Ticagrelor: Considerable added benefit for specific patients
Since the start of 2011, the active ingredient ticagrelor can be prescribed in Germany in addition to acetylsalicylic acid (ASA) to avoid blood clots in patients with acute ischaemia of the cardiac muscle. The German Institute for Quality and Efficiency in Health Care (IQWiG) has now examined whether ticagrelor offers advantages to patients with acute coronary syndrome (ACS) in comparison with conventional drugs. This is the first co-called "early benefit assessment" that IQWiG has performed on the basis of a dossier provided by the manufacturer, in accordance with the new legal regulations.
The Institute has come to the conclusion that ticagrelor provides considerable added benefit to patients with "mild" myocardial infarction without the typical changes in the ECG (NSTEMI), as well as to patients with unstable angina pectoris, by reducing the risk of death and myocardial infarction. However, there is no corresponding proof for "severe" myocardial infarction (STEMI), in which there are usually characteristic changes in the ECG.
IQWiG assesses, G-BA decides
The company AstraZeneca developed the drug and introduced it to the German market at the start of 2011, under the trade name of Brillique®. On 1 January 2011, the German Act on the Reform of the Market for Medicinal Products (AMNOG) came into force, which lays down that new pharmaceuticals should regularly be subjected to a benefit assessment. For this purpose, the pharmaceutical company must submit a dossier containing proof of the added benefit, in comparison to the "appropriate comparator". The latter is specified by the Federal Joint Committee (G-BA).
The G-BA is responsible for the overall process, but can commission IQWiG to assess the manufacturer's dossier - as happened with ticagrelor. IQWiG then issues a recommendation as to how the added benefit is to be classified. After the commenting procedure, the G-BA reaches a formal decision on this added benefit. The assessment is only then complete.
Advantages in mortality and myocardial infarction
The G-BA specified clopidogrel as the appropriate comparator for the therapeutic indication of unstable angina pectoris or NSTEMI. On the basis of data from the PLATO study, the manufacturer could demonstrate that ticagrelor offers advantages to patients for this therapeutic indication. There were fewer deaths with ticagrelor than with clopidogrel. There were also fewer myocardial infarctions with ticagrelor, although it was not clear to what extent these were relevant to the analysis, i.e. were perceptible, myocardial infarctions.
No proof that severe bleeding events are more frequent
Drugs that inhibit parts of the blood clotting system generally also increase the risk of bleeding. However, severe bleeding events were no more frequent during treatment with ticagrelor than during treatment with clopidogrel. On the other hand, there was proof of more harm from ticagrelor with respect to study discontinuations due to adverse events and shortage of breath (dyspnoea).
Added benefit of intermediate category in patients with unstable angina pectoris and NSTEMI
After considering the individual results, IQWiG has classified the added benefit of ticagrelor in comparison with clopidogrel as being "considerable" in patients with unstable angina pectoris or NSTEMI. The legislator has classified three different degrees of added benefit - "minor", "considerable" and "major" in order to determine its extent. However, according to the legal requirements, the highest category should be reserved for drugs which give "persistent great improvement, which has not previously been seen". In other words, it must be regarded as a breakthrough in the treatment of the disease.
No proof of added benefit for patients with STEMI
The dossier failed to provide proof that ticagrelor is of added benefit for patients with STEMI. In patients whose coronary arteries had been expanded with a balloon catheter (PCI) after a STEMI, the comparison with prasugrel (another coagulation inhibitor) showed no advantages for ticagrelor. No informative data were provided by the manufacturer for patients who had only been given drug treatment after a STEMI or who had received a bypass operation. One reason for this was that AstraZeneca deviated from the appropriate comparator which the G-BA specified for the therapeutic indication "STEMI". In the opinion of IQWiG, AstraZeneca has not adequately justified this deviation, given that it was even partially inconsistent with the approval status of the coagulation inhibitors.
The law demands that benefits and harms should be balanced
According to the Institute's Director, Jürgen Windeler, "Myocardial infarctions and deaths are rarer with ticagrelor than with clopidogrel. However, there is also proof of more harm, such as increased dyspnoea. It is difficult to balance these advantages and disadvantages. Value judgements play a role here and to date there is no generally accepted scientific method for striking such a balance."
Nevertheless, IQWiG has to do this, as the legislator explicitly demands that a benefit assessment according to AMNOG should contain an overall conclusion, including a conclusion on the extent of the added benefit. According to Windeler, IQWiG has explained how they have arrived at the assessment of the different outcomes and how they have come to the overall conclusion. They explicitly wish this to be viewed as a suggestion. Not only the results, but also the methods could be discussed during the commenting procedure at the G-BA. They hope and wish that the procedure IQWiG has used in the case of ticagrelor will encourage scientific debate.
Patients and external experts involved
Both patients and external experts are regularly involved in the assessment of dossiers by IQWiG. Because of time limitations, this is mostly done by post. Medical advisors, generally specialists, and representatives of affected patients are sent questionnaires. This allows them to provide information about what they consider to be the important points for the treatment of the specific disease.
Practicable and transparent procedure
At the end of September 2011, IQWiG transmitted the dossier assessment to the G-BA, which then published it on 4 October 2011 - together with the manufacturer's dossier - and initiated the commenting procedure. It is planned that the G-BA will complete the assessment within three months of the publication. According to Thomas Kaiser, Head of the Department of Drug Assessment: "It is a real milestone, also internationally, that not only the IQWiG assessment is being published, but that the manufacturer has to disclose all relevant data. This is one reason why international experts are so interested in the early benefit assessment."
In IQWiG's opinion, the AMNOG procedure has passed its first practical test. Jürgen Windeler summarizes: "It is practicable and can be implemented in detail. The legal specifications have turned out to be appropriate. The first assessment certified that the drug shows added benefit and this demonstrates that the anxieties which have been expressed again and again by the pharmaceutical industry are unjustified. AMNOG does not present a threat to Germany as a site for industry."
Provided by Institute for Quality and Efficiency in Health Care
- Long struggle for appropriately processed manufacturer data leads to a new assessment of memantine Apr 27, 2011 | not rated yet | 0
- Breakthrough in drug trial offers hope for heart attack patients Sep 13, 2010 | not rated yet | 0
- One in five heart-attack deaths could be prevented with new drug Jun 13, 2011 | not rated yet | 0
- Benefit of blood glucose lowering to near-normal levels remains unclear Jul 14, 2011 | not rated yet | 0
- Elevated cholesterol levels: Benefit of ezetimibe is not proven Sep 14, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
Medical research 23 hours ago | not rated yet | 0 |
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
Medical research 23 hours ago | not rated yet | 0
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
Medical research May 23, 2013 | not rated yet | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
Medical research May 23, 2013 | 5 / 5 (3) | 0 |
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
Medical research May 23, 2013 | 5 / 5 (2) | 0
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
6 minutes ago | not rated yet | 0 |
Kate O'Reilly's spring allergy survival kit includes the usual stuff - nasal sprays, allergy pills and a box of tissues. This season, she's added a new weapon to her line of defense: an app on her smartphone.
47 minutes ago | not rated yet | 0
(AP)—Government health officials are investigating several health problems reported with potentially contaminated medications made by a Tennessee specialty pharmacy.
55 seconds ago | not rated yet | 0
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
5 hours ago | 5 / 5 (3) | 0 |
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
2 hours ago | not rated yet | 0 |
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
3 hours ago | 5 / 5 (2) | 0 |