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User:Oceanflynn/sandbox/The Cholesterol Treatment Trialists’ (CTT) Collaboration

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Cholesterol Treatment Trialists’ Collaboration
Richard Doll Building
Established1994 (1994)
Location
Oxford University
,
UK
Websitewww.cttcollaboration.org

The Cholesterol Treatment Trialists’ Collaboration (CTT), which was co-founded in 1994 by researchers and co-directors Richard Doll and Rory Collins,[1] conducts meta-analysis of "large-scale (≥1000 participants), long-term (≥2 years scheduled treatment duration) randomized controlled trials of lipid intervention therapies." CTT is a joint collaboration by Clinical Trial Service Unit & Epidemiological Studies Unit at Oxford University in the United Kingdom and the National Health and Medical Research Council (NHMRC) Clinical Trials Centre (CTC) in Sydney, Australia. It is located in the Richard Doll Building (RDB) on the Old Road Campus, Oxford. "The CTT Collaboration is an international group which currently involves approximately 150 doctors, statisticians and research scientists, including experts in the field of cardiology, epidemiology, lipidology and clinical trials."[2]

The Clinical Trial Services Unit

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Main article: Clinical Trial Services Unit

The Clinical Trial Services Unit (CTSU), which was established by Richard Doll in 1975, is a medical research institute that conducts epidemiological studies and large-scale Phase III clinical trials on chronic diseases such as cancer and vascular conditions.[3] Major clinical trials run by the CTSU include Isis, the Heart Protection Study, Search and Sharp. The unit has also played key roles in the Kadoorie Study of Chronic Disease and the UK Biobank project.

History

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"Hence, in 1994, the decision was made to undertake periodic meta-analyses of individual participant data on mortality and morbidity from all relevant large-scale randomised trials of lipidmodifying treatments whose first results would be reported subsequently." The Lancet 2005

The CTT was established at the CTSU in 1994 and its initial protocol was published in 1995.[4]

Rory Collins "created and led large studies that transformed statins from esoteric drugs for familial hypercholesterolaemia into safe, widely-used generics that annually prevent millions of heart attacks and ischaemic strokes. His large placebo-controlled trials and worldwide Cholesterol Treatment Trialists’ meta-analyses confirmed heart attack reduction, discovered stroke reduction, and demonstrated safety and efficacy in many different types of patient."[5]Cite error: There are <ref> tags on this page without content in them (see the help page).[6][7][8]

Major projects

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By 2016 CTT had conducted meta-analysis of 23 large-scale, long-term randomized controlled trials of lipid intervention therapies. These studies collectively provided data from approximately 135,000 participants. The studies included Air Force/Texas Coronary Atherosclerosis Prevention (AFCAPS/TexCAPS 1998), Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN 2006) funded by Novartis and Pfizer[9], 4D 2005,[10] The Long-Term Interventionwith Pravastatin in Ischemic Disease (LIPID 1998-)[11], Scandinavian Simvastatin Survival Study (4S 1994),[12][13] ALERT 2003, AURORA funded by AstraZeneca, the manufacturer of Crestor rosuvastatin[14], Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico GISSI-HF (2008) funded by "Società Prodotti Antibiotici, Pfizer, Sigma Tau, and AstraZeneca."[15][16], LIPS 2002, SPARCL, The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT) 2002,[17] CARDS 2004, GISSI Prevention (GISSI-P 2000), MEGA, West of Scotland Coronary Prevention Study (WOSCOPS 1995)[18][19], ALLIANCE, CARE (1996), Heart Protection Study (HPS 2002),[20][21] POST-CABG (1997), Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-LLA) (2002) "Financial support mainly provided by Pfizer, manufacturer of Norvasc (amlodipine)."[22][23] Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA 2007) "Supported by AstraZeneca."[24][25] Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) 2008, sponsored by "AstraZeneca who collected the trial data and monitored study sites. Authors with multiple financial conflicts disclosed, including the primary author who owns the patent for the HS-CRP assay."[26][27] and PROSPER (2002)."[28] AHCAPS (1998), Individual trials of statin therapy that are part of CTT's meta-analyses may have been funded by the pharmaceutical industry. However, CTT is not funded by industry.[2]

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study was sponsored by the United States government through the National Heart, Lung, and Blood Institute (NHLBI), one of the Institutes at the federal National Institutes of Health. Abbott Laboratories, Amylin Pharmaceuticals, AstraZeneca Pharmaceuticals LP, Bayer HealthCare LLC, Closer Healthcare Inc., GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Inc., Merck & Company, Inc., Novartis Pharmaceuticals, Inc., Novo Nordisk Pharmaceuticals, Inc., Omron Healthcare, Inc., Sanofi-Aventis U.S., and Takeda Pharmaceuticals, Inc. donated study medications, equipment, or supplies for the ACCORD study.[29] The ACCORD trial found that "intensive compared with usual glycaemic management was associated with an increase in mortality [Gerstein et al. 2008], an observation that still remains largely unexplained [Boyko, 2010]."[30]

The Heart Protection Study was a large randomized controlled trial run by the Clinical Trial Service Unit, and funded by the Medical Research Council (MRC) and the British Heart Foundation (BHF) in the United Kingdom. It studied the use of statin (simvastatin 40 mg) medication and vitamin supplementation (vitamin E, vitamin C and beta carotene) in patients who are at risk of cardiovascular disease.[31][32][33][34][35]

..."heart attacks, strokes, revascularisation procedures, cause-specific mortality and cancers from about 30 such statin trials equating to approximately 175,000 individuals."[1]

Funding

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CTT is not funded by industry but individual trials of statin therapy may have been funded by the pharmaceutical industry.[2]

Publications

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  • 2012 May 17. Cholesterol Treatment Trialists' (CTT) Collaborators, Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, Collins R, Baigent C. "The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials." The Lancet. 2012 Aug; 380(9841):581-90. Epub 2012 May 17.
  • Lewington S; Whitlock G; Clarke R; Sherliker P; Emberson J; Halsey J; Qizilbash N; Peto R,; Collins R (December 2007). "Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths". The Lancet. 370 (9602): 1829–39. doi:10.1016/S0140-6736(07)61778-4. PMID 18061058. {{cite journal}}: Italic or bold markup not allowed in: |journal= (help)CS1 maint: extra punctuation (link) They inhibit the enzyme HMG-CoA reductase which plays a central role in the production of cholesterol. High cholesterol levels have been associated with cardiovascular disease (CVD).

Concerns

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"Collins and his team at Oxford University's clinical trials service unit are the only investigators who have seen the full patient-level data for some – but not all – of the statins trials. They formed the Cholesterol Treatment Trialists Collaboration to monitor and analyse statins data over the years. His critics point out that drug companies have helped fund his work."

In 2013 based on the work of CTT, the UK’s National Institute for Health and Clinical Excellence (Nice), advised doctors "to prescribe statins for patients with a low, 10% risk of heart disease in the next 10 years." This new recommendation doubled the number of people eligible for statins. Nice argued that if 4.5 million people who were basically healthy took statins, 28,000 heart attacks and 16,000 strokes would be prevented each year.[36]

In 2013, the British Medical Journal, which was "campaigning against the over-use of medicines and medical treatment",Cite error: The <ref> tag has too many names (see the help page). Draft guidance from the National Institute for Health and Care Excellence (Nice) "recommended that everybody with a risk as low as 10% over 10 years" should have access to statins.[37] In June 2014 nine doctors, including the president of the Royal College of Physicians, Sir Richard Thompson wrote to Nice questioning the "benefits and side-effects in low-risk people and claimed the true picture was distorted because drug companies had not put trial data into the public domain."[37][36] In May 2014 the two researchers whose articles were published in the BMJ 2013 "publicly retracted statements they made about the frequency of side effects experienced by people taking statins" following Collin's charge "that the information was wrong and could endanger lives."[37]

References

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  1. ^ a b "Research". Clinical Trial Services Unit. Clinical Trial Services Unit (CTSU). University of Oxford. nd. Retrieved December 5, 2016.
  2. ^ a b c "About", CTT Collaboration, retrieved December 5, 2016
  3. ^ "Welcome". Clinical Trial Services Unit]. University of Oxford. nd. Retrieved December 5, 2016.
  4. ^ "The Cholesterol Treatment Trialists' (CTT) Collaboration", CTT Collaboration, nd, retrieved December 5, 2016
  5. ^ "Sir Rory Collins FMedSci FRS". London: Royal Society. Archived from the original on 2015-11-17. One or more of the preceding sentences incorporates text from the royalsociety.org website where:

    “All text published under the heading 'Biography' on Fellow profile pages is available under Creative Commons Attribution 4.0 International License.” --Royal Society Terms, conditions and policies at the Wayback Machine (archived 25 September 2015)
  6. ^ Collaboration, A. T. (2002). "Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients". BMJ. 324 (7329): 71–86. doi:10.1136/bmj.324.7329.71. ISSN 0959-8138.
  7. ^ "MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial". The Lancet. 360 (9326): 7–22. 2002. doi:10.1016/S0140-6736(02)09327-3. ISSN 0140-6736.
  8. ^ Rory Collins' profile
  9. ^ The Lancet 2016
  10. ^ The Lancet 2005
  11. ^ [1]
  12. ^ 4S
  13. ^ Pedersen TR, et al. "Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)". The Lancet. 1994. 344(8934):1383-1389.
  14. ^ AURORA
  15. ^ GISSI-HF
  16. ^ Tavazzi L, et al. "Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure". The Lancet. 2008. 372(9645):1223-1230
  17. ^ JAMA. 2002 Dec 18;288(23):2998-3007. "Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)." ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.
  18. ^ Shepherd J; et al. (1995-11-16). "Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia". The New England Journal of Medicine. 333 (20): 1301–1308. PMID 7566020. {{cite journal}}: Explicit use of et al. in: |author= (help); Italic or bold markup not allowed in: |journal= (help)CS1 maint: date and year (link) Result: Pravastatin reduces MIs ]and CV mortality fulltexturl
  19. ^ WOSCOPS
  20. ^ Heart Protection Study
  21. ^ Heart Protection Study Collaborative Group Writers. "MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial". The Lancet. 2002. 360(9326):7-22.
  22. ^ ASCOT-BPLA
  23. ^ Dahlof et al. "Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm". The Lancet. 2005. 386:895-906.
  24. ^ CORONA
  25. ^ Kjekshus J, et al. "Rosuvastatin in Older Patients with Systolic Heart Failure". The New England Journal of Medicine. 2007. 357(22):2248-6
  26. ^ JUPITER
  27. ^ Ridker PM, et al. "Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein". The New England Journal of Medicine. 2008. 359(21):2195-2207.
  28. ^ "CTT Collaboration participating trials", CTT Collaboration, nd, retrieved December 5, 2016
  29. ^ ACCORD trial study funding
  30. ^ The case for more intensive use of statins 2012
  31. ^ "MRC/BHF Heart Protection Study of cholesterol-lowering therapy and of antioxidant vitamin supplementation in a wide range of patients at increased risk of coronary heart disease death: Early safety and efficacy experience". European Heart Journal. 20 (10): 725–41. 1999. doi:10.1053/euhj.1998.1350. PMID 10329064.
  32. ^ Heart Protection Study Collaborative Group (2002). "MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial". The Lancet. 360 (9326): 7–22. doi:10.1016/S0140-6736(02)09327-3. PMID 12114036.
  33. ^ Collins, R; Armitage, J; Parish, S; Sleigh, P; Peto, R; Heart Protection Study Collaborative Group (2003). "MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: A randomised placebo-controlled trial". Lancet (London, England). 361 (9374): 2005–16. doi:10.1016/s0140-6736(03)13636-7. PMID 12814710.
  34. ^ Collins, R; Armitage, J; Parish, S; Sleight, P; Peto, R; Heart Protection Study Collaborative Group (2004). "Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions". The Lancet. 363 (9411): 757–67. doi:10.1016/S0140-6736(04)15690-0. PMID 15016485.
  35. ^ Mihaylova, B; Briggs, A; Armitage, J; Parish, S; Gray, A; Collins, R; Heart Protection Study Collaborative Group (2005). "Cost-effectiveness of simvastatin in people at different levels of vascular disease risk: Economic analysis of a randomised trial in 20,536 individuals". The Lancet. 365 (9473): 1779–85. doi:10.1016/S0140-6736(05)63014-0. PMID 15910950.
  36. ^ a b Boseley, Sarah (September 2016). "Statins prevent 80,000 heart attacks and strokes a year in UK, study finds: Study in Lancet says risk of side-effects has been exaggerated and controversy will cause 2,000 extra heart attacks and strokes over next decade". The Guardian. Retrieved December 5, 2016. {{cite news}}: Italic or bold markup not allowed in: |publisher= (help)
  37. ^ a b c Boseley, Sarah (May 14, 2014). "BMJ rejects scare stories on statins following plea from Oxford professor: Collins says claims 18-20% of those on statins suffered side effects did 'disservice to British and international medicine'". The Guardian. Retrieved December 5, 2016. {{cite news}}: Italic or bold markup not allowed in: |publisher= (help)
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Category:Clinical trials related to cardiology Category:Cardiology Category:Epidemiological study projects Category:Research institutes established in 1994 Category:Clinical trial organizations Category:Departments of the University of Oxford

Major drug groups Statins Enzyme inhibition

Category:Medical research institutes in the United Kingdom

Category:Research institutes in the United Kingdom Category:Schools accredited by Category:1994 establishments in UK Category:Oxford University]] Category:La Jolla, San Diego]] Category:Non-profit organizations based in San Diego]]

Category:Statins

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