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Digital aripiprazole or digital evergreening? A systematic review of the evidence and its dissemination in the scientific literature and in the media
Lisa Cosgrove1,
Ioana Alina Cristea2,3,
Allen F Shaughnessy4,
Barbara Mintzes5,
Florian Naudet6
1 Counseling and School Psychology, University of Massachusetts Boston, Boston, Massachusetts, USA
2 Clinical Psychology and Psychotherapy, Babes-Bolyai University, Cluj-Napoca, Romania
3 METRICS (Meta-research Innovation Center at Stanford), Stanford University, California, USA
4 Department of Family Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA
5 School of Pharmacy, Faculty of Medicine and Health, and Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
6 Univ Rennes, CHU Rennes, Inserm, CIC 1414 (Centre d'Investigation Clinique de Rennes), Rennes, France
Correspondence to Dr Lisa Cosgrove, Counseling and School Psychology, University of Massachusetts Boston, Boston, MA 02125, USA; Lisa.Cosgrove{at}umb.edu
Background In November 2017, the Food and Drug Administration (FDA) approved a version of a second-generation antipsychotic, aripiprazole, embedded with a sensor (Abilify MyCite).
Objective To systematically review the evidence supporting the FDA's approval of digital aripiprazole and how that evidence was disseminated in the scientific literature and news reports.
Study selection Prospective, double-blind, randomised controlled trials (RCTs), non-randomised and non-comparative studies were included if they focused on the use of digital aripiprazole. All scientific publications citing the trials were included if written in English. For the news reports, all languages were included if an English translation was available, and all records that were published after FDA approval were included.
Findings In the primary evidence search, no RCT comparing digital aripiprazole with a non-digital formulation, other active comparators or placebo was found. Only three non-comparative uncontrolled cohorts were found. No study provided data on remission, quality of life or any efficacy outcome. Fourteen scientific papers were identified that cited the trials and 70 news stories met the inclusion criteria. Almost 80% (11/14) of the scientific papers and three-fourths (52/70) of the news stories conveyed an unsupported impression of benefit.
Conclusions Regulatory approval for this first-ever digital drug was based on weak evidence, and there was no evidence of better adherence with the digital version of aripiprazole compared with the non-digital version. The possibilities afforded by this technology make room for a new type of evergreening (ie, patenting of older drugs with a sensor as a 'new invention'). Both the scientific literature and news reports conveyed an unsupported impression of benefit.
Trial registration number CRD42018089515.
http://dx.doi.org/10.1136/bmjebm-2019-111204
Global spending on prescription medicines in 2018 was US$1.2 trillion and is predicted to exceed US$1.5 trillion by 2023,1 and avoidable healthcare costs due to non-adherence are estimated to be billions per year.2 3 There have been a number of recent technological advances (eg, electronic adherence monitors or EAMs—devices that record when medications have been opened) to more accurately measure adherence and more quickly intervene when needed.4 5 The latest technology is the use of a digital medicine system in which a drug is combined with an ingestible sensor that can transmit a signal when the drug–device combination is exposed to gastric acid in the stomach to allow real-time information about medication ingestion. It is hoped that this tracking will increase medication adherence and in turn result in improved health outcomes and be cost-saving (ie, result in decreased healthcare costs).
In November 2017, the Food and Drug Administration (FDA) approved a version of a second-generation antipsychotic, aripiprazole, embedded with a sensor (Abilify MyCite). Because this is the first time that a regulatory body has approved such a drug–device combination, this approval sets a precedent for how technology-enhanced products will be evaluated before marketing. Thus, a critical review of the evidence supporting this approval is needed. It is also important to examine how the clinical trial evidence for approval was represented in these news stories and reports.6 Indeed, recent research has documented the presence of 'spin' (distorted interpretation of trial evidence giving a greater impression of benefit than is warranted by the data) in both the scientific literature7–9 as well as in media reports.10–12 Imbalanced and distorted healthcare reporting can generate false hope and undermine the ability of healthcare consumers to make informed choices about their healthcare.10 13 14 A UK study on 556 media reports on drug treatments found that most articles focusing on the benefits of medicines were about new drug treatments, and few of these reports made any mention of the risks or side effects of the medicines.15
Given the money spent globally on aripiprazole (over US$7 billion the year before the patent expired in 201516), the documented need for an evidence-based approach to inform prescribing for chronic conditions17 and the medicolegal issues created by the use of digital drugs, regulatory approval should be based on strong clinical trial evidence and the scientific literature and news reports should accurately represent the clinical data. Thus, we designed a study with three main aims: (1) to review the clinical trial data that were used to support the FDA's approval of Abilify MyCite; (2) to examine the presence of spin (defined more specifically below) in the published scientific literature; and (3) to examine the presence of spin in the news reports/stories.
We developed and followed a standard protocol and registered the protocol in the international prospective register of systematic reviews (PROSPERO) prior to conducting this study.
Review of clinical trials
We reviewed the data from randomised controlled trials (RCTs) that were submitted to the FDA for approval of digital aripiprazole. If these data were unavailable, we searched for non-comparative evidence of the chip's effectiveness (including in non-randomised studies).
We included studies of patients with schizophrenia or manic and mixed episodes associated with bipolar I disorder or depression (as an add-on treatment), as aripiprazole has regulatory approval for these conditions. Prospective, double-blind RCTs were eligible if they focused on the use of digital aripiprazole compared with either aripiprazole (non-digital formulation) and/or any other active comparator (any other drug approved in the USA for the same indication) and/or placebo. In addition, non-randomised and non-comparative studies were included if they focused on the use of digital aripiprazole. For studies of acute episodes to symptomatic remission and relapses or new episodes for continuation or maintenance studies, we assessed rates of remission as a primary outcome. Secondary outcomes were quality of life, score on a symptom scale (eg, Positive and Negative Syndrome Scale (PANSS) for schizophrenia, Montgomery–Åsberg Depression Rating Scale (MADRS) for depression and so on), adherence, total withdrawals, withdrawals due to adverse events, serious adverse events, total adverse events and effectiveness of the digital ingestion tracking system (indicating that the chip is working). We did not limit included studies by date or language.
To identify eligible studies, we searched PubMed/Medline, Cochrane Library and Embase, including conference abstracts. On PubMed, the keywords used were '(abilify OR Aripiprazole) AND (digital OR sensor OR sensors OR biosens* OR wearable* OR ingestible* OR pharmaco-vigilance OR pharmacovigilance OR wireless)' (search strategies in other databases are described in the online supplementary appendix). We also requested copies of unpublished studies from the US FDA and from the pharmaceutical companies Otsuka and Proteus (see online supplementary appendix 1 for a detailed description of the request sent via email and the email responses). Additionally, we searched the databases ClinicalTrials.gov and Current Controlled Trials for relevant trials. We contacted the authors of abstracts by email for further information and the study references. If no response was obtained to a first request, they were contacted a second time.
[bmjebm-2019-111204supp001.pdf]
Two researchers (IAC and FN) independently, at both the initial stage and for duplicates, screened studies for inclusion, resolving disagreements by consensus or in consultation with a third reviewer (LC). Two review authors (IAC and FN) independently extracted the data using a data extraction sheet based on the Cochrane Handbook for Systematic Reviews of Interventions guidelines,18 extracting information on study characteristics, funding, financial conflicts of interest (FCOI) during the last 3 years, use of a ghost writer and the characteristics of the journal. We planned to assess the risk of bias for RCTs using the Cochrane Collaboration's tool for assessing risk of bias19 and observational studies with a tool from the Joanna Briggs Institute.20 We planned to perform meta-analyses if trials were sufficiently similar to be combined.
Selection of citations in the scientific literature to assess for spin
To identify subsequent reporting of the initial research findings, one author (FN) searched the Web of Science to identify all publications written in English citing the trials.
Selection of news stories and press releases to assess for spin
With the assistance of a medical librarian, we searched the database NexisUni for all news stories and press releases about the approval of AbilifyMyCite (search dates: 1 January 2015 to 23 January 2018; publication type: industry trade press, web-based publications, newswires and press releases, newspapers, blogs, business opportunities, newsletters, magazines and journals, legal news, news transcripts, scientific materials, undefined, news, patent filings). The following search terms were used: (abilify OR Aripiprazole) AND (digital OR sensor OR sensors OR biosens* OR wearable* OR ingestible* OR pharmaco-vigilance OR pharmacovigilance OR wireless). All languages were included if an English translation was available, and we included all records that were published after the device was approved by the FDA (13 November 2017).
Classification of spin in the scientific literature and news stories
Congruent with previous research, we defined spin as 'a specific way of reporting, intentional or not, to highlight that the beneficial effect of the experimental treatment [digital aripiprazole] in terms of efficacy or safety is greater than that shown by the results' (ie, overstate efficacy and/or understate harm; see Yavchitz et al, 2016) (see online supplementary appendix 2 for a detailed description of how Yavchitz et al 21 22 and Haneef et al 23 24 defined and operationalised spin and how we used Haneef et al 23 24 to develop our specific questions). Two review authors independently extracted the data from the studies included. Disagreements were resolved by consensus or in consultation with a third reviewer (LC). Following Yavchitz et al 21 22 and Haneef et al 23 24 we used the questions noted below to assess the classification of spin in the scientific literature and in the news reports, modifying question 5 slightly to assess whether the authors of the scientific literature were supported by the manufacturers of the sensor (Proteus) or of aripiprazole (Otsuka).
Did the news article acknowledge that there is no evidence that monitoring is associated with increased adherence?
Did the news article acknowledge that there is scarce safety data?
Did the news article acknowledge that the digital version was not tested against an active non-digital comparator?
Did the news article give the impression of clinical benefit to patients for which there are currently no data (eg, consistent use of words/phrases such as 'big advance', 'innovation in healthcare' or unsupported claims of positive health outcomes)?
Was an expert cited and was the expert independent (ie, was not a company representative/employee)? (In our review of the scientific literature, we asked if the authors were supported by the manufacturers of the sensor (Proteus) or of aripiprazole (Otsuka).)
We used descriptive statistics for most of the data. For the features described above, numbers and percentages for qualitative outcomes were reported. Data are shared on the Open Science Framework (https://osf.io/auc9e/).
Primary evidence search (clinical trials and observational studies)
We identified 130 articles in the databases of published trials and 20 through contacts with the FDA, manufacturers and clinical trial registries. According to Otsuka and the FDA, there were no unpublished studies that were submitted to the FDA. A representative from Proteus stated that the company was not involved in any of the trials for Abilify MyCite. The medical reviews that describe all of the clinical trials supporting the FDA's approval are available at https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207202Orig1s000TOC.cfm. In summary, the FDA decision was based on two review cycles. In the first cycle, we found three open-label, single-arm studies in psychiatric patients (studies 316-13-204, 316-13-215, 316-14-220). In the second cycle (resubmission), we found an additional study in psychiatric patients (DC-001576). This study was not included in our review since it was not a clinical study but rather a 2-day 'simulated' study in which the participants did not ingest the drug but simply placed the tablets in a container to simulate ingestion.
After removing duplicates, 107 articles remained, 95 of which were excluded at the title and abstract stage. We obtained and screened the full text of the remaining 12 articles and excluded 9, mainly narrative reviews. The three studies identified in the FDA report were included and no additional study was found (figure 1).
Flow diagram of the selected clinical trials and papers citing the trials. International Standard Randomised Controlled Trials Number. FDA, Food and Drug Administration; RCT, randomised controlled trial.
We found no prospective, double-blind RCTs comparing digital aripiprazole with the non-digital formulation, other active comparators or placebo. The three included studies (one was unpublished) were non-comparative uncontrolled cohorts25 26 (see table 1 for study characteristics), involving 67 patients with schizophrenia, 49 psychiatric patients (22 with bipolar 1 disorder, 12 with major depressive disorder and 15 with schizophrenia) and 58 psychiatric patients (35 with bipolar disorder and 23 with major depressive disorder). Effects on adherence, total withdrawals, withdrawals due to adverse events, serious adverse events, total adverse events and effectiveness of the digital ingestion tracking system (indicating that the chip is working) are presented in table 1. Neither study provided data on remission, relapse or new episodes, nor on quality of life as measured on a symptom scale. An assessment of Clinical Global Impression was planned in study 316-13-204 but not reported in the FDA summary.
Published and unpublished study characteristics
Examination of spin in citing articles in the scientific literature
Of the 14 papers in the scientific literature that cited the two included studies, 71% (10/14) did not acknowledge the lack of efficacy data from clinical trials, 93% (13/14) failed to report on both the scarcity of safety data and the fact that no comparator was used in clinical trials, and 79% (10/14) gave an unsupported impression of benefit. Regarding FCOI, 57% (8/14) of the papers had at least one author with a financial tie to either Otsuka or Proteus, and in 43% (6/14) the authors were employees of either Otsuka or Proteus (see online supplementary table 2 for an overview).
Examination of spin in the news stories/reports
We identified 861 records through the systematic search and two press releases through a search of the companies' websites; 70 met the inclusion criteria (see figure 2). Of these, 57% (40/70) did not acknowledge the lack of efficacy data from RCTs, 93% (65/70) did not report on the scarcity of safety data, and no story reported on the absence of a non-digital comparator in clinical trials. Three-fourths (52/70) conveyed an impression of benefit without mentioning the lack of research to support that impression. Most of the news stories (77%, 54/70) cited an expert, and of those 39% (21/54) cited experts who had financial ties to either Otsuka or Proteus (see online supplementary table 2 for an overview).
Flow diagram of the selected news stories. PR, press releases; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Our review of the clinical trial data submitted to the FDA for the approval of Abilify MyCite reveals that the data submitted were limited to trials that simply assessed whether patients could use the product as intended. There was no evidence of superiority or non-inferiority27 compared with non-digital versions of aripiprazole, other active comparators or placebo, and scarce data on safety. In fact, in the FDA's clinical review letter, it was noted that the one simulated trial (ie, one in which the participants did not ingest the drug but simply placed the tablets in a container to simulate ingestion), performed for resubmission, 'provides no additional data regarding adherence or data regarding data transmission times. Considering these limitations, the most accurate statement regarding Abilify MyCite's capabilities is that Abilify MyCite successfully tracks ingestion of aripiprazole with embedded sensor' (emphasis added) (p11).28 As acknowledged in the FDA letter, the lack of a single comparative trial means there is no way to know whether digital aripiprazole improves treatment adherence, quality of life, psychiatric symptoms or remission. However, the risk management plan specifically asks for an 'open label, longitudinal post marketing trial' without requiring any comparison group. Given the weakness of the design and the lack of control group, no reliable postmarketing information on effectiveness will be added.
This finding adds to the concern previously noted for non-digital versions of this drug, namely the extension of its use to disorders for which there is very limited evidence of efficacy and overall utility.29 30 For example, the FDA approved non-digital aripiprazole's use in in the maintenance of bipolar disorder based on a single trial, which had many design and methodological flaws.17 The researchers expressed strong concerns that 'the uncritical acceptance of this trial may be diverting patients away from more effective treatments'.17
Patients with serious psychiatric illnesses often suffer from paranoia. An ingestible drug with a sensor brings surveillance to a new level, and the potential negative effects on this patient population merit careful consideration.31 The potential harm of the surveillance aspect of this technology to the therapeutic alliance and to patients has not been adequately assessed. Thus, it is reasonable to ask if there was a financial rather than a scientific impetus for choosing aripiprazole as the first-ever digital drug. The sales and patent status of aripiprazole are noteworthy. In 2014 aripiprazole was the best-selling drug in the USA, costing on average over US$800 for a month's supply and generating over US$7.5 billion in sales from October 2013 through September 2014.16 However, after the patent expired in the USA, sales revenues dropped to US$600 million by 2015,32 which is when Otsuka and Proteus first submitted an application for market approval for the digital version.
Drug manufacturers have developed a number of strategies to extend market monopoly after a blockbuster drug (defined as over US$1 billion in yearly revenue) goes off-patent. These are known as 'evergreening' strategies, with highly questionable benefit to patients.33–36 Evergreening involves the patenting of a slight modification (eg, subtle changes to the medicine's structure) of an existing drug as a new invention. For the manufacturer, the result is that their product is considered as a new chemical entity that qualifies for market exclusivity (ie, no generic version is available). The possibilities afforded by sensor-based technology make room for a new dimension of practice, an evergreening 2.0.37 That is, 'digital evergreening' may develop as a means whereby manufacturers can gain market exclusivity for a generically available medicine (such as aripiprazole) by combining it with a monitoring technology. The recent United Nations Development Programme's guidance on patent applications for pharmaceutical products does not address the issue of such technology.38 The present study raises concerns about digital evergreening and approving a 'novel' drug/device that may not be either as efficacious or as safe but will cost significantly more; while the generic oral version of aripiprazole costs approximately US$20 per month, Abilify MyCite costs almost US$1700 for a month's supply.39 The increased cost has significant implications for medication adherence. In 2015, it was estimated that almost 10% of adults in the USA were non-adherent due to cost of the medicine.40
Additionally, this study adds to the growing body of literature documenting the extent and effects of spin in the scientific literature and in the media reports.7 22 Indeed, the extent of spin found in the present study is likely controlled by industry; not only were authors of the published studies Otsuka employees, but the following disclosure was also made: 'Editorial assistance was provided by the medical communications company C4 MedSolutions LLC (Yardley, PA, USA), a CHC Group company', with Otsuka funding. Both studies were published in the psychiatric journal Neuropsychiatric Disease and Treatment, whose editor is described as an 'independent pharma consultant [who] advises and consults worldwide to several pharmaceutical and venture capital organizations'. The unsubstantiated positive characterisation of this digital medication is a public health issue because this is the scientific literature that will guide prescribing practices and policy initiatives, and will likely be used to inform the development of new treatment guidelines.41
Also, previous research has consistently found that journalists typically fail to address the quality of the evidence and the assessment of harm over benefit,10 42 and our study shows that after two decades this pernicious problem persists. The fact that over one-third of the experts cited in the news stories had financial ties to the manufacturers of this new product highlights the importance of decoupling commercial messages from science by identifying independent medical experts to whom science journalists and health reporters can turn.43
As Haneef et al 23 have noted, despite advances in operationalising definitions of spin, any assessment of the misrepresentation of clinical trial data or results will inevitably involve some degree of subjectivity. Therefore, although two researchers evaluated all of the assessments of spin independently, this process cannot eliminate an element of subjectivity. Our study's findings cannot provide information about how readers of both the scientific literature and the news reports were—or if they were—misled by the spin that we identified. Finally, the fact that we only studied one drug–device combination limits the generalisability of our results.
Our case study reveals that the approval of this digital drug for marketing in the USA was granted on very limited data. Both the scientific literature and the popular news reports conveyed an unsupported impression of benefit. As a result, the general public and healthcare professionals may be making medical decisions based on industry-friendly, but not necessarily scientifically accurate, information about the efficacy and safety of this new product. Also, if patients are incentivised to take the digital version (eg, by being offered lower copayments or by being offered outpatient treatment—rather than forced inpatient treatment), the line between incentivising and coercion will be blurred.31 We recommend that other regulatory bodies (eg, the European Medicines Agency) take note of the findings in the current study as well as the medicolegal issues that emerge with the use of digital drugs.
What is already known on this topic
In November 2017, the US Food and Drug Administration (FDA) approved digital aripiprazole, a version of a second-generation antipsychotic embedded with a sensor.
This first approval of a drug–device combination sets a precedent for how technology-enhanced products will be evaluated before marketing.
Evergreening is a strategy used by industry to effectively extend patent protection by making small changes to existing products, changes that have almost no added benefit to the patient.
What are the new findings
Our review of the evidence submitted to the FDA for approval of a digital version of aripiprazole shows that approval was based on weak evidence—no prospective, double-blind, randomised controlled trials comparing digital aripiprazole with non-digital formulations of aripiprazole or other active comparators or placebo were found.
This case example illustrates the ways in which sensor-based technology can facilitate a new type of evergreening (ie, patenting of older, off-patent drugs with a sensor as a new invention to regain or maintain market exclusivity).
There was clear evidence of ghost writing in the dissemination of the trial data in the scientific literature.
This finding adds to the concern about high-tech medical companies operating in a climate of 'stealth-research' (Ioannidis, 2015; Cristea et al, in press) where their products are sheltered from the scrutiny of other scientists.
How might it impact on clinical practice in the foreseeable future?
Our results suggest that the general public and healthcare professionals may be making medical decisions based on industry-friendly, but not necessarily scientifically accurate, information about the efficacy and safety of this new product.
The authors thank Rebecca Troeger, Justin M Karter and Jacqueline Hogan for their assistance in gathering and collating the news stories and for their helpful comments and feedback.
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Contributors LC conceived of the study. LC and FN developed the design. LC, FN, IAC, BM and AFS contributed to data analysis and interpretation and review of the results. All authors discussed the results and contributed to writing the manuscript. LC took the lead in writing the initial draft, and FN wrote the draft of the primary evidence search and results. All authors contributed to writing subsequent revisions of the manuscript.
Data sharing statement Data are shared on the Open Science Framework (https://osf.io/auc9e/).
Correction notice This article has been corrected since it was published Online First. Second affiliation for Ioana Alina Cristea has been corrected.
Digital medicine systems: an evergreening strategy or an advance in medication management?
Alexander C Egilman Joseph S Ross
BMJ Evidence-Based Medicine 2019; 24 203-204 Published Online First: 21 Nov 2019. doi: 10.1136/bmjebm-2019-111265


text:
Study suggests cash might not be the best way to motivate employees
A recent survey of firms in the United States revealed that 84 percent spent more than USD 90 billion annually on tangible employee rewards, such as gift cards, recreation trips, and merchandise in hopes of increasing productivity.
Updated: August 16, 2022, 17:17 IST
The findings of a new study suggest that tangible rewards motivate employees when they're easy to use, pleasurable, unexpected, and distinct from salary. The study was recently published in the journal 'Accounting, Organizations, and Society'.
"We found that there is, at best, mixed evidence regarding the motivational efficacy of tangible rewards versus cash rewards," said Adam Presslee, an associate professor at the University of Waterloo's School of Accounting and Finance. "It is somewhat puzzling why so many companies go to the trouble of tangible rewards when cash rewards also lead to motivational differences."
Presslee and his co-author, University of Wisconsin-Madison's Willie Choi, used four experiments to investigate the factors driving the preference between cash and tangible rewards. The attributes examined include ease of use of the reward (fungibility), hedonic nature of the reward (want vs. need), the novelty of the reward, and how the reward is presented.
"Rewards are constellations of attributes, and firms should focus more on the motivational effects of the attributes associated with a reward rather than the reward type itself," Presslee said. "Results confirmed that each of these attributes - individually and in combination - increases employee effort and performance."
The researchers recommend managers interested in motivating employees using tangible rewards would be best served to offer tangible rewards that incorporate these four attributes.
"If for whatever reason tangible rewards are the only tool available, our results show compelling evidence that employees are motivated by rewards that are perceived as distinct from salary," Presslee said. "Therefore, firms looking to get the most out of their reward programs should emphasise the distinctiveness of those rewards, and the attributes above are four ways firms can do that."
Tangible rewards
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National Insurance now largest single tax expense for UK's largest firms
New report from PwC suggests corporation tax take fell £2bn last year though total tax take rose £500m
Scott McCulloch
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National insurance contributions are now outstripping corporation tax payments as the largest single tax expense for the UK's largest companies according to a new survey from PwC.
PwC's annual Total Tax & Economic Impact Survey found corporation tax take from the so-called 100 Group companies - which includes FTSE100 and large independent firms - was down £2 billion on the previous year to £6 billion in total.
Almost a third (30 per cent) of the reduction was "due to the decrease in the statutory rate of corporation tax announced by Government in 2010 to attract business and investment to the UK", PwC said.
Its report also notes "most of the remainder" of the reduction in corporation take in 2013 was down to "falling profits for oil and gas companies as oil production declined in the North Sea and costs and capital investment increased".
However, a report published by rival Big Four firm Deloitte this week suggests North Sea production output actually increased by 44 per cent last year, largely as a result of significant tax breaks introduced in the 2012 Budget.
PwC said the 100 Group companies invested more than £26 billion in fixed assets and more than £5 billion on research and development last year, both of which are deductible for corporation tax purposes.
National Insurance contributions are now the largest tax expense for the companies surveyed at 27.5 per cent.
PwC said the rise in National Insurance contributions was down to the firms it surveyed having increased headcount by 1.3 per cent while also increasing wages.
The PwC survey suggests the total tax contribution from the 100 Group companies was £77.6 billion last year, up from £77.1 billion the previous year, despite the £2 billion dip in corporation tax take.
Its report states: "For every £1 of corporation tax paid, the UK's big firms now pay £2.86 in other taxes".
PwC said corporation tax receipts have been falling in the UK progressively in recent years as a result losses incurred during the financial crisis being offset against future profits and the UK government cutting the base rate of corporation tax.
The increase in tax take among the 100 Group companies was "predominantly due to higher employment taxes, VAT and excise duties" PwC said.
PwC said the 100 Group companies in its survey collectively employ more than 2.1 million people and have implemented average wage rises of 2.5 per cent .
It found the the oil and gas and banking sectors – which it said were "key industries in Scotland", remain "major contributors", responsible for nearly half of the Total Tax Contribution.
However, this figure declined on the previous year as the proportion paid by the retail, insurance and telecoms sector expanded.
David Glen, head of tax with PwC in Scotland, said: "As one of the most open economies in the world, the UK has to work hard at retaining and attracting business as a source of jobs and tax revenues.
"Measures like the lowering of the corporation tax rate and additional incentives for innovation are all about attracting more investment to the UK, and we are beginning to see signs that this is paying off."
PwC is one of the Big Four global accountancy firms and operates a significant tax advisory division advising companies on how to minimise their tax liability.
A House of Commons Committee of Public Accounts report on tax avoidance and the role of the Big Four accountancy firms, published in April 2013, said HM Revenue and Customs "appears to be fighting a battle it cannot win in tackling tax avoidance".
The committee report found the Big Four firms collectively earn £2 billion a year for their tax work in the UK and earn $25 billion a year for tax advisory work globally.
The report stated: "The four firms insisted that they no longer sell the type of very aggressive avoidance schemes that they sold ten years ago.
"While this may be the case, we believe they have simply moved to advising on other forms of tax avoidance which are profitable for their clients; such as the complex operating models they offer to major corporate clients to minimise tax by exploiting the lowest international tax rates.
"The four firms have developed internal guidelines on where the line between tax planning and aggressive avoidance lies, but these principles do not stop them selling schemes with as little as a 50 per cent chance of succeeding if challenged in court.
"Clearly HMRC has to consider the risk to the taxpayer of a protracted legal battle. It would appear that firms and tax avoiders are taking advantage of the constraints under which HMRC is obliged to operate.
"Furthermore, HMRC is always constrained by resources."
A report published by HMRC last October suggested the government is losing more than £1 in every £10 it tries to collect from companies to tax avoidance and evasion, which HMRC estimates costs the public purse £4.7 billion in lost corporation tax each year.
Of the £4.7 billion the Revenue estimates was lost in corporation tax, around £1.4 billion was linked to large companies.
However, HMRC's figures did not include so-called 'profit shifting' avoidance schemes used by multi-national companies to move tax liabilities offshore.
The HMRC report revealed the total "tax gap" between what it expects to take in revenue and what it actually collected rose to £35 billion in the 2011/12 year, up £1 billion on the previous year's estimate.
Revenue figures suggest £4 billion a year is lost through legal tax avoidance schemes, while £5.1 billion is lost as a result of illegal evasion and £4.7 billion is lost as a result of criminal activity.
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Life sciencesHe will be replaced with the current managing director of the firm's health and nutrition division
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Ferguson Marine chair and board member step down
MaritimeNationalised shipyard advertises for their replacements, plus another non-executive director
High Court dismisses 'irrational' case in boost to oil and gas firms
North Sea oilJudge disagrees with legal arguments brought by environmental campaigners
Start-upsFormer WeWork director hired by Scottish proptech start-upThe new vice president of strategy and growth is Desana's first senior hire
M&S set to close Sauchiehall Street store
Marks & SpencerThe retailer blamed 'changing shopping habits', but said it would continue to invest in 12 other Glasgow stores
EconomyMeanwhile, the average Scottish house price hit a record level of £183,000 in November
Sturgeon eases Omicron restrictions from Monday
Scottish GovernmentThe First Minister confirms changes to social distancing, indoor public events and hospitality table service
Banking industry boss defends closure of half of Scotland's branches
Banking & FinanceHe argued that it was 'uneconomic' to keep them open as demand for cash had fallen
Unite demands intervention over oil company's mandatory vaccine rule
North Sea oilPetrofac, Aker, EnerMech, Bilfinger and Global E&C are currently allowed to send staff to rigs unless they have been vaccinated
Cawood acquires Express Micro Science
Science & TechnologyWest Lothian-based EMS will now operate as a division of Cawood
Food sales shine for Scottish retailers during December
Retail & ConsumerOn a two-year basis, overall sales continued to perform well below pre-pandemic levels


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Dave Broom
Becky Paskin
Richard Woodard
Opinion & Debate
The whisky virgin
Whisky heroes
Collecting & Investing
The collectors
Legendary Bottlings
From the editors >
12 January 2016 by Dave Broom
It was one of my Perth cousins who played it to me first. Can't remember how old I was. Young, but old enough, just finding my own way in music the way you do – recommendations, sitting at people's feet, listening, plucking up the courage to say: 'I don't like it.'
Not that I disliked Abbey Road. I loved it. It intrigued; you didn't know what was coming next, how long the song would be. Some went on forever, it seemed, put you in a trance; others flashed by like thoughts.
I got a copy, my own copy, an entry point. Played it obsessively, as you do when you only have four LPs and a clutch of singles. One day I'll tell you what the rest were – I'm not embarrassed.
Abbey Road: the now iconic album cover has been replicated by thousands of fans visiting the namesake London studios.
To be honest, I've never been a Beatles obsessive. I left them behind soon after that purchase. I grind my teeth when they appear on the covers of Mojo and Uncut yet again.
'I can take them or leave them,' I say if the subject ever comes up. 'Yes, I see their genius, I know how they were groundbreakers, but they didn't have the swagger of the Stones, the wild vision of Dylan or Brian Wilson. Yes, there were great moments, but weren't The Beatles just an Irish showband wanting to please, rather than taking risks?'
Neither do I buy into the reverence afforded to Sergeant Pepper; it's always been Abbey Road for me. It's their most fully realised album, the most richly layered, the one where they worked out how to use the studio as an instrument.
It's as near to perfection as they got. If I didn't like it, then why would I go to London for an evening, and sit around drinking whisky, listening to it? I could do that at home.
I was in London because I was listening to Abbey Road… in Abbey Road.
I say that to people, I say it to my 19-year-old niece and she goes: 'I hate you.'
Abbey Road. In Abbey Road.
With Glenrothes.
The idea is, let's face it, stone cold genius. People. A room with a great hi-fi, a classic album (on vinyl), and you have a few drams.
I realise that I know all the words, the breaks, the arrangements. We mouth words and bass lines to each other, play along with Ringo. It takes me back to those nights in attic rooms and bedsits when you are finding your path in music, when you were discussing, passing on, learning. It takes me back to Perth and the memory of that beloved cousin, now gone.
Except now I'm not just in a room, I'm in the room where it was made. Those pianos were on it, that's the mike that Lennon sang into, there's the old mixing desk. I become the fanboy, grin as I shiver.
To some musicians this studio might just be a place of work, but I doubt it. This is a space that brings joy, a space that creates. There's something about this room that goes beyond acoustics, that draws from the patina of sound that's been laid down on the walls.
Some rooms just have it, in the same way as distilleries have it. There's a whisky link, but this isn't a night for connections being forced upon you. They come, they rise, you muse on them for a second, and move on. Sitting. Listening. Sipping.
Whisky and vinyl: is there a greater pairing?
That lack of agenda was what made it work. At no point were there ever attempts to draw parallels: 'The choral section in Because is like the soaring stills in the Glenrothes stillhouse; the rich bass line on Come Together is like the depth given by Sherry casks; making an NAS whisky is like George Martin mixing, or the flow of Side 2's medley; the energy of young whisky used here reflects the playfulness of Octopus' Garden.'
Many brands would have. The 'Rothes guys didn't. In this world of complicated, overthought marketing projects, that is bold.
No, this was a simple idea, perfectly executed. This album is a classic; we think these drams are a match in quality. Sit back, relax and enjoy Abbey Road.
In Abbey Road.
Sometimes in this life you are just blessed.
More From the Editors
The Glenlivet capsules: why the hysteria?
09 October 2019 What's more outrageous: cocktails served in capsules or the fact it's a Scotch? asks Becky Paskin. Read More
Scotch whisky's World Class evolution
02 October 2019 The global bartending competition has placed Scotch flavour at its heart, writes Dave Broom. Read More
A good story just adds to whisky's pleasure
25 September 2019 When whisky has a compelling tale to tell, says Richard Woodard, we should all lend an ear. Read More
From the editors 28 June 2017
Rediscovering the wonder of whisky
A centuries-old text reminds Dave Broom of the open-eyed joy that whisky once inspired.
Latest news 26 November 2018
Lindores Abbey dig unearths historic 'first'
Remains found at the Fife site could point to Scotland's earliest site of distillation yet ...
Latest news 13 December 2017
Lindores Abbey starts whisky production
The Lowland distillery at Fife's historic landmark is set to begin its first distillation.
From the editors 05 September 2018
It's time to protect whisky's history
Dave Broom argues why historical sites such as Lindores and Kennetpans must be preserved.
Latest news 12 June 2017
Lindores launches mouser-naming competition
The winning entrant will receive membership to the distillery's preservation society.


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Can I Find Out Someone's Residential Address In Merseyside?
My wife and I are no longer together and both of us are seeing new people in Kirkby, though our kids stay with my wife and grumble about how her boyfriend interacts with them.
Since I'm not present when our children stay with my wife in Liverpool, I can't tell what takes place when her new boyfriend is present.
My kids mean the world to me and ensuring they are safe in Liverpool is one of my greatest concerns.
Can I Uncover Where Someone Stays In Merseyside?
You do have a friend's contact number, though you no longer have the address and want to get their address since the contact number no longer works and you need to make contact with them in Liverpool immediately.
To locate a person in Merseyside, the team at Private Investigator Liverpool can assist you through investigating the specific person.
How Can I Uncover What A Person Is Doing In Liverpool?
You have your suspicions that one of your female neighbours in Liverpool is busy with something that is against the law.
There are countless men who visit her at various times during the day and night at her home in Liverpool.
One of your staff members at your Liverpool business is frequently absent because of illness and when he comes back to work he is exhausted.
I'm concerned that he is not doing great, though my gut is also telling me he has a second job in Merseyside.
Previous staff member from my Liverpool company is on gardening leave and could be interacting with competition or clients.
I need to determine whether or not this former staff member is adhering to the conditions of his gardening leave in Liverpool.
An investigation completed by Private Investigator Liverpool based in Liverpool into his relationship with a female rival.
How To Get Debt From A Person In Merseyside Back?
An estranged relative from Liverpool has borrowed some cash from you, now that you need the money to be repaid you cannot locate him.
He has informed a relative in Liverpool that he has relocated, however he did not share the address.


text:
require 'spec_helper'

describe ElectricSheep::Notifier do
  NotifierKlazz = Class.new do
    include ElectricSheep::Notifier
  end

  describe NotifierKlazz do
    it 'makes initialization options available' do
      notifier = subject.new(job = mock, hosts = mock, logger = mock, mock)
      notifier.logger.must_equal logger
      notifier.job.must_equal job
      notifier.hosts.must_equal hosts
    end
  end
end

redpajama_set_name: RedPajamaGithub


text:
New book 'Dokken: Into The Fire and Other Embers of 80s Metal History' available
Author James Cull is back with a new book and this time on the mighty Dokken. Cull did multiple interviews with lead vocalist Don Dokken and bassist Jeff Pilson for his book but unfortunately, guitarist George Lynch and drummer "Wild" Mick Brown declined to participate.
Amazon indicates: "In 1989, Dokken was at the peak of their musical powers and had shared the stage with bands like AC/DC, Metallica, Aerosmith, Judas Priest, Van Halen, and the Scorpions. But just as they were about to grab hold of rock 'n' roll super stardom and become full-fledged arena headliners, it all came crumbling down. Drugs, greed, and egos clashed causing the demise of one of the greatest bands to come out of the '80s. Though often maligned as an emblematic L.A. "hair metal" band, Dokken proved that they were far more than that.
With a series of multi-platinum albums like: Tooth And Nail, Under Lock And Key and Back For The Attack, Dokken helped define the "Decade of Decadence," while writing the sound track to Generation X. From personal interviews with Don Dokken and Jeff Pilson, as well as notable people from that era, this book recounts the incredible story of Don Dokken, George Lynch, Jeff Pilson, and Mick Brown. It tells of their humble beginnings before they formed Dokken, their early bands, and their struggles on L.A.'s famous Sunset Strip. This book also goes into detail about how Dokken came together, covers their rise and fall, and their reconciliation nearly twenty years later."


Jun 10, 2018· Trommel Screen, Trommel Screen Suppliers and Manufacturers at . Trommel Screen, Wholesale Various High Quality Trommel Screen Products from Global Trommel Screen Suppliers and Trommel Screen Factory,Importer,Exporter at reliable quality vibrating screen manufacturers in india. .
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We are reckoned as the prime Manufacturer, Exporter and Supplier of the highest grade Vibratory Screen in India. Our Vibratory Screen is used in diverse industries. The Vibratory Screen, offered by us, is available at the most competitive prices for the clients.
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The HDR 165 is the included headset with the RS 165 wireless headphone system. The transmitter of the RS 165 is able to feed four pairs of headphones, so additional HDR 165 headsets may be required.
Headset only. The transmitter in image not included.


Children learning Mandarin Chinese will love the bilingual world of Max and Mei. Designed for children aged 2-7 years, this best-selling children's series has thirteen storybooks, audio accompaniment, game cards and activity books.
Max and Mei go to Indonesia!
Max and Mei's new Online Home!


NWP solution, the Estonia-based company creating Intellectual healthcare ecosystem, will hold an Initial Coin Offering (ICO) for a revolutionary healthcare project. In total, the company aims to collect USD 20 million during the token sale. The NWP solution is a platform that integrates smart devices and databases into a single network that provides access to existing healthcare and quality of life services. The platform is built on advanced technologies in the field of artificial intelligence , data security and blockchain.


The main focus of my town in game will be trade, but the secondary focus is road construction, and shipbuilding.
We already have established sources for lumber, but we're currently seeking sources for paving stones.
The town name will be Byen Rhodes, the Mayors name, Mason Rhodes.
Hello, i'm your man, or Dwarf. I ll focus mining and forging. I just Beta 1 to trying it.
Qu'est ce qui a 4 pattes et un bras?
Hmm, maybe I'll form a road wrecking group, help to ensure you get a lot of repeat business.


A national charity are seeking an experienced Bid and Research Manager to join their team for a period of 9 months.
To apply for the role Bid and Research Manager, please email your CV to our Office Support team quoting the reference number 61010CH. All applicants must be eligible to work in the UK.


How I broke my phone in my Bra.
the phone became really slow and laggy.
I have this guilt feeling of purchasing things without having my phone broken.
It's a total waste to get a new phone and then I'll have an extra spare phone which I already had from before.
Anyways, it's quite stupid of me to get a new phone for this reason as well but here's how I broke it in my bra !
Of all the places I had been before with this phone, I can't believe I would have broke it in my Bra.
then i had no pockets to place my phone to jog with.
: just keep it in your sports bra.
And YES, I jogged with it.
Unfortunately, the sweat went in it and then the phone started to have dot patches and then eventually lines.
Only after a few days I concluded it got broken by my sweat.
Before that I thought it was the pressure or vibration that broke my phone.
Never jog with your phone in the sports bra.
or just be quick and dry the phone fast after that.
And there goes my idea of purchasing a new phone !


text:
Sharon Wong shares her experience working with the Hirschfield Mack collection as part of the Cultural Collections Projects Program.
As an emerging conservator, one of the most interesting aspects of the occupation is the privilege to work behind the scenes with cultural heritage collections. Arranged in alphabetical aisles with boxes of all sizes plastered with neatly printed labels and inventory identification numbers, a museum's collection store is probably one of the most organised places you would ever find yourself in. As part of the Cultural Collections Projects Program at the University of Melbourne, I was afforded the opportunity to work with the amazing and diverse range of objects housed in the maze-like permanent storage facility that is the Grainger Store.
This project involved preparing a collection of experimental wooden musical instruments that were going on loan to the Ian Potter Museum of Art (IPMA). The selection included five colour chord twelve stringed sound boxes and a colour chord twenty-one stringed flat sound box. These instruments were made by Ludwig Hirschfeld Mack who was a German artist trained at the Weimar Bauhaus School of Art and a significant contributor to art education in Australia. Sets of strings are tuned as chords and labelled with a different colour to enable the person to play by colour instead of sight reading musical notes. These instruments were mainly played in various children centres and schools in Victoria. Music samples collected from these instruments by Dr Anthony Lyons, composer and academic at the Victorian College of the Arts in preparation for the Nite Art 2017 event, also provided soothing accompaniment to the clatter of trolleys and clicking of cameras during the condition reporting process.The seamless connection between art and music further illustrates how such examples of twentieth century Australian musical culture form such an integral and fascinating part of the collections at the Grainger Museum.
Figure 1: An example of a colour chord twelve stringed sound box (left) and a colour chord twenty-one stringed flat sound box from the Hirschfeld Mack collection at the Grainger Museum (right).
As part of the loan procedures, I assessed the condition of the instruments by noting physical aspects of deterioration such as abrasions, fading, loosening of the strings etcetera. This step would help the curator to determine if an object could be safely displayed and any local treatments that may be required in order to prepare it for exhibition. The condition report would also assist with documenting the physical state of the object before it went on loan to enable a comparison to be made when the objects are returned. After the instruments have been assessed, they were securely packed in archival storage boxes for transport to the IPMA. I enjoy packing and housing collections as it involves plenty of manual dexterity and a little creativity in carving foam and wrapping archival tissue around the objects to maximise support and minimise damage during transport. Any updates to the instrument records were also entered into the EMu collection management system at the Grainger Museum to ensure completeness in documentation. These collection management and conservation activities provide an insight into the interdependent nature of various museum functions and the work involved in facilitating events such as exhibitions. The ability to be part-time sleuth, occasional historian, methodical scientist, resident accountant, amateur artisan and full time conservator also keeps me interested and challenged in this multidisciplinary profession.
Figure 2: Noting the fading of the paint and abrasions in the wood on the twelve stringed sound box (left) and fitting different pieces of foam and wrapping archival tissue around the instrument to determine the best approach towards packing the object for transport (right).
As a musical illiterate that struggles to maintain some semblance of rhythm, I have great respect for musicians and feel very privileged to be entrusted with assessing this collection. This experience has shown that music does indeed transcend boundaries and possessing such unique instruments in my primary school would have saved many music teachers from being subjected to my atrocious sight reading skills and tendency to play discordant notes. Musical abilities aside, these instruments are on their way to be displayed in The Score exhibition at the IPMA due to the assistance received from the fantastic volunteers and staff at the Grainger Museum. Further information on the objects above can be found via the Grainger Museum online catalogue.
- Sharon Wong, Cultural Collections Projects Program Volunteer


text:
Q: boosting according to user preferences in elastic search I'm currently working on a targeted ads system.
I keep track of users preferences and I'm supposed to retrieve ads accordingly.
I index ads using elasticsearch in which I index the tags of the ad:

curl -XPUT localhost:9200/ads/ad/ad789 -d '{
      "tags" : [ "sports", "gaming" ]
      }'

Now here comes the tricky part,
I want to boost the ads that have the tag sports by 8 and gaming by 2 according to the user's
preferences.

A: You can set up a function_score query with multiple filters, where each filter contributes a different boost if it matches.  For example, this query will multiply the document score by 8 if it has a "sports" tag, and by 2 if it contains a "games" tag.
{
  "query": {
    "function_score": {
      "query": {
        "match_all": {}
      },
      "functions": [
        {
          "filter": {
            "term": {
              "tags": "sports"
            }
          },
          "boost_factor": 8
        },
        {
          "filter": {
            "term": {
              "tags": "games"
            }
          },
          "boost_factor": 2
        }
      ]
    }
  }
}

By default, the boost value will be multiplied with the query score.  Alternatively, you could use the boost_mode parameter to use only the function score instead (replace), add the function score to the query score (sum), average the function score and query score (average), or use the max/min of function score or query score (max, min).
See the function_score documentation for more details.

redpajama_set_name: RedPajamaStackExchange


text:
Before the pandemic, attending events in person was just the natural order of a gathering. But a lot has changed in the last two years.…
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While safety and health are more important than ever to those looking to dust off their traveling shoes, it's clear that incentive travel has increasingly…
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The most driving question you can answer when planning an event is: Why? Why am I doing this? Why does this matter? Once your event…
5 Steps to Creating an Event Strategy
Planning an event is no easy feat. There are guest lists, vendors, venues, and seemingly hundreds of small details that are as vital to the…
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5 Hotels That Are Embracing Sustainable Practices
Sustainability is officially taking center stage. According to Deloitte's 2022 CxO Sustainability Report, almost 79% of executives see the world at a tipping point for…
7 Rules of Audience Engagement in 2022 July 28, 2022
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All Posts Attendee Engagement Downloads Event Management Event Strategy Event Trends Hybrid Events Incentive trips Insights Pharma Podcast Press Virtual Events Webinars
Apple PodcastsGoogle PodcastsAndroidStitcherby EmailRSSMore Subscribe Options


text:
Q: Sum an Array - Objective-C I'm just starting out and I'm looking for an easy way to sum a simple array. I've read into apple developer site on key value coding and I don't understand how to apply that to my array or if that's the appropriate way to sum this.
My stumbling block with the key value coding is the .keypathToProperty - I can sort of understand that you need a further reference in a 2D array but they don't show the array code, only the keypath to the title of the row so I can't figure it out yet.
NSMutableArray *numArray = [NSMutableArray arrayWithCapacity:4];
    [numArray addObject:num1];
    [numArray addObject:num2];
    [numArray addObject:num3];
    [numArray addObject:num4];

I appreciate the replies!
Thanks
Graham

A: The automatic way to do it is:
NSNumber * sum = [numArray valueForKeyPath:@"@sum.self"];

But if you're just starting out, I would recommend avoiding the collection key-path operators and go for the more simple way:
double sum = 0;
for (NSNumber * n in numArray) {
  sum += [n doubleValue];
}

A: Swift 3: (Dave DeLong's method transformed):
let sum = (numArray as AnyObject).value(forKeyPath:"@sum.self") as! Double

This should work in a similar fashion to it's Objective-C counterpart.

A: In Swift 4:
let array = [1,2,3,5]
let sum = array.reduce(0, {$0 + $1})
print(sum)


A passport valid for two months beyond the proposed duration of stay is required for British nationals.
Visas for Cuba are required by all nationals referred to in the chart above.
The required tourist visa, known as a tourist card, allows the holder to stay in the Cuba for 30 days and is valid for a single entry. You must also have a passport valid for two months beyond the length of your proposed duration of stay, as well as proof of a confirmed return flight and booked accommodation.
Nationals of the following 18 countries do not require a tourist card or a visa to visit Cuba, although the amount of time they can spend varies: Antigua and Barbuda (up to 30 days), Barbados (up to 28 days), Belarus (up to 30 days), Benin (up to 90 days), Bosnia and Herzegovina (up to 90 days), China (up to 90 days), Dominica (up to 28 days), Grenada (up to 60 days), Macedonia (up to 90 days), Malaysia (up to 90 days), Montenegro (up to 90 days), Mongolia (up to 30 days), Namibia (up to 30 days), Saint Kitts and Nevis (up to 30 days), Saint Lucia (up to 30 days), Saint Vincent and the Grenadines (up to 60 days), Serbia (up to 90 days) and Singapore (up to 30 days).
Nationals not referred to in the chart need to have a visa to visit Cuba.
Nationals of (1) the USA are subject to the Cuban assets control regulations enforced by the Office of Foreign Assets Control (OFAC; www.treasury.gov/resource-center/sanctions/Programs/pages/cuba.aspx). Travel for touristic purposes is still prohibited. That said, it's possible to visit Cuba as an American if you're visiting for one of 12 specified reasons. The permitted reasons are: family visits, official business of the US government, journalistic activities, professional research, educational activities, public performances, athletic and other competitions, humanitarian projects, exportation, importation and transmission of information. Furthermore, US nationals wishing to visit Cuba must go through authorised tour operators and groups must be accompanied by tour guides.
Tourist card: £39 (you can only apply by post and the application form is here).
The tourist card is valid for one entry of 30 days within 180 days of issue and can be extended in Cuba for a further 30 days.
Consulate (or consular section at embassy) in person or by post. Please note that in the UK, you can only apply it by post and use this official form for your tourist card. If you aren't in the UK, you can obtain application forms for tourist visa cards from certain tour operators and travel agents or from the consulate/embassy.
Allow up to four weeks for visa processing.
All visitors to Cuba are required to prove they have travel insurance covering medical expenses from approved foreign companies during their period of stay, or they will have to buy it from Cuban vendors on arrival in the country. US travel insurance policies are not accepted.
You can extend your tourist card by an additional 30 days with the immigration department.
Parents travelling with children may be required to show proof of parental rights or guardianship.
Bringing pets to Cuba is possible, but it can be time consuming and costly. You need an international (or in the case of licensed travellers from the USA, a state) veterinary certificate, completed no more than 10 days before travel to Cuba, along with proof of a rabies and distemper vaccination administrated at least 30 days before entry.
Telephone: +53 7 214 2200.
Mon-Fri 0800-1615. Due to security considerations, public access is by appointment only. Telephone: Mon-Thurs 0800-1600; Fri 0800-1300.
Mon-Thurs 0800-1630; Fri 0800-1530. Public access by appointment only. Telephone: Mon-Thurs 0900-1000 and 1400-1500.
Telephone: 020 7240 2488; 020 7420 3100.