Wednesday, October 4, 2017

Most cancer drugs entered the market without evidence of benefit on survival or quality of life

Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13. BMJ 2017; 359 doi:


Objective: To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe.

Design: Retrospective cohort study.

Setting: Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013.

Main outcome measures: Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs.

Results: From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years’ follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%).

Conclusions: This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.

My commentary: My thesis of why this came to pass is that our desperation for cancer death is so great that a few months of life and the hope of maybe, perhaps, having the cure in your hands, are enough to make us suffer those treatments and for doctors to try them

Democrat veterans suffer more PTSD than Republicans -- Political Affiliation, Probable PTSD, and Symptoms of Depression in Veterans

Political Affiliation, Probable PTSD, and Symptoms of Depression in Iraq and Afghanistan Combat Veterans: A Pilot Study. Lating, Jeffrey M. et al. Journal of Nervous & Mental Disease: October 2017 - Volume 205 - Issue 10 - p 809–811. doi: 10.1097/NMD.0000000000000715

Abstract: Ideological commitment of military personnel has been associated with mitigating trauma and protecting mental health. This pilot study assessed whether Democratic and Republican political affiliation differentially predicted probable posttraumatic stress disorder (PTSD) and symptoms of depression in 62 male Iraq and Afghanistan combat veterans. The Liberalism-Conservatism Scale, the PTSD Checklist-Military Version (PCL-M), and the Patient Health Questionnaire–9 (PHQ-9) were assessment measures. Results revealed that Democratic combat veterans had stronger liberal attitudes than Republican combat veterans (r = 0.95). Moreover, of the 50% of the entire sample higher than the cutoff score of 50 on the PCL-M, 84.8% were Democrats compared with 10.3% of Republicans. On the PHQ-9, 46.9% of Democrats compared with 3.7% of Republicans were higher than the cutoff score of 20. These initial results suggest possible mechanisms of action, including differences in shattered world view assumptions, willingness to disclose emotional concerns, and physiological reactions between Democratic and Republican combat veterans.

My commentary: It is just a pilot study, so we don't know how representative is. They say that Democrat veterans suffer more PTSD than Republicans. Explanations are: "The large effects sizes found in these data suggest the possibility worth exploring further that identified political affiliation might capture a shattered world view occurring more in Democrat than Republican combat veterans. Moreover, because Republicans are more likely than Democrats to report being in better mental health (Newport, 2007), it is possible that Democrats are more likely than Republicans to disclose emotional concerns, and thus more likely to complete these types of studies. In addition, there are data to suggest that there might be basic structural differences in the brains of those who identify as conservative or liberal (Oxley et al., 2008). Therefore, it might be worth investigating if these possible differences are related to the physiological diatheses associated with PTSD and depression (Elbejjani et al., 2015; Pitman et al., 2012)."

Searching for Moral Dumbfounding: Identifying Measurable Indicators

McHugh, C., McGann, M., Igou, E. R., & Kinsella, E. L. (2017). Searching for Moral Dumbfounding: Identifying Measurable Indicators of Moral Dumbfounding. Collabra: Psychology, 3(1), 23. DOI:

Abstract: Moral dumbfounding is defined as maintaining a moral judgement, without supporting reasons. The most cited demonstration of dumbfounding does not identify a specific measure of dumbfounding and has not been published in peer-review form, or directly replicated. Despite limited empirical examination, dumbfounding has been widely discussed in moral psychology. The present research examines the reliability with which dumbfounding can be elicited, and aims to identify measureable indicators of dumbfounding. Study 1 aimed at establishing the effect that is reported in the literature. Participants read four scenarios and judged the actions described. An Interviewer challenged participants’ stated reasons for judgements. Dumbfounding was evoked, as measured by two indicators, admissions of not having reasons (17%), unsupported declarations (9%) with differences between scenarios. Study 2 measured dumbfounding as the selecting of an unsupported declaration as part of a computerised task. We observed high rates of dumbfounding across all scenarios. Studies 3a (college sample) and 3b (MTurk sample), addressing limitations in Study 2, replaced the unsupported declaration with an admission of having no reason, and included open-ended responses that were coded for unsupported declarations. As predicted, lower rates of dumbfounding were observed (3a 20%; 3b 16%; or 3a 32%; 3b 24% including unsupported declarations in open-ended responses). Two measures provided evidence for dumbfounding across three studies; rates varied with task type (interview/computer task), and with the particular measure being employed (admissions of not having reasons/unsupported declarations). Possible cognitive processes underlying dumbfounding and limitations of methodologies used are discussed as a means to account for this variability.

Keywords: Morality,  Dumbfounding,  Judgement,  Intuitions,  Reasoning

Are the Neural Correlates of Consciousness in the Front or in the Back of the Cerebral Cortex? Clinical and Neuroimaging Evidence

Are the Neural Correlates of Consciousness in the Front or in the Back of the Cerebral Cortex? Clinical and Neuroimaging Evidence. Melanie Boly, Marcello Massimini, Naotsugu Tsuchiya, Bradley R. Postle, Christof Koch and Giulio Tononi. Journal of Neuroscience Oct 04 2017, 37 (40) 9603-9613; DOI:

Abstract: The role of the frontal cortex in consciousness remains a matter of debate. In this Perspective, we will critically review the clinical and neuroimaging evidence for the involvement of the front versus the back of the cortex in specifying conscious contents and discuss promising research avenues.

My commentary: Seems to be in the back.

The Effect of an Interruption on Risk Decisions -- Interruptions decrease the novelty of the risk decision and increases its taking

The Effect of an Interruption on Risk Decisions. Daniella Kupor, Wendy Liu and On Amir. Journal of Consumer Research,  ucx092,

Abstract: Interruptions during consumer decision making are ubiquitous. In seven studies, we examine the consequences of a brief interruption during a financial risk decision. We identify a fundamental feature inherent in an interruption's temporal structure - a repeat exposure to the decision stimuli - and find that this re-exposure reduces decision stimuli's subjective novelty. This reduced novelty in turn reduces decision makers' apprehension and increases the amount of risk that they take in a wide range of financial risky decision contexts. Consistent with our theoretical framework, this interruption effect disappears when a stimulus's subjective novelty is restored after an interruption. We further find that these consequences are unique to interruptions and do not result from other interventions (e.g., time pressure and elongated thinking); this is because an interruption's unique temporal structure (which results in a repeat exposure to the decision stimuli) underlies its consequences. Our findings shed light on how and when interruptions during decision making can influence risk taking.

Keywords: risk taking, decision making, interruption

Delegating Decisions: Recruiting Others to Make Choices We Might Regret

Delegating Decisions: Recruiting Others to Make Choices We Might Regret. Mary Steffel and Elanor Williams. Journal of Consumer Research, ucx080.

Abstract: Consumers typically prefer freedom of choice, but when faced with a choice they might regret, they may prefer freedom from choice. Eight experiments show that people delegate difficult decisions, regardless of the decision's importance, and regardless of their potential surrogate's expertise. Delegation stems from a desire to avoid responsibility for potentially making the wrong choice rather than simply the desire to avoid the possibility of a poor outcome: although anticipated disappointment with the outcome and anticipated regret about one's decision both contribute to the decision to delegate, only anticipated regret directly leads people to delegate choices to others. Consequently, delegation is an appealing method for coping with difficult choices while allowing consumers to retain the benefits of choosing that they would forgo by opting out of the choice. Moreover, giving people the option to delegate makes them less prone to walk away from difficult choices empty-handed.

Keywords: choice delegation, choice deferral, responsibility, regret

Poor Metacognitive Awareness of Belief Change

Poor Metacognitive Awareness of Belief Change. Michael Wolfe and Todd Williams. The Quarterly Journal of Experimental Psychology,

Abstract: When people change beliefs as a result of reading a text, are they aware of these changes? This question was examined for beliefs about spanking as an effective means of discipline. In two experiments, subjects reported beliefs about spanking effectiveness during a prescreening session. In a subsequent experimental session, subjects read a one-sided text that advocated a belief consistent or inconsistent position on the topic. After reading, subjects reported their current beliefs and attempted to recollect their initial beliefs. Subjects reading a belief inconsistent text were more likely to change their beliefs than those who read a belief consistent text. Recollections of initial beliefs tended to be biased in the direction of subjects' current beliefs. In addition, the relationship between the belief consistency of the text read and accuracy of belief recollections was mediated by belief change. This belief memory bias was independent of on-line text processing and comprehension measures, and indicates poor metacognitive awareness of belief change.

Keywords: Beliefs, Belief change, Metacognition, Comprehension, Recollection

Check also: Political partisans disagreed about the importance of conditional probabilities; highly numerate partisans were more polarized than less numerate partisans

It depends: Partisan evaluation of conditional probability importance. Leaf Van Boven et al. Cognition, Mar 2 2019,

And: Biased Policy Professionals. Sheheryar Banuri, Stefan Dercon, and Varun Gauri. World Bank Policy Research Working Paper 8113.

And: Dispelling the Myth: Training in Education or Neuroscience Decreases but Does Not Eliminate Beliefs in Neuromyths. Kelly Macdonald et al. Frontiers in Psychology, Aug 10 2017.

And: Wisdom and how to cultivate it: Review of emerging evidence for a constructivist model of wise thinking. Igor Grossmann. European Psychologist, in press. Pre-print:

And: Individuals with greater science literacy and education have more polarized beliefs on controversial science topics. Caitlin Drummond and Baruch Fischhoff. Proceedings of the National Academy of Sciences, vol. 114 no. 36, pp 9587–9592,

And: Expert ability can actually impair the accuracy of expert perception when judging others' performance: Adaptation and fallibility in experts' judgments of novice performers. By Larson, J. S., & Billeter, D. M. (2017). Journal of Experimental Psychology: Learning, Memory, and Cognition, 43(2), 271–288.

And: Collective Intelligence for Clinical Diagnosis—Are 2 (or 3) Heads Better Than 1? Stephan D. Fihn. JAMA Network Open. 2019;2(3):e191071,

And Poor Metacognitive Awareness of Belief Change. Michael Wolfe and Todd Williams. The Quarterly Journal of Experimental Psychology, Oct 2017.

Intergenerational Consequences of a Geographic Mobility Shock

The Gift of Moving: Intergenerational Consequences of a Mobility Shock. Emi Nakamura, Jósef Sigurdsson, and Jón Steinsson. NBER Working Paper No. 22392.

We exploit a volcanic “experiment" to study the costs and benefits of geographic mobility. We show that moving costs (broadly defined) are very large and labor therefore does not flow to locations where it earns the highest returns. In our experiment, a third of the houses in a town were covered by lava. People living in these houses where much more likely to move away permanently. For those younger than 25 years old who were induced to move, the “lava shock” dramatically raised lifetime earnings and education. Yet, the benefits of moving were very unequally distributed within the family: Those older than 25 (the parents) were made slightly worse off by the shock. The large gains from moving for the young are surprising in light of the fact that the town affected by our volcanic experiment was (and is) a relatively high income town. We interpret our findings as evidence of the importance of comparative advantage: the gains to moving may be very large for those badly matched to the location they happened to be born in, even if differences in average income are small.

Gossip as an Intrasexual Competition Strategy: Sex Differences in Gossip Frequency, Content, and Attitudes

Gossip as an Intrasexual Competition Strategy: Sex Differences in Gossip Frequency, Content, and Attitudes. Adam C. Davis. Evolutionary Psychological Science,

Abstract: From an evolutionary perspective, gossip has been considered a putative intrasexual competition strategy that is used to vie for mates and resources linked to reproductive success. To date, no study has directly examined the relations between intrasexual competitiveness, reported tendency to gossip, and attitudes toward gossiping. Limited empirical work has also focused on whether gossip frequency, gossip content, and gossip attitudes correspond to women’s and men’s divergent intrasexual competition strategies and evolved mating preferences. In a sample of 290 heterosexual young adults, we found that intrasexual competition positively predicted reported gossip frequency and favorable attitudes toward gossiping. Additionally, women reported a greater tendency to gossip in comparison to men, particularly about physical appearance and social information, whereas men reported gossiping more about achievement. Women also reported greater enjoyment of, and perceived more value in, gossiping than men. Collectively, these findings provide empirical support for the hypothesis that gossip is an intrasexual competition tactic that, by and large, corresponds to women’s and men’s evolved mate preferences and differential mate competition strategies.

Check also: What Shall We Talk about in Farsi? Content of Everyday Conversations in Iran. Mahdi Dahmardeh, R. I. M. Dunbar. Human Nature, Pay attention to the table there.

The Wisdom in Virtue: Pursuit of Virtue Predicts Wise Reasoning About Personal Conflicts

The Wisdom in Virtue: Pursuit of Virtue Predicts Wise Reasoning About Personal Conflicts. Alex C. Huynh et al. Psychological Science,

Abstract: Most people can reason relatively wisely about others’ social conflicts, but often struggle to do so about their own (i.e., Solomon’s paradox). We suggest that true wisdom should involve the ability to reason wisely about both others’ and one’s own social conflicts, and we investigated the pursuit of virtue as a construct that predicts this broader capacity for wisdom. Results across two studies support prior findings regarding Solomon’s paradox: Participants (N = 623) more strongly endorsed wise-reasoning strategies (e.g., intellectual humility, adopting an outsider’s perspective) for resolving other people’s social conflicts than for resolving their own. The pursuit of virtue (e.g., pursuing personal ideals and contributing to other people) moderated this effect of conflict type. In both studies, greater endorsement of the pursuit of virtue was associated with greater endorsement of wise-reasoning strategies for one’s own personal conflicts; as a result, participants who highly endorsed the pursuit of virtue endorsed wise-reasoning strategies at similar levels for resolving their own social conflicts and resolving other people’s social conflicts. Implications of these results and underlying mechanisms are explored and discussed.

Check also: Wisdom and how to cultivate it: Review of emerging evidence for a constructivist model of wise thinking. Igor Grossmann. European Psychologist, in press.

Brain Activity Unique to Orgasm in Women: An fMRI Analysis

Brain Activity Unique to Orgasm in Women: An fMRI Analysis. Nan J. Wise, Eleni Frangos, and Barry R. Komisaruk. The Journal of Sexual Medicine,


Background: Although the literature on imaging of regional brain activity during sexual arousal in women and men is extensive and largely consistent, that on orgasm is relatively limited and variable, owing in part to the methodologic challenges posed by variability in latency to orgasm in participants and head movement.

Aim: To compare brain activity at orgasm (self- and partner-induced) with that at the onset of genital stimulation, immediately before the onset of orgasm, and immediately after the cessation of orgasm and to upgrade the methodology for obtaining and analyzing functional magnetic resonance imaging (fMRI) findings.

Methods: Using fMRI, we sampled equivalent time points across female participants’ variable durations of stimulation and orgasm in response to self- and partner-induced clitoral stimulation. The first 20-second epoch of orgasm was contrasted with the 20-second epochs at the beginning of stimulation and immediately before and after orgasm. Separate analyses were conducted for whole-brain and brainstem regions of interest. For a finer-grained analysis of the peri-orgasm phase, we conducted a time-course analysis on regions of interest. Head movement was minimized to a mean less than 1.3 mm using a custom-fitted thermoplastic whole-head and neck brace stabilizer.

Outcomes: Ten women experienced orgasm elicited by self- and partner-induced genital stimulation in a Siemens 3-T Trio fMRI scanner.

Results: Brain activity gradually increased leading up to orgasm, peaked at orgasm, and then decreased. We found no evidence of deactivation of brain regions leading up to or during orgasm. The activated brain regions included sensory, motor, reward, frontal cortical, and brainstem regions (eg, nucleus accumbens, insula, anterior cingulate cortex, orbitofrontal cortex, operculum, right angular gyrus, paracentral lobule, cerebellum, hippocampus, amygdala, hypothalamus, ventral tegmental area, and dorsal raphe).

Clinical Translation: Insight gained from the present findings could provide guidance toward a rational basis for treatment of orgasmic disorders, including anorgasmia.

Strengths and Limitations: This is evidently the first fMRI study of orgasm elicited by self- and partner-induced genital stimulation in women. Methodologic solutions to the technical issues posed by excessive head movement and variable latencies to orgasm were successfully applied in the present study, enabling identification of brain regions involved in orgasm. Limitations include the small sample (N = 10), which combined self- and partner-induced stimulation datasets for analysis and which qualify the generalization of our conclusions.

Conclusion: Extensive cortical, subcortical, and brainstem regions reach peak levels of activity at orgasm.

Key Words: Human Female; Orgasm; Functional Magnetic Resonance Imaging; Sexual Behavior; Sexual Arousal