email to Dr Claire Cope, Senior Policy Officer, Academy of Medical Sciences 3 November 2015
Please find below further evidence for the Academy’s review.
Professor Strang has consistently been subject to allegations of conflicting interests associated with his financial relationships with a number of pharmaceutical companies, most prominently with Martindale, the UK leading supplier of methadone. These conflicts are both in his professional capacity with Kings College London and South Maudsley Hospital and as an individual.
The allegations are that he does not declare fully conflicts of interest where they arise in a mandatory sense and from an ethical standpoint.
The government recently conducted a public consultation on updating the UK guidelines on Drug Misuse and Dependence.
Professor Strang is chair of the working group concerned with the consultation and update.
A full list of all those that had taken part in the consultation was published on the 30th September 2015, with the exception of two organisations and one pharmaceutical company, Martindale, (please see column 2517 at the end of the document). This was an open public consultation yet Professor Strang allowed Martindale to make its contributions in private. Professor Strang is a strong advocate for Martindale products, which include methadone, naloxone and the new buprenorphine/naloxone product, which they will bring to the market in 2016 to coincide with new updated clinical guidelines.
Professor Strang also provided written evidence to the Home Affairs Committee.
He gives inaccurate information by stating “The pharmaceutical companies have subsequently introduced and promoted a combined buprenorphine – naloxone variant (suboxone), but also you should be aware that I believe the combination product has recently been withdrawn from use in the USA following concerns about an unexpected association with deaths”.
Suboxone (buprenorphine naloxone) has to our knowledge never been withdrawn from the market, but by stating this he gave the impression that suboxone (buprenorphine naloxone) was a potentially dangerous drug. We believe there are no recorded deaths in the UK from suboxone (buprenorphine naloxone) alone.
In September 2015 Professor Strang gave a presentation in Lisbon at an international drug conference on a new formulation of buprenorphine naloxone. This is in sharp contrast to his historical views on this product but this new version that he is advocating is manufactured by Martindale, the same company that he favours and has a financial relationship with.
Professor Strang presented research about a new form of buprenorphine on Twitter @LxAddictions15 #lxaddictions15pic.twitter.com/KptTVomygm
This is a link to an article in the Independent in November 2011. http://www.independent.co.uk/news/uk/home-news/drugs-policy-advisor-under-fire-over-links-to-pharmaceutical-company-
The article covers the issue of Professor Strang’s links with Martindale, the naloxone N-Alive trials and the Medical Research Council grants. We believe that Professor Strang’s financial links with Martindale may have resulted in the N-Alive pilot being withdrawn. There was no declaration of interests on the MRC website on the N-Alive page until we submitted an FOI request and one was added soon afterwards. Professor Strang received a grant of £984.000 and upwards of £5 million for the research. http://www.ctu.mrc.ac.uk/13391/13399/18277/nalive_pi_Statement
The link below highlights a partnership between Lightlake therapeutics and Professor Strang to develop a new Naloxone nasal spray.
Professor Strang holds the intellectual property rights (patent) for the nasal application, which isn’t mentioned in this article. This needs further investigation to ensure that taxpayers’ money has not been used for this initiative. Once on the market, Professor Strang would be able to benefit financially in royalties and from selling the patent.
Professor Strang during recent years has been the strongest advocate for widening the availability of naloxone to non-medical professionals such patients/partners and family members, massively increasing the market for this drug. The premise underpinning this advocacy is that it will reduce deaths resulting from opiate overdose.
£1 million was made available from the Medical Research Council for a research project evaluating the provision of Naloxone on prison release.
Professor Strang and Kings College London were the successful applicants and Martindale was selected to provide 56,000 units of naloxone for this research. Professor Strang was criticised in the Independent article for not declaring his relationship with Martindale Pharma during the application process. Although technically within the rules, his decision at the least demonstrates poor judgement given the level of criticism he had already received about a lack of disclosure prior to this application and the subject of a complaint to the GMC and also Kings College London.
Independent article July 2011 http://www.independent.co.uk/life-style/health-and-families/health-news/professor-who-wrote-coalition-health-policy-was-paid-by-drugs-firm-2325928.html
As part of the National Naloxone Programme Scotland, naloxone kits were issued in 2013/14 and trends in opioid-related deaths. Between 2011 and 2014 there were 13,808 naloxone kits distributed, however, in this report there is not one example where naloxone has saved someone’s life.
In addition to his relationship with Martindale pharma and not covered by the media was that Professor Strang had at this time also registered a patent for a formulation of naloxone delivered nasally.
As Professor Strang holds the patent on a formulation and application of naloxone, it is surprising that he was selected to conduct the research into the viability of providing naloxone for a large non-established market.
As a patent holder, considerable benefit could have been derived from research into another formulation of naloxone, either to establish increased benefits from his own patent or avenues for additional development of his patent derived from considerable market research.
Therefore, Professor Strang has advocated a drug and delivery system, for which he holds the patent, for a market that currently doesn’t exist.
The principle of providing medication which can be administered by non-medical professionals is well established, for example, the use of an epi pen for the treatment of anaphylactic shock.
It is also well established that where medications are to be administered by non-medical professionals, the manner or ease of administration is an important factor in the success of an intervention, and therefore the selection of a particular product. For example, where medication is to be delivered by non-medical professionals, a nasal application where possible, is favoured over more invasive procedures such intravenous or subcutaneous injection.
Patent Register http://www.google.com/patents/CA2835940A1?cl=fr
What can be inferred in the above paragraphs is partly or wholly recognised by the World Health Organisation when producing their guidelines on the management of opioid overdose in the community. The WHO drew the following conclusions about Professor Strang’s fitness to contribute to those guidelines:
‘John Strang’s conflict was considered serious because his organization had received funding from Martindale, a manufacturer of naloxone, even though the funding was for work on an unrelated product, and because of his current work on a non-injectable formulation of naloxone. Both were excluded from participation in discussions and decisions relating to the use and availability of naloxone.
Professor Strang’s verbatim declaration of interest to WHO was:
‘Kings College receives £1500/month from Martindale during period of advice on a safety and pharmacokinetics PK study of a new rapid-absorption formulation of buprenorphine which has been developed by Martindale. Provides expert consultancy opinion on the trial and analysis for review of the clinical trial protocols for the trial, review of the clinical expert report on the trial and participation as an independent expert in review meetings.
£600 000 approx. to clinical trials office from Martindale for investigation of the same new formulation of buprenorphine developed by Martindale.
Organizing a new random trial in UK of a long-acting naltrexone implant versus oral naltrexone versus placebo with recently detoxified opiate addicts. Trial is fully funded by NIHR but has received implants at no cost from manufacturer and is preparing placebo implants at a modest cost. No payment has been made to Kings College, John Strang or NHS.
In early stages of studying pharmacokinetics and efficacy of possible non-injectable naloxone formulations at Kings College”
The subject matter directly poses a potential conflict of interest to anyone who owns a patent for a naloxone formulation, given previous criticisms of a failure to give a full account of potential conflicts of interest, the omission of any record of Professor Strang’s patent is surprising.
Pages 4, 5 and 67
It is of concern that the UK representative for Addiction Treatment in Europe is unable to converse on all matters due to his relationships with pharmaceutical companies, particular Martindale, and the commercial interests derived from the Patent he holds. This could be considered detrimental to the whole UK sector.
There is not, as yet, any evidence which establishes a direct causational link with the provision of naloxone and a reduction in deaths because there is no established link; the cost effectiveness of providing naloxone cannot be examined in any measure. Should the effectiveness of naloxone be established, its potential to reduce deaths may well have been considerably undermined by Professor Strang’s decision to champion it, despite such an obvious self-interest.
It is commonly accepted in the addiction sector that combating opioid overdose deaths in the community that a range of interventions is preferable. It is of note that as the thought leader, Professor Strang only appears to promote naloxone as a response to increasing opioid overdoses.
World Health Organisation 2013 discussion paper on reducing mortality from opioid overdose made the below observation in relation to utilizing alternatives to methadone:
‘The introduction and rapid medical use of buprenorphine in France in the 1990s was associated with a dramatic reduction in opioid overdose rates in that country.
It would be difficult to understand the commitment of the UK treatment system to methadone as the first and only treatment option for the vast overwhelming majority, without the knowledge of Professor Strang’s relationship with the Martindale, the manufacturer of methadone, and his dominance of the academic research field in the UK.
Despite an ever-expanding evidence base of superior interventions and detrimental impacts of long-term methadone prescribing upon the individual and particular their children and the wider community, the UK lags behinds our comparable European partners in embracing new medicines and methods which deliver superior outcomes, for example, 62% of patients treated in France are in employment against 7% in the UK. (Equator 2012)
These observations represent a small sample of what was publically available, in order to fully understand the damage which the treatment sector may have been subjected to, a full investigation into Professor Strang’s relationships with the pharmaceutical industry particularly.
I think you will agree that this is exactly what results in the public losing trust in doctors and science.
Dear Dr Cope, 5 July 2015
I have been given your email address in the reply by Hannah Hobson to my letter (below) to Professor Sir John Tooke on involuntary (iatrogenic) tranquilliser addiction.
I am pleased to have received a positive response and I, and I am sure others, will be happy to contribute to the call for evidence.
However, I do hope that this will lead to effective action. Over a thirty year period MPs, academics and victims of benzodiazepine and z drugs prescribed by their GPs have provided extensive evidence, all of which is on the website www.benzo.org.uk
More recently, evidence has been sent to the Department of Health, the MHRA, the Royal Colleges, the MRC, various professors and a host of other people and organisations responsible for health, through the APPGITA political campaign www.appgita.com
As you will have gathered from my letter, none of this has led to effective action to tackle this problem. I hope that this call for evidence will actually lead somewhere apart from yet another publication or report.
What is required is the enforcement of the 1988 CSM 2 – 4 week tranquilliser prescribing guidelines for new patients. Secondly, the creation of national dedicated tranquilliser withdrawal services based on the Ashton taper, separate from substance misuse services as the treatment requirements are different. Thirdly, proper drug regulation by the MHRA so that companies do not cause harm by withholding clinical trial data for commercial gain, for example, as Wyeth did with Ativan and GSK did with Seroxat.
On 3 July 2015 at 11:08, Policy <firstname.lastname@example.org> wrote:
Dear Mr Perrott,
Thank you very much for your email to Sir John Tooke concerning our ‘Evaluating Evidence’ project, and I apologise for the delay in responding. We have received a lot of interest in this study, and are currently considering its scope in light of the feedback we have received. Early meetings with stakeholder groups have highlighted to us that industry involvement in research, and the perception of such research by the medical community and citizens, is an important topic. We are currently considering whether this question would be best answered by the ‘Evaluating Evidence’ project, or a separate but parallel work stream. We feel the breadth of issues may be better suited to having multiple focused projects.
Thank you for the information you sent regarding the problems associated with involuntary addiction to benzodiazepine, and the long battle that patients have had to get these problems properly recognised. Clearly this is an important topic and we will carefully consider how best to incorporate it into our project, or parallel projects. We do plan to seek wider input via a call for evidence issued later in the year. Any individual or organisation (including the APPGITA, if they wish) will be able to contribute views via this route, and we will be in touch with information on how you can contribute in due course.
In the meantime, if you have any further questions, please contact Dr Claire Cope, our Senior Policy Officer (email@example.com), who will be working on the ‘Evaluating Evidence’ project over the coming year.
Dear Professor Sir John Tooke, 27 June 2015
I am writing regarding a BBC news article yesterday in which Prof Dame Sally Davies was reported as having concerns about the use of medicines damaging faith in the way research is carried out and presented, and ‘about a view that doctors and scientists are “untrustworthy”’. The article said that Prof Dame Sally Davies has written to you in your capacity as President of the Academy of Medical Sciences to request an independent review of the safety and efficacy of medicines.http://www.bbc.co.uk/news/health-33127672
I have provided research in an unpaid capacity for an All Party Parliamentary Group on Involuntary Tranquilliser Addiction (APPGITA) for the last 5 years. The APPG campaigned for patients’ rights, who through no fault of their own have become addicted to benzodiazepine and z drug tranquillisers prescribed beyond the 2 – 4 week CSM guidelines issued in 1988.
I wish to contribute to the review being conducted by the Academy of Medical Sciences with the following evidence:
After 30 years of inaction by the Department of Health to help over a million patients who have been abandoned by their GPs on these prescribed drugs (with most likely to be addicted), the All Party Parliamentary Group on Involuntary Tranquilliser Addiction was formed in 2008 and chaired by the late Jim Dobbin MP.
The work of APPGITA and the campaign is documented on this website which I manage http://www.appgita.com/
APPGITA worked hard to get the Department of Health to take effective action. In July 2009, Gillian Merron, then Public Health minister, announced that the Department of Health would conduct a policy review on addiction to medicines, including tranquillisers.
Campaigners, some of whom had been bringing this issue to successive governments’ attention for nearly thirty years, welcomed Gillian Merron’s statement. However, it was not long before it was apparent that the process was developing into a sham for the following reasons:
1. The Department of Health and the Royal Colleges continually and consistently persisted to incorrectly treat the issue as substance abuse by the patients. This continued throughout the Department of Health’s Policy review processes. In reality, patients were not warned regarding the addictive nature of benzodiazepines. One benzodiazepine widely used, Ativan, had no warnings regarding dependence from Wyeth the manufacturer receiving a licence in 1972 until 1988,by which time a benzodiazepine addict population had been created. Wyeth knew that it was addictive in 1972 through the De Buck trials yet the regulatory authority at the time took no action. Evidence has been presented to Dr June Raine, Director, Vigilance and Risk Management of Medicines at the MHRA showing that Wyeth knew about Ativan by comparing drug data sheets from different countries yet, to this day, no action has ensued. I wish to point out that there are still patients being prescribed Ativan (lorazepam) today who became addicted in the 1970s. I personally suffered a 32 year addiction to Ativan and a protracted withdrawal with no NHS support because there are no NHS tranquilliser withdrawal services. The only support available is provided by a handful of specialist charities which have been supporting those iatrogenically addicted since the 1980s.
You may read more about this here – http://www.benzo.org.uk/behan2.htm
The MHRA routinely destroys clinical trial data after 5 years making accountability of drug companies almost impossible. Not one drug company has been prosecuted for withholding data and the MHRA appears to be the first line of defence for the industry. Not one of the recommendations which would benefit patients made by the Health Select Committee’s 2004/5 report on the Influence of the Pharmaceutical Industry was implemented. The enquiry found that the MHRA is far too close to the industry and operates a revolving door system.
2. As part of its policy review, the Department of Health commissioned two reports, one from the National Addiction Centre at Kings College London, the other from the National Treatment Agency (now PHE). Professor John Strang who co-authored the National Addiction Centre (KCL) report informing the review had undeclared interests with manufacturers of the drugs which were the subject of the review, including Genus/Brittania which manufactures Ativan and Clonmel Healthcare whichmanufactures diazepam zopiclone and zolpidem.
Professor Strang also had a financial relationship with Napp Pharmaceuticals, Reckitt Benckiser all of whom manufacture codeine containing over the counter products which were also part of the subject matter of the DH policy review. These conflicts of interest were not declared by Professor Strang at tendering or publication.
Despite the fact that the NAC report was supposed to be a literature review it “missed” 129 papers documenting the harms caused by long-term use including correlation with early death; long-term use causing dementia; that 40 – 80% of users become dependent; the withdrawal syndrome being much longer than for other drugs of dependence; no mention of the post-withdrawal syndrome (PWS); that symptoms may persist for up to 5 years or more; withdrawal taking up to a year or more; social deterioration including failure in achievement and professional decline , divorce, bankruptcy; suicidal ideation, suicide attempts, suicides caused by addiction/withdrawal symptoms; depression; long-term illness being caused which is much worse than the original condition benzos prescribed for; long-term use causing agoraphobia, depersonalisation and perceptual distortions; benzo babies (floppy infant syndrome); and toxic poisoning.
None of these known harms were mentioned in the NAC report yet the scientific papers were all easily accessible from websiteshttp://www.benzo.org.uk/amisc/rpeart.pdf
Most notably Professor Ashton’s voluminous work on tranquillisers and tranquilliser withdrawal was virtually ignored. Professor Ashton is a world recognised expert on benzodiazepines and has written over 70 papers on the subject. Professor Ashton wrote a manual on benzodiazepines http://www.benzo.org.uk/manual/ which underpins the successful slow taper method of withdrawal and also ran a tranquilliser withdrawal clinic in the 1980s.
The evidence of benzodiazepine related brain damage by another benzodiazepine expert, Professor Lader, was dismissed in one sentence. http://www.benzo.org.uk/lader2.htm
The late Jim Dobbin MP wrote to the Department of Health and Andrew Lansley regarding Professor Strang’s undeclared pharmaceutical interest but no action was taken.
I have written to the authors of the NAC report asking for an explanation but they do not reply.
The report provided by the National Treatment Agency (NTA) informing the review was incorrectly on substance misuse. It contained incorrect information quoted by Earl Howe, Health spokesman in the House of Lords, more than once in Parliamentary debates, including the claim that most local areas had tranquilliser withdrawal services when a survey I conducted proved that 83% of local areas did not. Survey of PCTs in England recording provision of services for involuntary tranquilliser addiction by John Perrott
In 2014 the Department of Health figures for drug hospital admissions showed that prescription drugs dwarf those for illegal drugs with a total for heroin and cocaine combined at 4684 yet admissions for prescription drugs (benzodiazepines, z drugs and antidepressants) combined total 54,474. You would think the Department of Health would act on this yet inaction yet again prevails.
3. Further undeclared conflicts of interest in the benzo campaign included Professor Nutt. A submission was made to the ACMD in 2003 on the harms associated with benzodiazepine tranquillisers. On the advice of the ACMD Technical Committee chaired by Professor Nutt the ACMD concluded that the reclassifying and/or rescheduling of benzodiazepines would be likely to be ineffective. Professor Nutt had serious undeclared conflicts of interest at the time with benzodiazepine tranquilliser manufacturers, including Wyeth which manufactures Ativan. You may read more about this hereOmand Review of the ACMD
Professor Nutt has been a strong advocate of the use of drugs including benzodiazepines and antidepressants. He has financial links with many drug companies which he often does not declare. The credibility of the 2003 government inquiry into anti-depressant drugs on which he sat was questionable with most of the inquiry members, including Professor Nutt, having shareholdings or other links to the manufacturers. GSK’s Seroxat was known to cause suicidal behaviour amongst other ADRs. Professor Nutt and Professor David Baldwin, who also has many pharmaceutical interests, jointly fronted the promotional press launch of Seroxat.
I also point out that the half-dozen tranquilliser withdrawal charities, including BDTP http://www.btpinfo.org.uk/ and CITAhttp://www.citawithdrawal.org.uk/ report that antidepressants now outnumber benzodiazepines in calls from patients needing help withdrawing from psychiatric medication.
I have reported both Professor Strang and Professor Nutt to the GMC but the GMC does not understand what a conflict of interest is or that it includes a bias or a perception of bias and does not necessarily mean a direct financial reward to either the professor concerned or the drug companies involved. I also reported Professor Strang to Kings College London which conducted a whitewash inquiry and found him not guilty. It is impossible as a damaged patient to challenge powerful institutions or for that matter government bodies and exact any fairness as they are all self-serving and protect themselves.
4. Doctors continue to ignore the 1988 CSM 2 – 4 week prescribing guidelines which remain unenforced after 27 years of non-compliance which caused the problem in the first place.Patients we are in contact with verify this and prescriptions for tranquillisers have remained at around 16 million for a decade.
What is the point of guidelines if doctors ignore them?
Many doctors do not understand ADRs because they do not receive training in pharmacology.
Patients are left on medication, especially psychiatric medication, for years with no review. Adverse drug reactions are mis-diagnosed as new symptoms leading to polypharmacy, patients are withdrawn too rapidly and withdrawal symptoms are often mis-diagnosed.
All of these issues have been reported through voluminous correspondence with the Department of Health, PHE, the Care Quality Commission, the Royal Colleges and numerous other agencies and organisations over nearly three decades and still no effective action has been taken.
My MP, Eric Ollerenshaw, a member of APPGITA, requested a meeting with Prof Dame Sally Davies on the issue of involuntary tranquilliser addiction in July last year but her office informed him that she was too busy to meet him.
I suggest you look at the APPGITA website post 25 years of “taking it seriously” by the Department of Health – a trail of false promises
It is no wonder that patients are mistrustful. The various comments by Department of Health officials and ministers are typical of the formulaic responses, pretending to care, and obfuscation received in correspondence over the years.
Prof Dame Sally Davies says that “I have, therefore, reluctantly come to the conclusion that we do need an authoritative independent report looking at how society should judge the safety and efficacy of drugs as an intervention”.
The CQC is supposed to protect patients and I appreciate they are under pressure. Professor Steve Field who is Chief Inspector knows all about this issue through correspondence with me and a meeting with the late Jim Dobbin MP. He was also past Chair of the RCGP and is aware of the addictive nature of benzodiazepines and the ordeal patients undergo to get off them. Yet, the CQC has taken no effective action on this issue despite promises to do so. Perhaps it is just too big and the CQC, like successive governments, does not know how to tackle it.
This issue is not confined to statins or clot-busting treatment for strokes. The health and care system is rotten at the core and has been for decades. It is pharmaceutically led with scant regard for patient safety. When patients are damaged by prescribed drugs all the organisations responsible for health join ranks and obstruct those damaged who ask for fairness and help.
Any enquiry must include the Department of Health, for which Prof Dame Sally Davies is Chief Medical Officer, and all the other organisations responsible for health, because the problem is systemic.
I and all the other patients I am in contact with look forward to hearing from you.
Professor Dame Sally Davies, Chief Medical Officer, Department of Health
Sir Richard Thompson, Former President, Royal College of Surgeons
Professor Steve Field, Chief Inspector, CQC