base governance on scientific evidence, policymakers should make decisions on who holds responsibility for the risks related to novel activities and substances, e.g. nanoparticles, before the debate reaches the societal stage.

This approach invites policymakers to focus on risks at the ontological and epistemological stage in order to manage outcomes. Successfully detecting and interpreting early signals of change can even prevent negative effects of hidden risks. Moreover, the development of foresight capabilities can provide valuable analysis of risks and opportunities that may appear in the future. Both these techniques are fundamental for policymakers when defining the appropriate strategies for managing emerging risks.

Assigning risk ownership is not always simple, especially where the risk sits across different areas of responsibility. With such risks, when no single entity is officially in charge, the risk can be ‘orphaned’, resulting in no action. Governing the risks of global warming and other cross-boundary environmental issues requires going beyond national governance structures. For policymakers, this means long-term planning, co-ordination and collaboration across managerial levels.

Sources and More Information
  • (Re) Defining Emerging Risks, wiley online library, DOI: 10.1111/risa.12759, 2017-03-21.
  • ‘Emerging risks’ identified as first of four key stages in a risk cycle, Science for Environment Policy, Issue 495, 14 September 2017.
  • Featured image credit cerasis.

(Re) Defining Emerging Risks

‘Emerging risks’ identified as first of four key stages in a risk cycle

The phrase ‘emerging risk’ has been widely used in scientific and business communities, but without consensus on how to define and govern such a risk. A new study proposes that risk emergence goes through four states, from ‘unknown unknowns’ to risks that are fully in the public domain. Understanding emergence as a process can help decision makers detect and manage risks on the basis of scientific evidence.

Study Abstract

The concept of emergence in risk management can be seen as a revealing symptom of the increasing need for organizations to update their portfolio of risks and opportunities in a rapidly changing and highly competitive environment. Accordingly, the concept of emerging risks has been widely discussed in both scientific and business communities, with, however, a lack of agreement as to whether we should distinguish these risks from others and, if so, what should be the adopted approach for their governance. After reviewing a large set of definitions and conceptions of emerging risks, this article aims at exploring the existence of distinctive features allowing the characterization of a risk as emerging or not. First, we will demonstrate that the features used in the various definitions are ineffective to achieve this distinction. Furthermore, we will argue that all events and consequences associated with risks are or have been states of nature that emerged from complex interactions involving combinations of hazardous activities and stakes. Accordingly, emerging risks are no longer a specific category of risks; they are rather an early step in every risk life cycle that deserves specific governance approaches.

Sources and More Information
  • (Re) Defining Emerging Risks, wiley online library, DOI: 10.1111/risa.12759, 2017-03-21.
  • ‘Emerging risks’ identified as first of four key stages in a risk cycle, Science for Environment Policy, Issue 495, 14 September 2017.
  • Featured image credit insurancejournal.

When is it time to stop debating and accept the evidence ?

Via “An Taisce” charity, dedicated to protecting Ireland’s natural and built heritage

An appropriate cartoon for the Paris Agreement ratification and no-fracking day in IRL. Will @FineGael try to block efforts to ban fracking?

Image source @AnTaisce, 27 oct. 2016.

Call on MEPs to protect us all from the real dangers of endocrine disruptors

Tell the Members of the European Parliament to put public health before corporate profits and ban harmful EDCs

Monsanto, Bayer, and BASF are about to score a major win by keeping toxic endocrine disrupting chemicals (EDCs) that poison our health off the radar.

Recently, a majority of EU member countries accepted a European Commission legislative proposal on EDCs that would leave us vulnerable to these toxic substances — especially children and pregnant women most susceptible to EDCs.

Experts are slamming the proposal, which sets criteria for which chemicals get classified as EDCs. They say it sets the burden of proof of harm so high that most of these harmful chemicals will go unregulated.

Even more, this dangerous text is now in danger of becoming law throughout the EU.

But it’s not over yet. The Commission’s proposal must now be approved by the European Parliament on 3 October, which means there’s still time for our voices to be heard.

Call on MEPs to block the European Commission’s proposal to identify EDCs that leaves us vulnerable to unregulated chemicals.

EDC’s are linked to hormone-related cancers, birth defects, and other serious developmental disorders.

Besides requiring a level of proof to identify a chemical as an EDC that is way too high, the text proposed by the European Commission also foresees unacceptable exemptions. Moreover, it is limited to endocrine disruptors in pesticides and biocides, while these toxic substances hide everywhere –- from our cosmetics and food packaging, to medical devices used in hospitals.

Nearly half a million SumOfUs members and supporters of the EDC-Free Europe coalition have been standing up to the dangerous EU commission proposal on regulating these chemicals already.

It’s time to channel that same energy and remind MEPs from all over Europe that they should put the health and voices of citizens like you before the interests of Bayer and Monsanto lobbyists.

Call on the Members of the European Parliament (MEPs) to listen to the facts and reject the Commission’s dangerous proposal for endocrine disrupters.

While companies like Monsanto make money off of them, EDCs cost society an estimated 163 billion euros per year in Europe.

But the agrochemical industry is trying to drown out the voices of concerned scientists, public health experts and citizens, with an army of lobbyists in Brussels.

SumOfUs and EDC-Free Europe coalition members have already achieved major victories in the fight against toxic products in Europe. Because we keep coming together to take action, the renewal of toxic pesticides like glyphosate keeps being postponed.

Now, it’s time to pool our efforts once again to remind MEPs to put public health before the profits of Monsanto and Bayer.

We don’t have a moment to lose — the decisive vote will be held in Parliament in just a couple of weeks!

Tell our MEPs to prioritise citizens’ voices over corporate interests and to protect us all from the real dangers of endocrine disruptors.

Endocrine Disruptors
An Investigation
  1. The Manufacture of a Lie.
  2. A Denial of the State of the Science.
  3. The Interference of the United States.
  4. The Discreet but Major Gift to the Pesticides Lobby.

Warning : This Drug May Kill You

Health experts discuss opioids and the dangerous role they play in treating pain

Told from the perspectives of four families devastated by opioid addiction, Warning: This Drug May Kill You offers a harrowing, unflinching look at the deadly epidemic currently facing the United States.

FDA’s new drug approvals : is there evidence that the public is happy to sacrifice safety for speed ?

Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort study

Most drugs today qualify for one of the FDA’s expedited pathways. But what is the evidence that the public is on board with the notion of sacrificing safety for speed?

What is already known on this topic
  • Recent legislation in America opens the possibility for the expansion and increased use of FDA expedited drug development and review pathways designed to respond to public health priorities
  • Evidence on whether drugs approved through expedited regulatory pathways carry higher levels of safety risks that are unknown at the time of approval is conflicting
  • Some studies suggest that the review process does not impact the quality of the safety assessment, whereas others show a difference
What this study adds
  • In this analysis concerning more than 15 years of comprehensive data, expedited pathway drugs had a 38% higher rate of safety related label changes than drugs approved through non-expedited pathways
  • As policymakers continue to expand expedited regulatory pathways, physicians and patients should be aware of the potential safety trade-offs involved in these pathways

2017 Study Abstract

Objective
To determine if drugs approved through the Food and Drug Administration’s expedited development and review pathways have different rates of safety related label changes after approval compared with drugs approved through standard non-expedited pathways.

Design
Retrospective cohort study.

Setting
FDA public records, January 1997 to April 2016.

Participants
382 FDA approved drugs.

Main outcome measures
The number of times a particular safety section of a label (boxed warning, contraindication, warning, precaution, or adverse reaction) was changed during a drug’s time on the market. The relative rate of safety related label changes per year for expedited pathway and non-expedited pathway drugs was compared by forming matched pairs of drugs in the same therapeutic class that were approved within three years of each other.

Results
Among the 382 eligible new drugs, 135 (35%) were associated with an expedited development or review pathway, and matches were available for 96 (71%). The matched pairs were associated with a total of 1710 safety related label changes during the study period. Expedited pathway drugs were characterized by a rate of 0.94 safety related label changes for each drug per year, compared with 0.68 safety related label changes per year for non-expedited pathway drugs (rate ratio 1.38, 95% confidence interval 1.25 to 1.52). Compared with non-expedited pathway drugs, expedited pathway drugs had a 48% higher rate of changes to boxed warnings and contraindications, the two most clinically important categories of safety warnings (1.48, 95% confidence interval 1.07 to 2.06). A qualitative review of changes to the boxed warning sections revealed that less than 5% (3/67) were changed to describe reduced risks for patients.

Conclusions
Expedited development and regulatory review pathways can accelerate the availability of new drugs, but drugs approved through these pathways are associated with increased safety related label changes after approval, particularly for the types of changes representing the highest risk warnings. To inform appropriate policy interventions, additional research should explore the causal factors contributing to these different rates.

More Information

  • Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort study, BMJ 2017;358:j3837, 07 September 2017.
  • Speed vs safety in the FDA’s new drug approvals—speed wins, again, blogs.bmj, September 12, 2017.
  • Featured image credit stickergiant.

USPSTF Draft Recommendation Statement Cervical Cancer : Screening

The US Preventive Services Task Force has New Draft Guidance for Cervical Cancer Screening

These recommendations do NOT apply to women with in utero exposure to diethylstilbestrol or women who have a compromised immune system (e.g., women living with HIV).

The major change from the US Preventive Services Task Force (USPSTF) 2012 recommendation is that testing for high-risk strains of human papillomavirus (hrHPV) alone is now recommended as an alternative to cytology or Papanicolaou (Pap) screening alone beginning at age 30 years; cotesting is no longer recommended.

As in the 2012 recommendation, the USPSTF continues to recommend that women aged 21 to 29 years undergo Pap screening every 3 years.

The USPSTF recommend against screening in women younger than age 21 years because there is adequate evidence that regardless of sexual history, screening younger women does not reduce cervical cancer incidence or mortality.

The USPSTF also continues to give a thumbs down to screening in women older than age 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer, as well as in women who have had a hysterectomy and their cervix removed and do not have a history of a high-grade precancerous lesions or cervical cancer.

More Information

EDCs : evidence that co-exposures should be considered when evaluating the risk of a single chemical

Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants

2017 Study Abstract

BACKGROUND
Numerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life.

OBJECTIVES
Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals.

METHODS
We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10–12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures.

RESULTS
We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose–response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight.

CONCLUSIONS
Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life.

Discussion

Concerns that the traditional focus of chemical risk assessment on single chemical exposures might underestimate the risks associated with adverse effects of multiple chemicals have been expressed earlier (Kortenkamp 2014), but the impact on risk estimates has been proven difficult to define. This is partly due to incomplete information about the complexity of combined human exposures and to a lack of clarity about the approaches and methods that should be used for mixture risk assessment. Our study provides important advances in improving the scientific basis for human mixture risk assessment. To our knowledge, we demonstrate for the first time that the mixture assessment concept of dose addition is applicable to human tissues. This not only enabled us to avoid certain uncertainties associated with animal-to-human extrapolations, but also enabled us to use a predictive approach. Rather than studying every conceivable combination of chemicals within a mixture, the joint effects of anti-androgenic chemicals in the FEGA can now be approximated on the basis of the effects of each single component by using dose addition as the default assumption.

To utilize the FEGA in multi-component mixture studies required making a leap from qualitative studies to quantitative dose–response analyses. Due to the inhomogeneity of the material and the variations inevitably introduced through the age differences of the fetal testes, the assay outcome (fetal testosterone production) shows high variability, which we had to deal with by rigorously controlling experimental conditions. We achieved good reproducibility, which was essential for realizing our goal of analyzing whether the combined effects of multiple chemicals can be predicted accurately on the basis of the effects of individual mixture components and of assessing the impact of co-exposures on the dose–response curves of single chemicals.

A difficulty in using the FEGA as a screening method for the identification of chemicals with endocrine disruptive properties is the limited availability of human fetal tissue. An additional challenge is in the requirement of collecting tissues of comparable age.

Our study provides direct evidence that co-exposures should be considered when evaluating the risk of a single chemical. We show that effects of a single chemical are underestimated when co-exposure to related chemicals are not considered, and that this underestimation is driven by the number, type, and potency of co-occurring chemicals. In this study, overlooking co-exposures to only seven chemicals led to an underestimation of the potency of BPA by a factor of 10. A corollary of the principles of dose addition is that co-exposure to a larger number of chemicals will drive up the extent of such underestimations if these chemicals are present at levels equipotent with the components we used in our experiments. Alternatively, replacement of some components with larger numbers of other chemicals, but at lower levels, may lead to similar underestimations. More studies using the FEGA are needed to establish these assumptions.

Based on our findings, we suggest that the impact of mixture effects on male sexual differentiation during the first trimester of pregnancy may be considerable. However, although in this study the selection of chemicals was empirically based on the results obtained in our dose–response study, analysis of individual chemicals, assessment of the extent of adverse effects in human fetuses will require more knowledge about the spectrum of chemicals capable of suppressing testosterone synthesis. Future FEGA studies will help close this knowledge gap, especially if based on companion studies that identify all of the exogenous chemicals found in maternal and fetal tissues.

Full Study
  • Featured image : predicted and observed testosterone secretion in human fetal testis by four chemical mixtures. Experimental data are shown as mean ± SEM (blue) of at least four independent experiments. Testosterone production is represented as relative to the first day of culture (D0) production and the control level, see text for more details. The mixture effects were predicted according to dose addition (DA) (thick red curve), with dashed curves the respective 95% confidence intervals (CIs) (dotted orange lines) credit ehp.
  • Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants, Environmental Health Perspectives, DOI:10.1289/EHP1014, AUGUST 2017 | VOLUME 125 | ISSUE 8. Full PDF.
Endocrine Disruptors

Reporting side effects of medicines

EU Medicines Agency‏ survey on safety of medications and reporting of adverse drug reactions

This EU Medicines Agency survey, will take approximately 5 to 10 minutes of your time to complete. It will help understand the awareness of patients/consumers and healthcare professionals regarding the need and the way they can report adverse drug reactions (side effects). The results will be analysed by the European Medicines Agency and a report containing summary information will be provided to the European Commission (DG SANTE) and will be further disseminated publicly.

EMA launches survey to assess whether patients and doctors are aware of the arrangements for reporting of side effects – European Medicines Agency, the European Union agency responsible for the evaluation and supervision of medicinesEMA_News/status/905720311445893120, 7 sept. 2017.

Antidepressant use during pregnancy and psychiatric disorders in offspring

Danish nationwide register based cohort study, 2017

What is already known on this topic

  • Several studies have linked selective serotonin reuptake inhibitor use during pregnancy to autism spectrum disorder in offspring, although results have been conflicting
  • The potential explanation for this association is that selective serotonin reuptake inhibitors cross the placental barrier and affect the development of the fetal brain
  • If this holds true, in utero exposure to selective serotonin reuptake inhibitor and other classes of antidepressants may increase risk for various psychiatric disorders besides autism spectrum disorder

What this study adds

  • Antidepressant use during pregnancy was associated with increased risk for various diagnostic groups of psychiatric disorders in offspring
  • The observed associations may be attributable to the severity of underlying maternal psychiatric disorders in combination with in utero antidepressant exposure

Study Abstract

Objective
To investigate the association between in utero exposure to antidepressants and risk of psychiatric disorders.

Design
Population based cohort study.

Setting
Danish national registers.

Participants
905 383 liveborn singletons born during 1998-2012 in Denmark and followed from birth until July 2014, death, emigration, or date of first psychiatric diagnosis, whichever came first. The children were followed for a maximum of 16.5 years and contributed 8.1×106 person years at risk.

Exposures for observational studies
Children were categorised into four groups according to maternal antidepressant use within two years before and during pregnancy: unexposed, antidepressant discontinuation (use before but not during pregnancy), antidepressant continuation (use both before and during pregnancy), and new user (use only during pregnancy).

Main outcome measure
First psychiatric diagnosis in children, defined as first day of inpatient or outpatient treatment for psychiatric disorders. Hazard ratios of psychiatric disorders were estimated using Cox regression models.

Results
Overall, psychiatric disorders were diagnosed in 32 400 children. The adjusted 15 year cumulative incidence of psychiatric disorders was 8.0% (95% confidence interval 7.9% to 8.2%) in the unexposed group, 11.5% (10.3% to 12.9%) in the antidepressant discontinuation group, 13.6% (11.3% to 16.3%) in the continuation group, and 14.5% (10.5% to 19.8%) in the new user group. The antidepressant continuation group had an increased risk of psychiatric disorders (hazard ratio 1.27, 1.17 to 1.38), compared with the discontinuation group.

Conclusions
In utero exposure to antidepressants was associated with increased risk of psychiatric disorders. The association may be attributable to the severity of underlying maternal disorders in combination with antidepressant exposure in utero. The findings suggest that focusing solely on a single psychiatric disorder among offspring in studies of in utero antidepressant exposure may be too restrictive.

  • Antidepressant use during pregnancy and psychiatric disorders in offspring: Danish nationwide register based cohort study, BMJ 2017;358:j3668, 06 September 2017.
  • Characteristics of study population according to maternal antidepressant use before and during pregnancy. Values are numbers (percentages) unless stated otherwise, featured image credit bmj.