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

The Cholesterol Treatment Trialists’ Collaboration (CTT), which was co-founded in 1994 by researchers and co-directors Richard Doll and Rory Collins, 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."

The 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. 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
""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.

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."

Major projects
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, 4D 2005, The Long-Term Interventionwith Pravastatin in Ischemic Disease (LIPID 1998-) , Scandinavian Simvastatin Survival Study (4S 1994), ALERT 2003, AURORA funded by AstraZeneca, the manufacturer of Crestor rosuvastatin , Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico GISSI-HF (2008) funded by "Società Prodotti Antibiotici, Pfizer, Sigma Tau, and AstraZeneca." , LIPS 2002, SPARCL, The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT) 2002, CARDS 2004, GISSI Prevention (GISSI-P 2000), MEGA, West of Scotland Coronary Prevention Study (WOSCOPS 1995), ALLIANCE, CARE (1996), Heart Protection Study (HPS 2002),  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)." Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA 2007) "Supported by AstraZeneca." 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." and PROSPER (2002)." 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.

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. 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]."

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.

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

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

Publications

 * 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.


 * 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
""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.

In 2013, the British Medical Journal, which was "campaigning against the over-use of medicines and medical treatment",<ref name="theguardian_2016" published two articles in which researchers claimed that "statins in low-risk patients did not reduce mortality" and that in that group, "the side-effects meant they sometimes did more harm than good." 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. 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." 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."