Clinical research is a branch of medical research that involves people and aims to determine the effectiveness ( efficacy ) and safety of medications , devices , diagnostic products , and treatment regimens intended for improving human health. These research procedures are designed for the prevention, treatment, diagnosis or understanding of disease symptoms.
136-399: Clinical research is different from clinical practice: in clinical practice, established treatments are used to improve the condition of a person, while in clinical research, evidence is collected under rigorous study conditions on groups of people to determine the efficacy and safety of a treatment. The term "clinical research" refers to the entire process of studying and writing about a drug,
272-442: A sui generis political entity combining the characteristics of both a federation and a confederation . Containing 5.8% of the world population in 2020, EU member states generated a nominal gross domestic product (GDP) of around US$ 16.6 trillion in 2022, constituting approximately one sixth of global nominal GDP . Additionally, all EU states except Bulgaria have a very high Human Development Index according to
408-688: A European customs union for the struggling post-war European economies, and in 1923 the oldest organisation for European integration, the Paneuropean Union was founded, led by Richard von Coudenhove-Kalergi , who later would found in June 1947 the European Parliamentary Union (EPU). Aristide Briand —who was Prime Minister of France , a follower of the Paneuropean Union, and Nobel Peace Prize laureate for
544-669: A proposal that linked funding with adherence to the rule of law . The budget included a COVID-19 recovery fund of €750 billion. The budget may still be approved if Hungary and Poland withdraw their vetoes after further negotiations in the council and the European Council . Bodies combatting fraud have also been established, including the European Anti-fraud Office and the European Public Prosecutor's Office . The latter
680-529: A " collective head of state " and ratifies important documents (for example, international agreements and treaties). Tasks for the president of the European Council are ensuring the external representation of the EU, driving consensus and resolving divergences among member states, both during meetings of the European Council and over the periods between them. The European Council should not be mistaken for
816-611: A broad forum to further cooperation and shared issues, achieving for example the European Convention on Human Rights in 1950. Essential for the actual birth of the institutions of the EU was the Schuman Declaration on 9 May 1950 (the day after the fifth Victory in Europe Day ) and the decision by six nations (France, Belgium, Netherlands, Luxembourg, West Germany and Italy) to follow Schuman and draft
952-415: A dietary supplement of an acidic quality in the experiment after two months at sea, when the ship was already afflicted with scurvy. He divided twelve scorbutic sailors into six groups of two. They all received the same diet but, in addition, group one was given a quart of cider daily, group two twenty-five drops of elixir of vitriol ( sulfuric acid ), group three six spoonfuls of vinegar , group four half
1088-461: A different purpose to construct focus on identifying a specific effect. Clinical trials involving new drugs are commonly classified into five phases. Each phase of the drug approval process is treated as a separate clinical trial. The drug development process will normally proceed through phases I–IV over many years, frequently involving a decade or longer. If the drug successfully passes through phases I, II, and III, it will usually be approved by
1224-419: A landmark study carried out in collaboration with Richard Doll on the correlation between smoking and lung cancer . They carried out a case-control study in 1950, which compared lung cancer patients with matched control and also began a sustained long-term prospective study into the broader issue of smoking and health, which involved studying the smoking habits and health of more than 30,000 doctors over
1360-458: A medical device or a form of treatment, which includes conducting interventional studies ( clinical trials ) or observational studies on human participants. Clinical research can cover any medical method or product from its inception in the lab to its introduction to the consumer market and beyond. Once the promising candidate or the molecule is identified in the lab, it is subjected to pre-clinical studies or animal studies where different aspects of
1496-557: A national regulatory authority approves marketing of the innovation. Similarly to drugs, manufacturers of medical devices in the United States are required to conduct clinical trials for premarket approval . Device trials may compare a new device to an established therapy, or may compare similar devices to each other. An example of the former in the field of vascular surgery is the Open versus Endovascular Repair (OVER trial) for
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#17327828909401632-434: A panel of expert clinical investigators, including what alternative or existing treatments to compare to the new drug and what type(s) of patients might benefit. If the sponsor cannot obtain enough test subjects at one location investigators at other locations are recruited to join the study. During the trial, investigators recruit subjects with the predetermined characteristics, administer the treatment(s) and collect data on
1768-499: A period of several years. His certificate for election to the Royal Society called him "... the leader in the development in medicine of the precise experimental methods now used nationally and internationally in the evaluation of new therapeutic and prophylactic agents ." International clinical trials day is celebrated on 20 May. The acronyms used in the titling of clinical trials are often contrived, and have been
1904-546: A permanent president of the European Council , the first of which was Herman Van Rompuy , and strengthened the position of the high representative of the union for foreign affairs and security policy . In 2012, the EU received the Nobel Peace Prize for having "contributed to the advancement of peace and reconciliation, democracy, and human rights in Europe". In 2013, Croatia became the 28th EU member. From
2040-465: A pint of seawater, group five received two oranges and one lemon , and the last group a spicy paste plus a drink of barley water . The treatment of group five stopped after six days when they ran out of fruit, but by then one sailor was fit for duty while the other had almost recovered. Apart from that, only group one also showed some effect of its treatment. Each year, May 20 is celebrated as Clinical Trials Day in honor of Lind's research. After 1750
2176-412: A placebo to a person suffering from a disease may be unethical, "active comparator" (also known as "active control") trials may be conducted instead. In trials with an active control group, subjects are given either the experimental treatment or a previously approved treatment with known effectiveness. In other cases, sponsors may conduct an active comparator trial to establish an efficacy claim relative to
2312-549: A pooled military aid package to Ukraine for lethal weapons funded via the European Peace Facility off-budget instrument. Next Generation EU ( NGEU ) is a European Commission economic recovery package to support the EU member states to recover from the COVID-19 pandemic , in particular those that have been particularly hard hit. It is sometimes styled NextGenerationEU and Next Gen EU , and also called
2448-460: A possibility of strong changes in the 2024 elections. Since the end of World War II , sovereign European countries have entered into treaties and thereby co-operated and harmonised policies (or pooled sovereignty ) in an increasing number of areas, in the European integration project or the construction of Europe ( French : la construction européenne ). The following timeline outlines
2584-713: A post-war world and Europe increasingly became a part of the agenda. This led to a decision at the Yalta Conference in 1944 to form a European Advisory Commission , later replaced by the Council of Foreign Ministers and the Allied Control Council , following the German surrender and the Potsdam Agreement in 1945. By the end of the war, European integration became seen as an antidote to
2720-598: A right of unilateral withdrawal under Article 50 of the Treaty on European Union. In addition, the principle of subsidiarity requires that only those matters that need to be determined collectively are so determined. Under the principle of supremacy , national courts are required to enforce the treaties that their member states have ratified, even if doing so requires them to ignore conflicting national law, and (within limits) even constitutional provisions. The direct effect and supremacy doctrines were not explicitly set out in
2856-779: A role in clinical trials. While working for the Rothamsted experimental station in the field of agriculture, Fisher developed his Principles of experimental design in the 1920s as an accurate methodology for the proper design of experiments. Among his major ideas include the importance of randomization —the random assignment of individuals to different groups for the experiment; replication —to reduce uncertainty , measurements should be repeated and experiments replicated to identify sources of variation; blocking —to arrange experimental units into groups of units that are similar to each other, and thus reducing irrelevant sources of variation; use of factorial experiments —efficient at evaluating
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#17327828909402992-422: A service. They can also help to make the research more grounded in the needs of the specific communities they are part of. Public contributors can also ensure that the research is presented in plain language that is clear to the wider society and the specific groups it is most relevant for. Following preclinical research , clinical trials involving new drugs are commonly classified into four phases. Each phase of
3128-732: A set number of seats and is divided into sub-national constituencies where this does not affect the proportional nature of the voting system. In the ordinary legislative procedure , the European Commission proposes legislation, which requires the joint approval of the European Parliament and the Council of the European Union to pass. This process applies to nearly all areas, including the EU budget . The parliament
3264-420: A similar cutoff age) are often excluded from trials because their greater health issues and drug use complicate data interpretation, and because they have different physiological capacity than younger people. Children and people with unrelated medical conditions are also frequently excluded. Pregnant women are often excluded due to potential risks to the fetus . The sponsor designs the trial in coordination with
3400-751: A similar fashion for studies conducted in their region. These human studies are conducted in four phases in research subjects that give consent to participate in the clinical trials. Clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines , drugs , dietary choices , dietary supplements , and medical devices ) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in
3536-540: A single disease entering and leaving the platform), and basket trial (one medical product for multiple diseases or disease subtypes). Genetic testing enables researchers to group patients according to their genetic profile, deliver drugs based on that profile to that group and compare the results. Multiple companies can participate, each bringing a different drug. The first such approach targets squamous cell cancer , which includes varying genetic disruptions from patient to patient. Amgen, AstraZeneca and Pfizer are involved,
3672-491: A single research center or multiple centers , in one country or in multiple countries. Clinical study design aims to ensure the scientific validity and reproducibility of the results. Costs for clinical trials can range into the billions of dollars per approved drug, and the complete trial process to approval may require 7–15 years. The sponsor may be a governmental organization or a pharmaceutical , biotechnology or medical-device company. Certain functions necessary to
3808-423: A treatment can have nonspecific effects. These are controlled for by the inclusion of patients who receive only a placebo. Subjects are assigned randomly without informing them to which group they belonged. Many trials are doubled-blinded so that researchers do not know to which group a subject is assigned. Assigning a subject to a placebo group can pose an ethical problem if it violates his or her right to receive
3944-646: Is a decentralized independent body of the European Union (EU), established under the Treaty of Lisbon between 22 of the 27 states of the EU following the method of enhanced cooperation . The European Public Prosecutor's Office investigate and prosecute fraud against the budget of the European Union and other crimes against the EU's financial interests including fraud concerning EU funds of over €10,000 and cross-border VAT fraud cases involving damages above €10 million. Member states retain in principle all powers except those that they have agreed collectively to delegate to
4080-640: Is based in Kirchberg, Luxembourg City alongside the Court of Justice of the European Union and the European Court of Auditors. Constitutionally, the EU bears some resemblance to both a confederation and a federation , but has not formally defined itself as either. (It does not have a formal constitution: its status is defined by the Treaty of European Union and the Treaty on the Functioning of
4216-467: Is inconsistent with EU law. It is not possible to appeal against the decisions of national courts in the CJEU, but rather national courts refer questions of EU law to the CJEU. However, it is ultimately for the national court to apply the resulting interpretation to the facts of any given case. Although, only courts of final appeal are bound to refer a question of EU law when one is addressed. The treaties give
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4352-587: Is known as patient and public involvement (PPI). Public involvement involves a working partnership between patients, caregivers, people with lived experience, and researchers to shape and influence what is researched and how. PPI can improve the quality of research and make it more relevant and accessible. People with current or past experience of illness can provide a different perspective than professionals and compliment their knowledge. Through their personal knowledge they can identify research topics that are relevant and important to those living with an illness or using
4488-598: Is organised as a directorial system , where the executive power is jointly exercised by several people. The executive branch consists of the European Council and European Commission. The European Council sets the broad political direction of the Union. It convenes at least four times a year and comprises the president of the European Council (presently Charles Michel ), the president of the European Commission and one representative per member state (either its head of state or head of government ). The high representative of
4624-562: Is regulated to try to balance the aspirations of private initiatives with public interest decision-making process. The European Union had an agreed budget of €170.6 billion in 2022. The EU had a long-term budget of €1,082.5 billion for the period 2014–2020, representing 1.02% of the EU-28's GNI. In 1960, the budget of the European Community was 0.03 per cent of GDP. Of this, €54bn subsidised agriculture enterprise , €42bn
4760-420: Is researcher and how. PPI can improve the quality of research and make it more relevant and accessible. People with current or past experience of illness can provide a different perspective than professionals and compliment their knowledge. Through their personal knowledge they can identify research topics that are relevant and important to those living with an illness or using a service. They can also help to make
4896-512: Is the final body to approve or reject the proposed membership of the commission, and can attempt motions of censure on the commission by appeal to the Court of Justice . The president of the European Parliament carries out the role of speaker in Parliament and represents it externally. The president and vice-presidents are elected by MEPs every two and a half years. The judicial branch of
5032-485: Is then able to recruit staff from among the pool of candidates selected by EPSO. On average, EPSO receives around 60,000–70,000 applications a year with around 1,500–2,000 candidates recruited by the European Union institutions. The European Ombudsman is the ombudsman branch of the European Union that holds the institutions, bodies and agencies of the EU to account, and promotes good administration. The Ombudsman helps people, businesses and organisations facing problems with
5168-578: Is to prove safety and an effective dosage. Phase II includes a larger number of individual participants in the range of 100–300, and Phase III includes some 1000-3000 participants to assess efficacy and safety of the drug at different doses. Only 25-30% of drugs advance to the end of Phase III. In the United States , when a test article is unapproved or not yet cleared by the Food and Drug Administration ( FDA ), or when an approved or cleared test article
5304-469: Is used in a way that may significantly increase the risks (or decreases the acceptability of the risks), the data obtained from the preclinical studies or other supporting evidence, or case studies of off label use are submitted to the FDA in support of an Investigational New Drug application. Where devices are concerned the submission to the FDA would be for an Investigational Device Exemption application if
5440-704: The Common Foreign and Security Policy , the union has developed a role in external relations and defence . It maintains permanent diplomatic missions throughout the world and represents itself at the United Nations , the World Trade Organization , the G7 and the G20 . Due to its global influence, the European Union has been described by some scholars as an emerging superpower . The EU
5576-669: The Council of Europe , an international organisation independent of the EU and based in Strasbourg. The European Commission acts both as the EU's executive arm , responsible for the day-to-day running of the EU, and also the legislative initiator , with the sole power to propose laws for debate. The commission is 'guardian of the Treaties' and is responsible for their efficient operation and policing. It has 27 European commissioners for different areas of policy, one from each member state, though commissioners are bound to represent
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5712-547: The Court of Justice of the European Union , the European Central Bank and the European Court of Auditors . Competence in scrutinising and amending legislation is shared between the Council of the European Union and the European Parliament, while executive tasks are performed by the European Commission and in a limited capacity by the European Council (not to be confused with the aforementioned Council of
5848-742: The Declaration of St James's Palace of 1941, when Europe's resistance gathered in London. This was expanded on by the 1941 Atlantic Charter , establishing the Allies and their common goals, inciting a new wave of global international institutions like the United Nations ( founded 1945 ) or the Bretton Woods System (1944). In 1943 at the Moscow Conference and Tehran Conference , plans to establish joint institutions for
5984-512: The European Union Recovery Instrument . Agreed in principle by the European Council on 21 July 2020 and adopted on 14 December 2020, the instrument is worth € 750 billion . NGEU will operate from 2021 to 2026, and will be tied to the regular 2021–2027 budget of the EU's Multiannual Financial Framework (MFF). The comprehensive NGEU and MFF packages are projected to reach €1824.3 billion. Preparing
6120-634: The French Union was installed by the new Fourth French Republic to direct the decolonization of its colonies so that they would become parts of a European community. By 1947 a growing rift between the western Allied Powers and the Soviet Union became evident as a result of the rigged 1947 Polish legislative election , which constituted an open breach of the Yalta Agreement . March of that year saw two important developments. First
6256-571: The Locarno Treaties —delivered a widely recognized speech at the League of Nations in Geneva on 5 September 1929 for a federal Europe to secure Europe and settle the historic Franco-German enmity . With large-scale war being waged in Europe once again in the 1930s and becoming World War II , the question of what to fight against and what for, had to be agreed on. A first agreement was
6392-571: The Therapeutic Trials Committee to advise and assist in the arrangement of properly controlled clinical trials on new products that seem likely on experimental grounds to have value in the treatment of disease. The first randomised curative trial was carried out at the MRC Tuberculosis Research Unit by Sir Geoffrey Marshall (1887–1982). The trial, carried out between 1946 and 1947, aimed to test
6528-920: The Treaty of Brussels was signed, establishing the Western Union (WU), followed by the International Authority for the Ruhr . Furthermore, the Organisation for European Economic Co-operation (OEEC), the predecessor of the OECD, was also founded in 1948 to manage the Marshall Plan , which led to the Soviets creating Comecon in response. The ensuing Hague Congress of May 1948 was a pivotal moment in European integration, as it led to
6664-716: The Treaty of Paris . This treaty was created in 1952 the European Coal and Steel Community (ECSC), which was built on the International Authority for the Ruhr , installed by the Western Allies in 1949 to regulate the coal and steel industries of the Ruhr area in West Germany. Backed by the Marshall Plan with large funds coming from the United States since 1948, the ECSC became a milestone organisation, enabling European economic development and integration and being
6800-547: The United Kingdom . Norway had negotiated to join at the same time, but Norwegian voters rejected membership in a referendum . The Ostpolitik and the ensuing détente led to establishment of a first truly pan-European body, the Conference on Security and Co-operation in Europe (CSCE), predecessor of the modern Organization for Security and Co-operation in Europe (OSCE). In 1979, the first direct elections to
6936-559: The United Nations Development Programme . Its cornerstone, the Customs Union , paved the way to establishing an internal single market based on standardised legal framework and legislation that applies in all member states in those matters, and only those matters, where the states have agreed to act as one. EU policies aim to ensure the free movement of people, goods, services and capital within
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#17327828909407072-607: The Western Union , the International Authority for the Ruhr , the European Coal and Steel Community , the European Economic Community and the European Atomic Energy Community , which were established by treaties. These increasingly amalgamated bodies grew, with their legal successor the EU, both in size through the accessions of a further 22 states from 1973 to 2013, and in power through acquisitions of policy areas. In 2012,
7208-409: The cohort study and the case-control study , provide less compelling evidence than the randomized controlled trial. In observational studies, the investigators retrospectively assess associations between the treatments given to participants and their health status, with potential for considerable errors in design and interpretation. A randomized controlled trial can provide compelling evidence that
7344-687: The extreme nationalism that had caused the war. On 19 September 1946, in a much recognized speech, Winston Churchill , speaking at the University of Zürich , reiterated his calls since 1930 for a "European Union" and "Council of Europe", coincidentally parallel to the Hertenstein Congress of the Union of European Federalists , one of the then founded and later constituting members of the European Movement . One month later,
7480-635: The monetary branch of the European Union, the prime component of the Eurosystem and the European System of Central Banks. It is one of the world's most important central banks . The ECB Governing Council makes monetary policy for the Eurozone and the European Union, administers the foreign exchange reserves of EU member states, engages in foreign exchange operations, and defines the intermediate monetary objectives and key interest rate of
7616-447: The principle of conferral (which says that it should act only within the limits of the competences conferred on it by the treaties ) and of subsidiarity (which says that it should act only where an objective cannot be sufficiently achieved by the member states acting alone). Laws made by the EU institutions are passed in a variety of forms. Generally speaking, they can be classified into two groups: those which come into force without
7752-612: The 1960s, tensions began to show, with France seeking to limit supranational power. Nevertheless, in 1965 an agreement was reached, and on 1 July 1967 the Merger Treaty created a single set of institutions for the three communities, which were collectively referred to as the European Communities . Jean Rey presided over the first merged commission ( Rey Commission ). In 1973, the communities were enlarged to include Denmark (including Greenland), Ireland, and
7888-478: The CJEU the power for consistent application of EU law across the EU as a whole. The court also acts as an administrative and constitutional court between the other EU institutions and the Member States and can annul or invalidate unlawful acts of EU institutions, bodies, offices and agencies. The General Court is a constituent court of the European Union. It hears actions taken against the institutions of
8024-417: The Council of the European Union and the "Council of Ministers", its former title), forms one half of the EU's legislature. It consists of a representative from each member state's government and meets in different compositions depending on the policy area being addressed . Notwithstanding its different configurations, it is considered to be one single body. In addition to the legislative functions, members of
8160-560: The ECB and the national central banks (NCBs) of all 27 member states of the European Union. The ESCB is not the monetary authority of the eurozone, because not all EU member states have joined the euro. The ESCB's objective is price stability throughout the European Union. Secondarily, the ESCB's goal is to improve monetary and financial cooperation between the Eurosystem and member states outside
8296-401: The EU administration by investigating complaints, as well as by proactively looking into broader systemic issues. The current Ombudsman is Emily O'Reilly . The European Public Prosecutor's Office (EPPO) is the prosecutory branch of the union with juridical personality, established under the Treaty of Lisbon between 23 of the 27 states of the EU following the method of enhanced cooperation. It
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#17327828909408432-474: The EU was awarded the Nobel Peace Prize . The United Kingdom became the only member state to leave the EU , in 2020; ten countries are aspiring or negotiating to join it . Internationalism and visions of European unity had existed since well before the 19th century, but gained particularly as a reaction to World War I and its aftermath. In this light the first advances for the idea of European integration were made. In 1920 John Maynard Keynes proposed
8568-420: The EU, which together with the Council of the European Union is tasked with amending and approving the European Commission's proposals. 705 members of the European Parliament (MEPs) are directly elected by EU citizens every five years on the basis of proportional representation . MEPs are elected on a national basis and they sit according to political groups rather than their nationality. Each country has
8704-436: The EU. The ECB Executive Board enforces the policies and decisions of the Governing Council, and may direct the national central banks when doing so. The ECB has the exclusive right to authorise the issuance of euro banknotes . Member states can issue euro coins , but the volume must be approved by the ECB beforehand. The bank also operates the TARGET2 payments system. The European System of Central Banks (ESCB) consists of
8840-437: The Euro . After the economic crisis caused by the COVID-19 pandemic , the EU leaders agreed for the first time to create common debt to finance the European Recovery Program called Next Generation EU (NGEU). On 24 February 2022, after massing on the borders of Ukraine, the Russian Armed Forces undertook an attempt for a full-scale invasion of Ukraine. The European Union imposed heavy sanctions on Russia and agreed on
8976-400: The European Community and the EU, and then made amendments to those founding treaties. These are power-giving treaties which set broad policy goals and establish institutions with the necessary legal powers to implement those goals. These legal powers include the ability to enact legislation which can directly affect all member states and their inhabitants. The EU has legal personality , with
9112-428: The European Council of its decision to leave on 29 March 2017, initiating the formal withdrawal procedure for leaving the EU ; following extensions to the process, the UK left the European Union on 31 January 2020, though most areas of EU law continued to apply to the UK for a transition period which lasted until 31 December 2020. The early 2020s saw Denmark abolishing one of its three opt-outs and Croatia adopting
9248-420: The European Council. The other 25 commissioners are subsequently appointed by the Council of the European Union in agreement with the nominated president. The 27 commissioners as a single body are subject to approval (or otherwise) by a vote of the European Parliament . All commissioners are first nominated by the government of the respective member state. The council, as it is now simply called (also called
9384-420: The European Parliament were held. Greece joined in 1981. In 1985, Greenland left the Communities , following a dispute over fishing rights. During the same year, the Schengen Agreement paved the way for the creation of open borders without passport controls between most member states and some non-member states. In 1986, the Single European Act was signed. Portugal and Spain joined in 1986. In 1990, after
9520-432: The European Treaties but were developed by the Court of Justice itself over the 1960s, apparently under the influence of its then most influential judge, Frenchman Robert Lecourt . The question whether the secondary law enacted by the EU has a comparable status in relation to national legislation, has been a matter of debate among legal scholars. The European Union is based on a series of treaties . These first established
9656-402: The European Union by individuals and member states, although certain matters are reserved for the Court of Justice. Decisions of the General Court can be appealed to the Court of Justice, but only on a point of law. Prior to the coming into force of the Lisbon Treaty on 1 December 2009, it was known as the Court of First Instance. The European Central Bank (ECB) is one of the institutions of
9792-410: The European Union ). It is more integrated than a traditional confederation of states because the general level of government widely employs qualified majority voting in some decision-making among the member states, rather than relying exclusively on unanimity. It is less integrated than a federal state because it is not a state in its own right: sovereignty continues to flow 'from the bottom up', from
9928-481: The European Union is formally called the Court of Justice of the European Union (CJEU) and consists of two courts: the Court of Justice and the General Court . The Court of Justice is the supreme court of the European Union in matters of European Union law . As a part of the CJEU, it is tasked with interpreting EU law and ensuring its uniform application across all EU member states under Article 263 of
10064-554: The European Union). The monetary policy of the eurozone is determined by the European Central Bank. The interpretation and the application of EU law and the treaties are ensured by the Court of Justice of the European Union. The EU budget is scrutinised by the European Court of Auditors. There are also a number of ancillary bodies which advise the EU or operate in a specific area. The Union's executive branch
10200-516: The Netherlands , and West Germany signed the Treaty of Rome , which created the European Economic Community (EEC) and established a customs union . They also signed another pact creating the European Atomic Energy Community (Euratom) for cooperation in developing nuclear power. Both treaties came into force in 1958. Although the EEC and Euratom were created separately from the ECSC, they shared
10336-782: The Soviets. Immediately following the February 1948 coup d'état by the Communist Party of Czechoslovakia , the London Six-Power Conference was held, resulting in the Soviet boycott of the Allied Control Council and its incapacitation, an event marking the beginning of the Cold War . The year 1948 marked the beginning of the institutionalised modern European integration . In March 1948
10472-541: The Treaty of the Functioning of the European Union (TFEU). The Court was established in 1952, and is based in Luxembourg . It is composed of one judge per member state – currently 27 – although it normally hears cases in panels of three, five or fifteen judges. The Court has been led by president Koen Lenaerts since 2015. The CJEU is the highest court of the European Union in matters of Union law . Its case-law provides that EU law has supremacy over any national law that
10608-466: The UK also follow ICH guidelines. Journals such as Trials , encourage investigators to publish their protocols. Clinical trials recruit study subjects to sign a document representing their " informed consent ". The document includes details such as its purpose, duration, required procedures, risks, potential benefits, key contacts and institutional requirements. The participant then decides whether to sign
10744-430: The Union as a whole, though the exact delimitation has on occasions become a subject of scholarly or legal disputes. In certain fields, members have awarded exclusive competence and exclusive mandate to the Union. These are areas in which member states have entirely renounced their own capacity to enact legislation. In other areas, the EU and its member states share the competence to legislate. While both can legislate,
10880-554: The Union for a new great enlargement is a political priority for the Union, with the goal of achieving over 35 member states by 2030. Institutional and budgetary reforms are being discussed in order to the Union to be ready for the new members. In May 2024, concerns rise, that the outcome of the elections in June, can undermine some of the crucial policies of the EU in the domain of environment, diplomacy, economy . The war in Ukraine by creating inflation, lowering life level created
11016-675: The WEU and NATO in 1955, prompting the Soviet Union to form the Warsaw Pact in 1955 as an institutional framework for its military domination in the countries of Central and Eastern Europe . Assessing the progress of European integration the Messina Conference was held in 1955, ordering the Spaak report , which in 1956 recommended the next significant steps of European integration. In 1957, Belgium , France , Italy , Luxembourg ,
11152-412: The ability of a trial to detect a difference of a particular size (or larger) between the treatment and control groups. For example, a trial of a lipid -lowering drug versus placebo with 100 patients in each group might have a power of 0.90 to detect a difference between placebo and trial groups receiving dosage of 10 mg/dL or more, but only 0.70 to detect a difference of 6 mg/dL. Merely giving
11288-428: The academic institution as well as access to larger metropolitan areas, providing a larger pool of medical participants. These academic medical centers often have their internal Institutional Review Boards that oversee the ethical conduct of medical research. Besides being participants in a clinical trial, members of the public can actively collaborate with researchers in designing and conducting clinical research. This
11424-454: The active comparator instead of the placebo in labeling . A master protocol includes multiple substudies, which may have different objectives and involve coordinated efforts to evaluate one or more medical products in one or more diseases or conditions within the overall study structure. Trials that could develop a master protocol include the umbrella trial (multiple medical products for a single disease), platform trial (multiple products for
11560-464: The beginning of the 2010s, the cohesion of the European Union has been tested by several issues, including a debt crisis in some of the Eurozone countries , a surge in asylum seekers in 2015 , and the United Kingdom's withdrawal from the EU . A referendum in the UK on its membership of the European Union was held in 2016, with 51.9 per cent of participants voting to leave. The UK formally notified
11696-527: The best available treatment. The Declaration of Helsinki provides guidelines on this issue. European Union in Europe (dark grey) The European Union ( EU ) is a supranational political and economic union of 27 member states that are located primarily in Europe. The Union has a total area of 4,233,255 km (1,634,469 sq mi) and an estimated total population of over 449 million. The EU has often been described as
11832-530: The catastrophic result of Anson 's circumnavigation attracted much attention in Europe; out of 1900 men, 1400 had died, most of them allegedly from having contracted scurvy. John Woodall , an English military surgeon of the British East India Company , had recommended the consumption of citrus fruit from the 17th century, but their use did not become widespread. Lind conducted the first systematic clinical trial in 1747. He included
11968-407: The clinical trial to follow. There are two goals to testing medical treatments: to learn whether they work well enough, called "efficacy", or "effectiveness"; and to learn whether they are safe enough, called "safety". Neither is an absolute criterion; both safety and efficacy are evaluated relative to how the treatment is intended to be used, what other treatments are available, and the severity of
12104-416: The council also have executive responsibilities, such as the development of a Common Foreign and Security Policy and the coordination of broad economic policies within the Union. The Presidency of the council rotates between member states, with each holding it for six months. Beginning on 1 July 2024, the position is held by Hungary. The European Parliament is one of three legislative institutions of
12240-509: The country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small pilot studies , and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary in size and cost, and they can involve
12376-574: The creation of the European Movement International , the College of Europe and most importantly to the foundation of the Council of Europe on 5 May 1949 (which is now Europe Day ). The Council of Europe was one of the first institutions to bring the sovereign states of (then only Western) Europe together, raising great hopes and fevered debates in the following two years for further European integration. It has since been
12512-573: The device is a significant risk device or is not in some way exempt from prior submission to the FDA. In addition, clinical research may require Institutional Review Board or Research Ethics Board and possibly other institutional committee reviews, Privacy Board, Conflict of Interest Committee, Radiation Safety Committee or Radioactive Drug Research Committee. In the European Union , the European Medicines Agency acts in
12648-553: The discipline began to take its modern shape. The English doctor John Haygarth demonstrated the importance of a control group for the correct identification of the placebo effect in his celebrated study of the ineffective remedy called Perkin's tractors . Further work in that direction was carried out by the eminent physician Sir William Gull, 1st Baronet in the 1860s. Frederick Akbar Mahomed (d. 1884), who worked at Guy's Hospital in London , made substantial contributions to
12784-504: The disease or condition. The benefits must outweigh the risks. For example, many drugs to treat cancer have severe side effects that would not be acceptable for an over-the-counter pain medication, yet the cancer drugs have been approved since they are used under a physician's care and are used for a life-threatening condition. In the US the elderly constitute 14% of the population, while they consume over one-third of drugs. People over 55 (or
12920-562: The document. The document is not a contract, as the participant can withdraw at any time without penalty. Informed consent is a legal process in which a recruit is instructed about key facts before deciding whether to participate. Researchers explain the details of the study in terms the subject can understand. The information is presented in the subject's native language. Generally, children cannot autonomously provide informed consent, but depending on their age and other factors, may be required to provide informed assent. In any clinical trial,
13056-412: The drug approval process is treated as a separate clinical trial . If the drug successfully passes through Phases I, II, and III, it will be approved by the national regulatory authority for use in the general population. Phase IV is post-approval studies. Phase I includes 20 to 100 healthy volunteers or individuals with the disease or condition. This study typically lasts several months and its purpose
13192-412: The effects and possible interactions of several independent factors. Of these, blocking and factorial design are seldom applied in clinical trials, because the experimental units are human subjects and there is typically only one independent intervention: the treatment. The British Medical Research Council officially recognized the importance of clinical trials from the 1930s. The council established
13328-499: The efficacy of the chemical streptomycin for curing pulmonary tuberculosis . The trial was both double-blind and placebo-controlled . The methodology of clinical trials was further developed by Sir Austin Bradford Hill , who had been involved in the streptomycin trials. From the 1920s, Hill applied statistics to medicine, attending the lectures of renowned mathematician Karl Pearson , among others. He became famous for
13464-456: The entire cabinet, the final say in accepting or rejecting a candidate submitted for a given portfolio by a member state, and oversees the commission's permanent civil service. After the President, the most prominent commissioner is the high representative of the union for foreign affairs and security policy, who is ex-officio a vice-president of the European Commission and is also chosen by
13600-464: The euro, followed by Cyprus and Malta in 2008, Slovakia in 2009, Estonia in 2011, Latvia in 2014, and Lithuania in 2015. On 1 December 2009, the Lisbon Treaty entered into force and reformed many aspects of the EU. In particular, it changed the legal structure of the European Union, merging the EU three pillars system into a single legal entity provisioned with a legal personality , created
13736-481: The eurozone. The European Court of Auditors (ECA) is the auditory branch of the European Union. It was established in 1975 in Luxembourg in order to improve EU financial management. It has 27 members (1 from each EU member-state) supported by approximately 800 civil servants. The European Personnel Selection Office (EPSO) is the EU's civil service recruitment body and operates its selection of candidates via generalist and specialist competitions. Each institution
13872-554: The fall of the Eastern Bloc , the former East Germany became part of the communities as part of a reunified Germany . The European Union was formally established when the Maastricht Treaty —whose main architects were Horst Köhler , Helmut Kohl and François Mitterrand —came into force on 1 November 1993. The treaty also gave the name European Community to the EEC, even if it was referred to as such before
14008-421: The first time they have worked together in a late-stage trial. Patients whose genomic profiles do not match any of the trial drugs receive a drug designed to stimulate the immune system to attack cancer. A clinical trial protocol is a document used to define and manage the trial. It is prepared by a panel of experts. All study investigators are expected to strictly observe the protocol. The protocol describes
14144-778: The institutions of the developing European community under the European Political Community , which was to include the also proposed European Defence Community , an alternative to West Germany joining NATO which was established in 1949 under the Truman Doctrine . In 1954 the Modified Brussels Treaty transformed the Western Union into the Western European Union (WEU). West Germany eventually joined both
14280-425: The interests of the EU as a whole rather than their home state. The leader of the 27 is the president of the European Commission (presently Ursula von der Leyen for 2019–2024, reelected for the 2024-2029 term), proposed by the European Council , following and taking into account the result of the European elections, and is then elected by the European Parliament. The President retains, as the leader responsible for
14416-468: The internal market; enact legislation in justice and home affairs; and maintain common policies on trade , agriculture , fisheries and regional development . Passport controls have been abolished for travel within the Schengen Area . The eurozone is a group composed of the 20 EU member states that have fully implemented the economic and monetary union and use the euro currency . Through
14552-418: The intervention's efficacy was generally lacking. For instance, Lady Mary Wortley Montagu , who campaigned for the introduction of inoculation (then called variolation) to prevent smallpox , arranged for seven prisoners who had been sentenced to death to undergo variolation in exchange for their life. Although they survived and did not contract smallpox, there was no control group to assess whether this result
14688-534: The legal inception of the European Union (EU)—the principal framework for this unification. The EU inherited many of its present responsibilities from the European Communities (EC), which were founded in the 1950s in the spirit of the Schuman Declaration . The European Union operates through a hybrid system of supranational and intergovernmental decision-making, and according to
14824-486: The member states can only legislate to the extent to which the EU has not. In other policy areas, the EU can only co-ordinate, support and supplement member state action but cannot enact legislation with the aim of harmonising national laws. That a particular policy area falls into a certain category of competence is not necessarily indicative of what legislative procedure is used for enacting legislation within that policy area. Different legislative procedures are used within
14960-507: The member states. Since then, the eurozone has increased to encompass 20 countries. The euro currency became the second-largest reserve currency in the world. In 2004, the EU saw its biggest enlargement to date when Cyprus, the Czech Republic, Estonia , Hungary , Latvia , Lithuania , Malta , Poland , Slovakia , and Slovenia joined the union. In 2007, Bulgaria and Romania became EU members. Later that year, Slovenia adopted
15096-410: The national regulatory authority for use in the general population. Phase IV trials are performed after the newly approved drug, diagnostic or device is marketed, providing assessment about risks, benefits, or best uses. A fundamental distinction in evidence-based practice is between observational studies and randomized controlled trials . Types of observational studies in epidemiology , such as
15232-420: The necessity for national implementation measures (regulations) and those which specifically require national implementation measures (directives). EU policy is in general promulgated by EU directives , which are then implemented in the domestic legislation of its member states , and EU regulations , which are immediately enforceable in all member states. Lobbying at the EU level by special interest groups
15368-408: The number of subjects, also called the sample size, has a large impact on the ability to reliably detect and measure the effects of the intervention. This ability is described as its " power ", which must be calculated before initiating a study to figure out if the study is worth its costs. In general, a larger sample size increases the statistical power, also the cost. The statistical power estimates
15504-549: The origin of the main institutions of the EU such as the European Commission and Parliament . Founding fathers of the European Union understood that coal and steel were the two industries essential for waging war, and believed that by tying their national industries together, a future war between their nations became much less likely. In parallel with Schuman, the Pleven Plan of 1951 tried but failed to tie
15640-606: The process of clinical trials, where "he separated chronic nephritis with secondary hypertension from what we now term essential hypertension . He also founded the Collective Investigation Record for the British Medical Association ; this organization collected data from physicians practicing outside the hospital setting and was the precursor of modern collaborative clinical trials." Ideas of Sir Ronald A. Fisher still play
15776-407: The research more grounded in the needs of the specific communities they are part of. Public contributors can also ensure that the research is presented in plain language that is clear to the wider society and the specific groups it is most relevant for. Although early medical experimentation was performed often, the use of a control group to provide an accurate comparison for the demonstration of
15912-418: The safety and relative effectiveness of a medication or device: While most clinical trials test one alternative to the novel intervention, some expand to three or four and may include a placebo . Except for small, single-location trials, the design and objectives are specified in a document called a clinical trial protocol . The protocol is the trial's "operating manual" and ensures all researchers perform
16048-478: The same category of competence, and even with the same policy area. The distribution of competences in various policy areas between member states and the union is divided into the following three categories: The European Union has seven principal decision-making bodies, its institutions : the European Parliament , the European Council , the Council of the European Union , the European Commission ,
16184-553: The same courts and the Common Assembly. The EEC was headed by Walter Hallstein ( Hallstein Commission ) and Euratom was headed by Louis Armand ( Armand Commission ) and then Étienne Hirsch ( Hirsch Commission ). The OEEC was in turn reformed in 1961 into the Organisation for Economic Co-operation and Development (OECD) and its membership was extended to states outside of Europe, the United States and Canada. During
16320-494: The scientific rationale, objective(s), design, methodology, statistical considerations and organization of the planned trial. Details of the trial are provided in documents referenced in the protocol, such as an investigator's brochure . The protocol contains a precise study plan to assure safety and health of the trial subjects and to provide an exact template for trial conduct by investigators. This allows data to be combined across all investigators/sites. The protocol also informs
16456-449: The several peoples of the separate member states, rather than from a single undifferentiated whole. This is reflected in the fact that the member states remain the 'masters of the Treaties', retaining control over the allocation of competences to the union through constitutional change (thus retaining so-called Kompetenz-kompetenz ); in that they retain control of the use of armed force; they retain control of taxation; and in that they retain
16592-564: The study administrators (often a contract research organization ). The format and content of clinical trial protocols sponsored by pharmaceutical, biotechnology or medical device companies in the United States, European Union, or Japan have been standardized to follow Good Clinical Practice guidance issued by the International Conference on Harmonisation (ICH). Regulatory authorities in Canada , China , South Korea , and
16728-832: The study treatment causes an effect on human health. Some Phase II and most Phase III drug trials are designed as randomized, double-blind , and placebo -controlled. Clinical studies having small numbers of subjects may be "sponsored" by single researchers or a small group of researchers, and are designed to test simple questions or feasibility to expand the research for a more comprehensive randomized controlled trial. Clinical studies can be "sponsored" (financed and organized) by academic institutions, pharmaceutical companies, government entities and even private groups. Trials are conducted for new drugs, biotechnology, diagnostic assays or medical devices to determine their safety and efficacy prior to being submitted for regulatory review that would determine market approval. In cases where giving
16864-456: The subject of derision. Clinical trials are classified by the research objective created by the investigators. Trials are classified by their purpose. After approval for human research is granted to the trial sponsor, the U.S. Food and Drug Administration (FDA) organizes and monitors the results of trials according to type: Clinical trials are conducted typically in four phases, with each phase using different numbers of subjects and having
17000-430: The subjects' health for a defined time period. Data include measurements such as vital signs , concentration of the study drug in the blood or tissues, changes to symptoms, and whether improvement or worsening of the condition targeted by the study drug occurs. The researchers send the data to the trial sponsor, who then analyzes the pooled data using statistical tests . Examples of clinical trial goals include assessing
17136-443: The surgical setting, case-controlled studies will be replaced. Besides being participants in a clinical trial, members of the public can be actively collaborate with researchers in designing and conducting clinical research . This is known as patient and public involvement (PPI). Public involvement involves a working partnership between patients, caregivers, people with lived experience, and researchers to shape and influence what
17272-407: The test article (including its safety toxicity if applicable and efficacy , if possible at this early stage) are studied. The clinical research ecosystem involves a complex network of sites, pharmaceutical companies and academic research institutions. Clinical research is often conducted at academic medical centers and affiliated research study sites. These centers and sites provide the prestige of
17408-546: The treatment of abdominal aortic aneurysm , which compared the older open aortic repair technique to the newer endovascular aneurysm repair device. An example of the latter are clinical trials on mechanical devices used in the management of adult female urinary incontinence . Similarly to drugs, medical or surgical procedures may be subjected to clinical trials, such as comparing different surgical approaches in treatment of fibroids for subfertility . However, when clinical trials are unethical or logistically impossible in
17544-505: The treaty. With further enlargement planned to include the former communist states of Central and Eastern Europe, as well as Cyprus and Malta , the Copenhagen criteria for candidate members to join the EU were agreed upon in June 1993. The expansion of the EU introduced a new level of complexity and discord. In 1995, Austria, Finland, and Sweden joined the EU. In 2002, euro banknotes and coins replaced national currencies in 12 of
17680-501: The trial in the same way on similar subjects and that the data is comparable across all subjects. As a trial is designed to test hypotheses and rigorously monitor and assess outcomes, it can be seen as an application of the scientific method , specifically the experimental step. The most common clinical trials evaluate new pharmaceutical products, medical devices, biologics , diagnostic assays , psychological therapies , or other interventions. Clinical trials may be required before
17816-516: The trial, such as monitoring and lab work, may be managed by an outsourced partner, such as a contract research organization or a central laboratory. Only 10 percent of all drugs started in human clinical trials become approved drugs . Some clinical trials involve healthy subjects with no pre-existing medical conditions . Other clinical trials pertain to people with specific health conditions who are willing to try an experimental treatment. Pilot experiments are conducted to gain insights for design of
17952-487: The union for foreign affairs and security policy (presently Josep Borrell ) also takes part in its meetings. Described by some as the union's "supreme political leadership", it is actively involved in the negotiation of treaty changes and defines the EU's policy agenda and strategies. Its leadership role involves solving disputes between member states and the institutions, and to resolving any political crises or disagreements over controversial issues and policies. It acts as
18088-481: Was due to the inoculation or some other factor. Similar experiments performed by Edward Jenner over his smallpox vaccine were equally conceptually flawed. The first proper clinical trial was conducted by the Scottish physician James Lind . The disease scurvy , now known to be caused by a Vitamin C deficiency, would often have terrible effects on the welfare of the crew of long-distance ocean voyages. In 1740,
18224-476: Was established, along with its citizenship , when the Maastricht Treaty came into force in 1993, and was incorporated as an international legal juridical person upon entry into force of the Treaty of Lisbon in 2009 . Its beginnings can be traced to the Inner Six states (Belgium, France, Italy, Luxembourg, the Netherlands, and West Germany ) at the start of modern European integration in 1948, and to
18360-474: Was spent on transport , building and the environment, €16bn on education and research , €13bn on welfare, €20bn on foreign and defence policy, €2bn in finance , €2bn in energy , €1.5bn in communications, and €13bn in administration. In November 2020, two members of the union, Hungary and Poland, blocked approval to the EU's budget at a meeting in the Committee of Permanent Representatives (Coreper), citing
18496-475: Was the signing of the Treaty of Dunkirk between France and the United Kingdom . The treaty assured mutual assistance in the event of future military aggression against either nation. Though it officially named Germany as a threat, in reality the actual concern was for the Soviet Union. A few days later came the announcement of the Truman Doctrine which pledged American support for democracies to counter
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