Month: November 2018

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PAIN CONTROL : DON’T PREGABALIN PATENT LITIGATIONS RAISE LICENSING POLICY QUESTIONS?

The painstaking way (pun intended) that “a doctor, a pharmacist, and a patent attorney” [1] have analysed the 2013 to 2018 “on going disputes around pregabalin” (British Medical Journal June 9 2018, page 358) needs commendation. I don’t comment on particular details because “Supreme Court decision is due soon” [1], but pertinent questions need answers. This excellent account implies how powerful Drug Licensing Authorities are. It is only after drugs have been licensed that MHRA, NHS, NICE, or BNF issue instructions.  Can we identify the composition of Licensing Bodies so we may hold persons to account individually when undesirable sequelae follow their decision to license a particular drug?

Adverse Clinical Consequences Following Licensing One Drug and Not Another    

I realised over 20 years ago the power Drug Licensing had in the UK when I began pointing out that Morphine and Diamorphine, through respiratory suppression, killed sickle cell disease patients in painful crises.  “If the patient dies” I said in Lancet “sickle cell crisis and chest syndrome will be recorded on the death certificate” [2 3]. When a UK Professor of Obstetrics & Gynaecology [4] advocated Morphine for sickle cell crisis patients in pregnancy, I said in BMJ: “The question that puzzles me is: Why do west African and West Indian patients with sickle cell disease who did without morphine in their countries have to be given morphine pumps during sickle cell crises when they come to the United Kingdom? In any case, in obstetrics what happens to foetal respiration when morphine is used?” [5]

Professor Elisabeth Goodman [6] found Ketorolac as good as Morphine with no   respiratory depression in vaso-occlusive crisis but Liesner, Vandenberghe and Sally Davies said “Ketorolac has no product licence in the UK for this indication” [7]

How extraordinary that a drug that did not kill patients had no Product Licence in the UK, but Morphine and Diamorphine that killed sickle cell disease patients as NCEPOD later confirmed [8] was, and still is, licensed “for this indication”! Indeed, despite NCEPOD’s damning patients-dying-from-Opiate-Overdose Report NICE issued Guidelines advocating Diamorphine intravenously in sickle cell crisis [9].

Cecilia Shoetan’s heart-rending BMJ report of her breathless 32-year-old sickle cell disease daughter dying within seconds when Diamorphine (licensed for this indication) was given intravenously in a London hospital while she stood watching [10] makes frightening nonsense of the NICE Guidance [11].

NHS ENGLAND and NHS SCOTLAND differ on Pregabalin?

The July 2007 Scottish Medicines Consortium (SMC) advice regarding Pregabalin differs from its April 2009 directive [12]. Meanwhile, NHS England had her own rules.  Witness the extraordinary situation in which NHS instructed doctors to depart from their usual prescribing for pain [13 14]. Who best should instruct doctors on prescribing practice? When Dr Margaret McCartney asked “Why do we have to prescribe branded Lyrica for pain?” [15] whom was she addressing? Well may Dr Laurence Leaver ask “With friends like NHS England, GP’s do not need enemies” [16].

Just 9 months ago we read “UK government to reclassify pregabalin and gabapentin after rise in deaths” [17]. Such reclassification is a forensic exercise. Disobey instructions and the Law could be after you. Can Freedom of Information identify individuals using “MHRA” or “NHS” or “The government” or “NICE” as cover to issue “not fit for purpose” guidelines? [18] Please investigate MHRA etc Competing Interest Declarations [19]. Pharmacovigilance in a developing country like Ghana has as many as 6 levels of vigilance and each level has potential for corruption [20]. Developed countries are no better, as Dr James Le Fanu exposes in his remarkable book recommended below.

The Le Fanu Legacy for Thoroughness

The name “Le Fanu” is music to Ghanaian ears. Korle Bu Hospital was planned and designed by Dr C V Le Fanu in the early 1910s in Colonial Gold Coast [21]. The outstanding Governor Sir Gordon Guggisberg [22] in 1919 “gave it top priority in his government’s building programme” [21] and when he opened it on 26 October 1923 he wanted it to “acquire a reputation second to none in the medical world”. One of the remarkable members of staff was another Le Fanu, Dr G E H Le Fanu who in 1909 led his laboratory in carrying out “a successful experiment to manufacture active vaccine lymph, locally, for small pox vaccination” [21]. Gold Coast Hospital, renamed Korle Bu Hospital, went on to do exploits including Dr Hideyo Noguchi’s Yellow Fever work. [21]. Meanwhile Dr G E H Le Fanu and colleagues including Dr Albert Hawe continued to tackle Tropical Diseases in a most thorough way [21 23]. Today, a Third “Thorough Le Fanu,” James, whose masterpiece “TOO MANY PILLS” is a ‘Must Read’ for every doctor mentions eight Big-Pharma companies that were fined a total of $Billion10.813 Dollars “for corrupt and illegal practices 2007-2012”. [24, page 25]

PAIN and OPIATES in HOSPITAL DEATHS

“Hospital drugs left 456 patients dead” was Daily Telegraph’s front-page head-line Thursday June 21 [25] plus an Editorial description of “fatal doses of diamorphine and other inappropriate drugs” in Gosport War Memorial Hospital. Note that when the NCEPOD Report of 2008 revealed that between January 2005 to December 2006 “Nine out of the 19 patients with sickle cell disease who had pain on admission and who then died had been given excessive doses of Opiods” [9] there were neither front-page newspaper-headlines nor calls for prosecutions as we hear today about Gosport.

Why the difference? ANSWER: Not because the victims were black, but because Morphine and Diamorphine are LICENCED “for sickle cell crisis indication” in the UK, raising this question:  Does the whole area of Drug Licensing (Pregabalin included) not need looking into urgently?  And when Dr James Le Fanu publishes in the BMJ that “Mass medicalisation is an iatrogenic calamity” [26] do we not wake up to the fact that the very first rung of the ladder to any medicalisation is DRUG LICENSING?

Finally: “Diamorphine has no accepted medical use in the United States” [27]

Competing Interest: I come from a sickle cell disease home: My Trait Parents had 11 children – 3 of us had sickle cell disease, hence my never-ceasing opposition to patient-management of pain that shortens life in anybody. [2 3 5 7 11 28 – 36].

felix@konotey-ahulu.com              Twitter@profkonoteyahul

Felix I D Konotey-Ahulu FGA MB BS MD(Lond) DSc(UCC) FRCP(Lond) FRCP(Glasg) DTMH(L’pool) FGCP FWACP FTWAS ORDER OF THE VOLTA (OFFICER) Kwegyir Aggrey Distinguished Professor of Human Genetics University of Cape Coast, Ghana; Former Consultant Physician Genetic Counsellor in Sickle Cell and Other Haemoglobinopathies Korle Bu Teaching Hospital & Director Ghana Institute of Clinical Genetics, and 9 Harley Street, Phoenix Hospital Group, London W1G 9AL.

www.sicklecell.md

1 Smyth Darren, Goldacre Ben, Croker Richard. Pregabalin: what the patent litigation means for doctors and big pharma. BMJ 2018;361:k2318 https://www.bmj.com/content/361/bmj.k2318.full?   BMJ June 09 2018

2 Konotey-Ahulu FID. Opiates for sickle-cell crisis? Lancet 1998; 351: 1438.
[“The question that puzzles me is: Why do west African and West Indian patients with sickle-cell disease who did without morphine in their countries have to be given morphine pumps during sickle-cell crises when they come to the UK?”]

3 Konotey-Ahulu FID. Opiates for sickle-cell crisis. Lancet 1998; 352: 651-652. [To David Bevan’s criticism (Lancet 1998; 351: p 1965) of white physicians who agree with Dr Konotey-Ahulu that opiates created addicts in hospital – “When I say routine opiates for sickle crisis are not the way to bring out these patients’ best potential in the long term I am glad to hear white physicians say the same…White physicians who, at the risk of being misunderstood by Bevan, voice their displeasure at what they see happening on their wards deserve commendation, not condemnation.”]

4 Chamberlain G. Medical problems in pregnancy: II. BMJ 1991; 302: 1327-30. (1 June)

5 Konotey-Ahulu, FID. Morphine for painful crises in sickle cell disease. BMJ 1991, 302(6792): 1604. (June 29 1991) (Comment on Professor Chamberlain’s recommendation of morphine in pregnancy in sickle cell disease – BMJ 1991; 302: 1327-30.) doi:10.1136/bmj.302.6792.1604-c

http://www.bmj.com/cgi/reprint/302/6792/1604-c.pdf

6 Goodman Elisabeth. Use of ketorolac in sickle cell disease and vaso-occlusive crisis. Lancet 1991; 338: 641-642.

7 Liesner RJ, Vandenberghe EA, Davies Sally C. Analgeisics in sickle cell disease disease. Lancet 1993; 3411: 188.

8 NCEPOD (National Confidential Enquiry into Patient Outcome and Death). Sickle: A Sickle Crisis? (2008) [Sebastian Lucas (Clinical Coordinator), David Mason (Clinical Coordinator), M Mason (Chief Executive), D Weyman (Researcher), Tom Treasurer (Chairman) info@incepod.org

9 NICE. Management of an acute painful sickle cell episode in hospital: summary of NICE guidance. BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e4063 (Published 27 June 2012) BMJ 2012;344:e4063

10 Shoetan Cecilia. I lost my Sickle Cell disease adult daughter minutes after being given Diamotrphine intravenously when she could not breathe. BMJ Rapid Response 3 June 2008 http://www.bmj.com/cgi/eletters/336/7654/1152-a#196520

11 Konotey-Ahulu FID. Poor care for sickle cell disease patients: This wake-up call is overdue BMJ Rapid Response May 28 2008 BMJ 2008; 336: 1152 to Susan Mayor “Enquiry shows poor care for patients with sickle cell disease” on National Confidential Enquiry into Patient Outcome and Death (NCEPOD) REPORT “SICKLE:  A Sickle Crisis? (2008) http://www.bmj.com/cgi/eletters/336/7654/1152a#196224 | http://www.info@ncepod.org

12 National Formulary. Pregabalin. BNF 70. September 2015 – March 2016: p 400.

13 Byrne Paul AC. Doctors are warned not to prescribe generic pregabalin for pain control www.bmj.com/content/350/bmj.h1734 March 30 2015 (BMJ April 7 2015)

14 Barbour James Re: Margaret McCartney – Second use of patents – why do we have to prescribe branded Lyrica for pain? (July 8 2015) “recent direction from a member of NHS health authorities that pregabalin prescriptions for chronic pain www.bmj.com/content/350/bmj,h1724/rapid-responses

15 McCartney Margaret. Second use of patents: Why do we have to prescribe branded Lyrica for pain? BMJ2015;350:h2734. July 8 2015.doi:10.1136/bmj.h2734 pmid:25995105

16 Leaver Laurence B. With friends like NHS England, GP’s do not need enemies “pregabalin to change some to Lyrica, so that Pfizer can maximise their profits at the expense of NHS” www.bmj.com/content/350/bmj.h1724 (02 May 2015)

17 Hopkins H. UK Government to reclassify pregabalin and gabapentin after rise in deaths. (03 October 2017) www.bmj.com/content/358/bmj.j4441 Rapid Response to Gareth Laccobucci. UK government to reclassify pregabalin and gabapentin after rise in deaths BMJ 2017; 358: 4441 https://doi.org/10.1136/bmj.j4441 (Published 25 September 2017) BMJ 2017;358:j4441

18 Rost Felicitas, Wessely Simon. Depression in adults: campaigners and doctors demand revision of NICE guidance. BMJ 2018;361:k2681 [BMJ 23 June 2018, p 426]  “The latest NICE draft guidelines on adult depression is misleading, invalid, not fit for purpose, and potentially harmful to patients”. BMJ 2018; 361: k2681.

19 Hurley Richard. Former MHRA chair takes job at cannabis investment company. Rapid Response Re: Cannabis, cannabis everywhere: UK to review medical cannabis policy as Canada plans imminent legislation for all uses. BMJ 20 June 2018 361:doi10.1136/bmj.k2695 “Sir Breckenridge will help Sativa Investments liaise with the Home Office and the Medicines and Healthcare products Regulatory Agency (“MHRA”), which he has chaired, for the legislation of medicinal cannabis in the UK”.

20 Konotey-Ahulu FID. Who should best pharmacovigilate in developing countries? https://www.bmj.com/rapid-response/2011/11/01/who-should-best-pharmacovigilate-developing-countries 14 September 2007 [ http://oW.ly/Dq8g30dSHe0 ]

21 Addae Stephen. Evolution Of Modern Medicine In A Developing Country: Ghana 1880 – 1960 Durham Academic Press, Ltd., 1 Hutton Close, Bishop Auckland, Durham 1996 [On Governor G Guggisberg and Le Fanu C V & Le Fanu G E H]

22 Goodall HB. Beloved Imperialist – Sir Gordon Guggisberg – Governor of The Gold Coast. The Penland Press Ltd., 1 Hutton Close, South Church, Bishop Auckland, Durham 1998.

23 Konotey-Ahulu FID. Some personal encounters with a remarkable physician (Tribute  to Dr Albert Joseph Hawe. OBE CBE MD FRCP DTMH). Ghana Med Journal 1979; 18: 88-90.

24 Le Fanu James. Too Many Pills – How too much medicine is endangering our health and what we can do about it. Little, Brown Book Group, London EC4Y 0DZ.

25 Daily Telegraph. Hospital drugs left 456 patients dead”. Thursday June 21 2018 Front Page. Editorial “Fatal doses of diamorphine and other inappropriate drugs”.

26 Le Fanu James. Mass medicalisation is an iatrogenic calamity. Profligate prescribing has brought a hidden a hidden epidemic of side effects and no benefit to most individuals. [PROVOCATIONS] BMJ 2018; 361: k2794. June 30, page 494.

27 [NOTE WELL]: Ballas S K. Sickle Cell Pain. IASP Press. Seattle, USA, page 168: “Diamorphine has no accepted medical use in the United States”

28 Konotey-Ahulu FID. Management of patients with sickle cell disease. African Journal of Health Sciences 1998; 5: 47[ Commenting on article of Sally Davies and Lola Oni (BMJ 315: 656 -60) “what I feel is more important in the day to day management of patients with a view to keeping them out of hospital, is clinical epidemiology which includes the circumstances of crises. … I fear Davies and Oni’s statement that ‘The Central Middlesex management protocol uses morphine infusions’ will make morphine the accepted drug for sickle crisis management. The consequences of such an approach are dire, especially when some UK hospitals are already making diamorphine their first choice”.]

29 Ringelhann B, Konotey-Ahulu FID. Hemoglobinopathies and thalassemias in Mediterranean areas and in West Africa: Historical and other perspectives 1910 to 1997 – A Century Review. Atti dell’Accademia dell Science di Ferrara (Milan) 1998;74: 267-307

30 Konotey-Ahulu FID. Opiates for pain in dying patients and in those with sickle cell disease. http://www.bmj.com/cgi/eetters/335/7622/685#177986 BMJ 11 Oct 2007

31 Konotey-Ahulu FID. Management of sickle cell disease versus management of the sickle cell disease patient. BMJ Rapid Response 17 September 2008

http://www.bmj.com/cgi/elettrs/337/sep08_1/a1397#202088

32 Konotey-Ahulu FID. Inquest into diamorphine deaths: Does NCEPOD sickle patients report warrant a similar inquest? BMJ Rapid Response March 7 2009

http://www.bmj.com/cgi/eletters/338/mar03_3/b903#210208

33 Konotey-Ahulu FID. Opiods for chronic non-cancer pain – Chemotherapy – Clinical Guidelines: Where does ultimate responsibility lie? www.bmj.com/content/ 346/bmj.f2937/rr/651421BMJ Rapid Response 25 June 2013

34 Konotey-Ahulu FID. Opiods in the UK: What’s the problem? Answer – Good Clinical Practice needs to cover all population groups including sickle cell disease patients. BMJ Rapid Response 18 August 2013 www.bmj.com/content/347/bmj.15108/rr/658208

35 Konotey-Ahulu FID. Management of sickle cell disease patient in the community BMJ Rapid Response 13 April 2014 [90 References] to Brousse V, Makali J, Rees DC: Management of sickle cell disease in the community. BMJ 2014; 348: g1765 doi:10.1136/bmj.g1765 http://www.bmj.com/content/348/bmj.g1765/rr/694233

36 Konotey-Ahulu FID. Management of an acute painful sickle cell episode in hospital: NICE guidance is frightening1 Sept 7 2012 [42 references]] www.bmj.com/content/344/bmj.e4063/rr/599158

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My PERSONAL VIEW on Research Integrity: When scientists confess to lying

My PERSONAL VIEW on Research Integrity: When scientists confess to lying
Dr Francis Crawley writes in the British Medical Journal 6 November, 2018: “The retraction of scientific articles based on fraudulent representations of science is damaging to science”. [1]. The terms “Research Integrity” and “Fraudulent Science” hide underneath a human umbrella of “Lying Scientists” or (using polished language) “Scientific Liars”.

EDITORIAL INTEGRITY OF BMJ & LANCET – PERSONAL EXPERIENCE

Great credit to these British Editors who pursued authors until they confessed uncomfortable truths leading to published articles retracted. I happened to be partly instrumental in unmasking in both these celebrated medical journals articles which (using Prime Minister Winston Churchill’s phrase) were full of “terminological in-exactitudes”, but which the Ghanaian in me would simply call “lies”.

In the BMJ example the then Editor rang me at Korle Bu Teaching Hospital to issue what amounted to an apology and to reassure me that the published fictitious Case Report would be withdrawn. This was done after the authors confessed to lying. What they said had happened in their Case Report had in fact not happened, because there was no Case(to)Report!

The second example of scientific erroneous data I was instrumental in unmasking was when the AIDS pandemic engulfed the world. The day my suspicions surfaced was when BBC WORLD SERVICE in its SCIENCE IN ACTION Programme May 3 1987 broadcast that the reason AIDS was rampant in Central Africa was that people there had inherited a new genetic factor that predisposed them and homosexuals to the virus. I had just finished touring the worst afflicted areas of my Continent at my own expense to study AIDS at the grassroots. I did the 16-countries’ trip expressly to study the epidemiology of the new disease at the village level. Both BMJ [2] and Lancet [3] published articles I submitted to them. No less than 4 other British International Journals including Journal of Royal Society of Medicine which even invited an Editorial [4], carried my novel epidemiological findings.

In my publications I told the world exactly why and how AIDS became rampant on my Enigmatic Continent, especially in my own Ghanaian Krobo tribe. Then, suddenly, there came a team of scientists from London University claiming that homosexuals and Central Africans shared a common gene that they blamed for the pandemic. I could not sit idly by when laboratory scientists could broadcast to the world what I considered to be false. The SCIENCE IN ACTION programme claimed The Lancet to be the source of its information. I read, and re-read the paper, and wrote to The Lancet whose august Editorial Team then comprised of Robin Fox, Imogen Evans, and David Sharpe. I called them “The Magnificent Trio” because I was invited to Lancet’s Offices 7 Adam Street, The Strand in London for interview to substantiate my African findings.

Mine was the very first correspondence in Lancet to criticize “the new research”. Stung by my statement that their research “leaves a lot to be desired” the authors wrote back to more or less rubbish what I said: “Konotey-Ahulu’s interpretation of our conclusions is at fault”. I kept quiet, and just let others continue with correspondence in Lancet. Some supported the homosexual/Central-African-gene “finding” while others including Dr S S Papiha from Newcastle University disagreed, supporting me. Professor A G Dalgleish from London University also commented. Meanwhile, the media had a field day. Science Editor of The Times (references available) went on, and on, about the genetics of why Africa was being decimated by AIDS.

Then, exactly 11 months and 3 weeks after the Lancet publication about which “The Magnificent Trio” allowed much correspondence doctors were amazed to read that because of “ERRONEAOUS DATA” (the authors’ own words) the article linking Central Africans and homosexuals was being retracted forthwith. Frankly, after decades writing in international journals, I have come to the conclusion that British Editors are head and shoulders above the Americans when it comes to retracting scientific misinformation. I once wrote to the USA correcting something about G6PD Deficiency occurring together with Sickle Cell Disease in the same patient, but it took more than 6 months for the New England Journal of Medicine to publish my concerns [5], by which time the original misinformation had taken root.

RETRACTION NOT MENTIONED IN WORLD PRESS

What was hugely worrying for us Africans was that although the scientists confessed to wrong doing in both the BMJ case and The Lancet, the media did not find it necessary to correct what had been said in SCIENCE IN ACTION or The Times. Indeed, it took Professor Hermann Lehmann FRS of Cambridge University writing to The Times (January 4 1972) to rebuke its Science Correspondent and ask why when misinformation had been confessed and withdrawn from the BMJ should articles continue to appear as if nothing had happened? The Times Correspondent (references available) continued also to publish the falsely claimed genetic proclivity of homosexuals and Central Africans to AIDS after the “Erroneous Data” confession.

It appears we Africans cannot win? Wrong! The number of cell phones pervading the Dark Continent is mind boggling! Refuse to correct Misinformation or Disinformation (defined as Deliberate Misinformation), and be sure to find it corrected on the Internet, and African drivers reading about it while filling their car tanks with petrol. The Media World has changed. Africans have handed in questions to be answered on Facebook “Meet the Professor talking about Sickle Cell Disease Patient Live” [6]. Those who miss the live programme can access the hour-long session later on YouTube. Let conventional media “forget” to correct confessed scientific in-exactitudes that had been retracted, and Twenty-First Century Social Media will NOT forget! Professor Lord Solly Zuckermann [7] and previous BMJ Editors Stephen Lock and Richard Smith [8 9] have written extensively about this very important matter.

[NOTE: References of names of authors who confessed to “erroneous data” after being challenged and have had articles withdrawn from BMJ and Lancet are withheld.]

Competing Interest: Having been Past Editor of Ghana Medical Journal for many years taught me to discern when authors’ research articles “left a lot to be desired”. [3]
felix@konotey-ahulu.com Twitter@profkonoteyahul
F I D Konotey-Ahulu MD(Lond) FRCP(Lond) DTMH(L’pool) Kwegyir Aggrey Distinguished Professor of Human Genetics, University of Cape Coast, Ghana and Former Consultant Physician Genetic Counsellor in Sickle Cell and Other Haemoglobinopathies, and Director Ghana Institute of Clinical GeneticsKorle Bu Teaching Hospital, Accra, Ghana and Phoenix Hospital Group, 9 Harley Street, London W1G 9AL [ www.sicklecell.md ]

References

1 Crawley Francis P. Research Integrity, Open Science, and Health Policy. BMJ Rapid Response 6 November 2018 https://www.bmj.com/content/363/bmj.k4309/rapid-responses

2 Konotey-Ahulu FID. Clinical epidemiology, not sero-epidemiology, is the answer to Africa’s AIDS problem BMJ (Clin Res Ed) 1987; 294(6587): 1593-1594 (June 20 1987)
http://www.bmj.com/cgi/reprint/294/6587/1593.pdf doi:10.1136/bmj.294.6587.1593

3 Konotey-Ahulu FID. AIDS in Africa: Misinformation and Disinformation. Lancet 1987; 2(8552): 206-208. July 25.

4 Konotey-Ahulu FID. An African on AIDS in Africa [Guest Editorial] The AIDS Letter – Royal Society of Medicine 1989 Feb/March, pp 1-3.http://www.konotey-ahulu.com/aidsinafrica/konoteyahulu/art1_cvref113.htm

5 Konotey-Ahulu FID. Glucose-6 phosphate dehydrogenase deficiency and sickle cell anaemia. New Eng J Med 1972; 287: 887-888. http://www.bmj.com/cgi/reprint/1/5793/177-a.pdf

6 Konotey-Ahulu FID. Meet the Professor talking about Sickle Cell disease patient live! Thursday 4th August 2016 7 pm On Line
https://www.facebook.com/events/1840398749523659/ | https://www.youtube.com/watch?v=TR-IENhqh5k

7 Zuckerman, Lord S. Pride and prejudice in Science. Aerospace Medicine 1974; 45: 638-647. [Describes a catalogue of frauds in Science over several decades]

8 Lock Stephen. Misconduct in medical research: Does it exist in Britain? BMJ December 10 1988, Volume 297, page 1531.

9 Smith Richard. Should research fraud be a criminal offence? The BMJ Opinion. December 9 2013 https://blogs.bmj.com [“A systematic review has shown that research misconduct is common, terrifyingly common. Anybody who is sceptical about research fraud should sign up to the brilliant Retraction Watch that will bring you several cases every week of scientific misconduct”]
9AL.