romikgosai/squad_modified huggingface dataset:
Drug discovery and development is very expensive; of all compounds investigated for use in humans only a small fraction are eventually approved in most nations by government appointed medical institutions or boards, who have to approve new drugs before they can be marketed in those countries. In 2010 18 NMEs (New Molecular Entities) were approved and three biologics by the FDA, or 21 in total, which is down from 26 in 2009 and 24 in 2008. On the other hand, there were only 18 approvals in total in 2007 and 22 back in 2006. Since 2001, the Center for Drug Evaluation and Research has averaged 22.9 approvals a year. This approval comes only after heavy investment in pre-clinical development and clinical trials, as well as a commitment to ongoing safety monitoring. Drugs which fail part-way through this process often incur large costs, while generating no revenue in return. If the cost of these failed drugs is taken into account, the cost of developing a successful new drug (new chemical entity, or NCE), has been estimated at about 1.3 billion USD(not including marketing expenses). Professors Light and Lexchin reported in 2012, however, that the rate of approval for new drugs has been a relatively stable average rate of 15 to 25 for decades.

Questions and answers:
['
Q: How much does it cost to develop a new drug?
A: about 1.3 billion', '
Q: How many approvals of new drugs happen every year?
A: averaged 22.9 approvals', '
Q: Who is responsible for approval or rejection of new drugs?
A: Center for Drug Evaluation and Research', '
Q: How many drugs were approved in 2007?
A: 18 approvals', '
Q: Who reported the stable average rate in 2012?
A: Professors Light and Lexchin', '
Q: What does NMEs stand for?
A: New Molecular Entities', '
Q: How many pharmaceutical drugs were approved on average since 2001?
A: 22.9', '
Q: What is the approximate cost of developing a new drug, including the costs of failure?
A: 1.3 billion USD', '
Q: What has been the stable approval rate of new drugs?
A: 15 to 25']
Some of these estimates also take into account the opportunity cost of investing capital many years before revenues are realized (see Time-value of money). Because of the very long time needed for discovery, development, and approval of pharmaceuticals, these costs can accumulate to nearly half the total expense. A direct consequence within the pharmaceutical industry value chain is that major pharmaceutical multinationals tend to increasingly outsource risks related to fundamental research, which somewhat reshapes the industry ecosystem with biotechnology companies playing an increasingly important role, and overall strategies being redefined accordingly. Some approved drugs, such as those based on re-formulation of an existing active ingredient (also referred to as Line-extensions) are much less expensive to develop.

Questions and answers:
['
Q: What drugs are the least expensive to develop?
A: those based on re-formulation of an existing active ingredient', '
Q: What accounts for nearly half of the costs to develop drugs?
A: opportunity cost of investing capital', '
Q: What is the consequence in the value chain?
A: increasingly outsource risks related to fundamental research', '
Q: What happens when companies outsource?
A: somewhat reshapes the industry ecosystem with biotechnology companies', '
Q: What is re-formulations of active ingredients referred to?
A: Line-extensions', '
Q: Investing capital can increase drug development costs by how much?
A: nearly half the total expense', '
Q: What kind of companies have had a more important role in drug development?
A: biotechnology', '
Q: What firms tend to outsource drug development?
A: major pharmaceutical multinationals']
In 1971, Akira Endo, a Japanese biochemist working for the pharmaceutical company Sankyo, identified mevastatin (ML-236B), a molecule produced by the fungus Penicillium citrinum, as an inhibitor of HMG-CoA reductase, a critical enzyme used by the body to produce cholesterol. Animal trials showed very good inhibitory effect as in clinical trials, however a long term study in dogs found toxic effects at higher doses and as a result mevastatin was believed to be too toxic for human use. Mevastatin was never marketed, because of its adverse effects of tumors, muscle deterioration, and sometimes death in laboratory dogs.

Questions and answers:
['
Q: Why was Mevastatin never marketed?
A: adverse effects of tumors, muscle deterioration, and sometimes death', '
Q: Who discovered Mevastatin?
A: Akira Endo', '
Q: What is HMG-CoA responsible for producing?
A: cholesterol', '
Q: Where did Endo discover ML-236B?
A: Penicillium citrinum', '
Q: What was discovered in long term studies?
A: too toxic for human use', '
Q: In what year was mevastatin discovered?
A: 1971', '
Q: Who discovered mevastatin?
A: Akira Endo', '
Q: What organism produces mevastatin?
A: Penicillium citrinum', '
Q: What enzyme helps produce cholesterol?
A: HMG-CoA reductase']
Every major company selling the antipsychotics — Bristol-Myers Squibb, Eli Lilly, Pfizer, AstraZeneca and Johnson & Johnson — has either settled recent government cases, under the False Claims Act, for hundreds of millions of dollars or is currently under investigation for possible health care fraud. Following charges of illegal marketing, two of the settlements set records last year for the largest criminal fines ever imposed on corporations. One involved Eli Lilly's antipsychotic Zyprexa, and the other involved Bextra. In the Bextra case, the government also charged Pfizer with illegally marketing another antipsychotic, Geodon; Pfizer settled that part of the claim for $301 million, without admitting any wrongdoing.

Questions and answers:
['
Q: How much did Pfizer settle the illegal marketing suit for?
A: $301 million', '
Q: What drugs were involved in cases of the largest criminal fines?
A: Zyprexa, and the other involved Bextra', '
Q: What was Pfizer accused of illegally marketing?
A: Geodon', '
Q: What companies have been involved with health care fraud cases?
A: Bristol-Myers Squibb, Eli Lilly, Pfizer, AstraZeneca and Johnson & Johnson', '
Q: What do illegal marketing cases fall under?
A: False Claims Act', '
Q: Firms such as Eli Lilly, Pfizer, and AstraZeneca have settled claims under what act?
A: False Claims Act', '
Q: Zyprexa was owned by what company?
A: Eli Lilly', '
Q: Pfizer was charged with illegally marketing what antipsychotic drug?
A: Geodon', '
Q: Pfizer settled the Geodon lawsuit for how much money?
A: $301 million']
In contrast to this viewpoint, an article and associated editorial in the New England Journal of Medicine in May 2015 emphasized the importance of pharmaceutical industry-physician interactions for the development of novel treatments, and argued that moral outrage over industry malfeasance had unjustifiably led many to overemphasize the problems created by financial conflicts of interest. The article noted that major healthcare organizations such as National Center for Advancing Translational Sciences of the National Institutes of Health, the President’s Council of Advisors on Science and Technology, the World Economic Forum, the Gates Foundation, the Wellcome Trust, and the Food and Drug Administration had encouraged greater interactions between physicians and industry in order to bring greater benefits to patients.

Questions and answers:
['
Q: Who were some of the companies that encouraged the interactions between doctors and the pharmaceutical industry?
A: World Economic Forum, the Gates Foundation, the Wellcome Trust, and the Food and Drug Administration', '
Q: When did the article come out about the importance of interactions?
A: May 2015', '
Q: What was the reason behind these interactions?
A: bring greater benefits to patients', '
Q: What was believed to have created a financial conflict of interest?
A: moral outrage over industry malfeasance', '
Q: Who printed the article about the importance of interactions?
A: New England Journal of Medicine', '
Q: What publication had an article about the importance of pharmaceutical industry-physician interactions in 2015?
A: New England Journal of Medicine', '
Q: When was the editorial published?
A: May 2015', '
Q: Did major healthcare organizations support or discourage interactions between doctors and industries?
A: encouraged greater interactions']
An investigation by ProPublica found that at least 21 doctors have been paid more than $500,000 for speeches and consulting by drugs manufacturers since 2009, with half of the top earners working in psychiatry, and about $2 billion in total paid to doctors for such services. AstraZeneca, Johnson & Johnson and Eli Lilly have paid billions of dollars in federal settlements over allegations that they paid doctors to promote drugs for unapproved uses. Some prominent medical schools have since tightened rules on faculty acceptance of such payments by drug companies.

Questions and answers:
['
Q: Who conduced an investigation on doctors?
A: ProPublica', '
Q: Billions of dollars have been paid by which companies?
A: AstraZeneca, Johnson & Johnson and Eli Lilly', '
Q: How much was discovered to have been paid to doctors by drug companies?
A: more than $500,000', '
Q: What was the reason these companies have to pay fines?
A: allegations that they paid doctors to promote drugs for unapproved uses', '
Q: How many doctors have been paid by varies companies?
A: at least 21', '
Q: A ProPublica study found that some doctors were being paid how much money for speeches?
A: more than $500,000', '
Q: Half of the top earners were mostly in what field?
A: psychiatry', '
Q: Drug manufacturers paid off doctors a total of how much money?
A: $2 billion']
Often, large multinational corporations exhibit vertical integration, participating in a broad range of drug discovery and development, manufacturing and quality control, marketing, sales, and distribution. Smaller organizations, on the other hand, often focus on a specific aspect such as discovering drug candidates or developing formulations. Often, collaborative agreements between research organizations and large pharmaceutical companies are formed to explore the potential of new drug substances. More recently, multi-nationals are increasingly relying on contract research organizations to manage drug development.

Questions and answers:
['
Q: Why are collaborative agreements important?
A: to explore the potential of new drug substances', '
Q: How do large corporations show vertical integration?
A: participating in a broad range of drug discovery and development, manufacturing and quality control, marketing, sales, and distribution', '
Q: What are large companies relying on outside organizations for?
A: to manage drug development', '
Q: What are smaller organizations responsible for?
A: focus on a specific aspect such as discovering drug candidates or developing formulations', '
Q: What type of integration do large corporations often do?
A: vertical', '
Q: What type of integration do smaller organizations do?
A: a specific aspect', '
Q: What type of agreements are made to research potential new drugs?
A: collaborative agreements', '
Q: What type of organizations are multinational corporations increasingly rely on?
A: contract research']
In the UK, the Medicines and Healthcare Products Regulatory Agency approves drugs for use, though the evaluation is done by the European Medicines Agency, an agency of the European Union based in London. Normally an approval in the UK and other European countries comes later than one in the USA. Then it is the National Institute for Health and Care Excellence (NICE), for England and Wales, who decides if and how the National Health Service (NHS) will allow (in the sense of paying for) their use. The British National Formulary is the core guide for pharmacists and clinicians.

Questions and answers:
['
Q: Who is the core guide?
A: The British National Formulary', '
Q: Who is responsible for approving drugs in the United Kingdom?
A: Medicines and Healthcare Products Regulatory Agency', '
Q: After an approval in the United States, when does an approval occur in the United Kingdom and other countries?
A: comes later', '
Q: Who decides how NHS will allow drugs?
A: National Institute for Health and Care Excellence (NICE)', '
Q: Who does the evaluations for drugs in the United Kingdom?
A: European Medicines Agency', '
Q: What UK firm approves pharmaceutical drugs?
A: Medicines and Healthcare Products Regulatory Agency', '
Q: What UK organization evaluates drugs? 
A: European Medicines Agency', '
Q: What firm in England and Wales decides if the NHS allows drugs?
A: National Institute for Health and Care Excellence', '
Q: What is the name of the core guide for pharmacists and clinicians?
A: British National Formulary']
There are special rules for certain rare diseases ("orphan diseases") in several major drug regulatory territories. For example, diseases involving fewer than 200,000 patients in the United States, or larger populations in certain circumstances are subject to the Orphan Drug Act.  Because medical research and development of drugs to treat such diseases is financially disadvantageous, companies that do so are rewarded with tax reductions, fee waivers, and market exclusivity on that drug for a limited time (seven years), regardless of whether the drug is protected by patents.

Questions and answers:
['
Q: What is subject to the Orphan Drug Act?
A: diseases involving fewer than 200,000 patients in the United States, or larger populations in certain circumstances', '
Q: What is given to companies who develop drugs for "orphan diseases"?
A: tax reductions, fee waivers, and market exclusivity on that drug for a limited time (seven years), regardless of whether the drug is protected by patents', '
Q: Why are these companies rewarded?
A: Because medical research and development of drugs to treat such diseases is financially disadvantageous', '
Q: What size of disease populations are subject to the Orphan Drug Act?
A: fewer than 200,000 patients', '
Q: What is one financial benefit to researching orphan drugs?
A: tax reductions', '
Q: What is the length of time of market exclusivity of an orphan drug?
A: seven years', '
Q: What is a term for rare diseases in some territories?
A: orphan diseases']
Ben Goldacre has argued that regulators – such as the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK, or the Food and Drug Administration (FDA) in the United States – advance the interests of the drug companies rather than the interests of the public due to revolving door exchange of employees between the regulator and the companies and friendships develop between regulator and company employees. He argues that regulators do not require that new drugs offer an improvement over what is already available, or even that they be particularly effective.

Questions and answers:
['
Q: Who argued against regulators?
A: Ben Goldacre', '
Q: Who argued that drug regulators were greater serving the interests of the drug companies than the patients?
A: Ben Goldacre', '
Q: The business friendships between which parties have been criticized?
A: regulator and company employees', "
Q: Goldacre argued that which party didn't require that new drugs be improved at all?
A: regulators"]
In many non-US western countries a 'fourth hurdle' of cost effectiveness analysis has developed before new technologies can be provided. This focuses on the efficiency (in terms of the cost per QALY) of the technologies in question rather than their efficacy. In England and Wales NICE decides whether and in what circumstances drugs and technologies will be made available by the NHS, whilst similar arrangements exist with the Scottish Medicines Consortium in Scotland, and the Pharmaceutical Benefits Advisory Committee in Australia. A product must pass the threshold for cost-effectiveness if it is to be approved. Treatments must represent 'value for money' and a net benefit to society.

Questions and answers:
['
Q: NICE decides the availability of drugs in which two countries?
A: England and Wales', '
Q: What is the name of the organization in Scotland that decides the availability of drugs?
A: Scottish Medicines Consortium', '
Q: What threshold must a drug pass before it is approved?
A: cost-effectiveness']
The top ten best-selling drugs of 2013 totaled $75.6 billion in sales, with the anti-inflammatory drug Humira being the best-selling drug worldwide at $10.7 billion in sales. The second and third best selling were Enbrel and Remicade, respectively. The top three best-selling drugs in the United States in 2013 were Abilify ($6.3 billion,) Nexium ($6 billion) and Humira ($5.4 billion). The best-selling drug ever, Lipitor, averaged $13 billion annually and netted $141 billion total over its lifetime before Pfizer's patent expired in November 2011.

Questions and answers:
['
Q: How much money did the top ten bestselling drugs make in 2013?
A: $75.6 billion', '
Q: What was the name of the top-selling anti-inflammatory drug in 2013?
A: Humira', '
Q: What was the bestselling drug in history?
A: Lipitor', '
Q: How much money did Lipitor make before the patent expired?
A: $141 billion', "
Q: In what year did Pfizer's patent over Lipitor expire?
A: 2011"]
Depending on a number of considerations, a company may apply for and be granted a patent for the drug, or the process of producing the drug, granting exclusivity rights typically for about 20 years. However, only after rigorous study and testing, which takes 10 to 15 years on average, will governmental authorities grant permission for the company to market and sell the drug. Patent protection enables the owner of the patent to recover the costs of research and development through high profit margins for the branded drug. When the patent protection for the drug expires, a generic drug is usually developed and sold by a competing company. The development and approval of generics is less expensive, allowing them to be sold at a lower price. Often the owner of the branded drug will introduce a generic version before the patent expires in order to get a head start in the generic market. Restructuring has therefore become routine, driven by the patent expiration of products launched during the industry's "golden era" in the 1990s and companies' failure to develop sufficient new blockbuster products to replace lost revenues.

Questions and answers:
['
Q: How long do drug exclusivity rights usually last?
A: 20 years', '
Q: Governments grant permission to market drugs after how many years?
A: 10 to 15 years on average', "
Q: What enables a drug's owner to recover R&D costs?
A: Patent protection", '
Q: What kind of drug is produced by competitors once a patent expires?
A: generic', '
Q: What decade was the pharmaceutical industry\'s "golden era"?
A: 1990s']
In the United States, new pharmaceutical products must be approved by the Food and Drug Administration (FDA) as being both safe and effective. This process generally involves submission of an Investigational New Drug filing with sufficient pre-clinical data to support proceeding with human trials. Following IND approval, three phases of progressively larger human clinical trials may be conducted. Phase I generally studies toxicity using healthy volunteers. Phase II can include pharmacokinetics and dosing in patients, and Phase III is a very large study of efficacy in the intended patient population. Following the successful completion of phase III testing, a New Drug Application is submitted to the FDA. The FDA review the data and if the product is seen as having a positive benefit-risk assessment, approval to market the product in the US is granted.

Questions and answers:
['
Q: The safety and efficacy of new drugs must be approved by what organization in the US?
A: Food and Drug Administration', '
Q: What type of filing is used before beginning human trials?
A: Investigational New Drug', '
Q: How many phases of human trials may be done after IND approval?
A: three', '
Q: What type of application is filed after completing three phases of human trials?
A: New Drug Application', '
Q: What type of risk assessment results in approving the drug to go on the market?
A: positive benefit-risk']
Advertising is common in healthcare journals as well as through more mainstream media routes. In some countries, notably the US, they are allowed to advertise directly to the general public. Pharmaceutical companies generally employ sales people (often called 'drug reps' or, an older term, 'detail men') to market directly and personally to physicians and other healthcare providers. In some countries, notably the US, pharmaceutical companies also employ lobbyists to influence politicians. Marketing of prescription drugs in the US is regulated by the federal Prescription Drug Marketing Act of 1987.

Questions and answers:
['
Q: "Drug reps" are usually hired by what type of firms?
A: Pharmaceutical companies', '
Q: What law regulates drug marketing in the US?
A: Prescription Drug Marketing Act of 1987', '
Q: Who do drug reps market to?
A: directly and personally to physicians']
There has been increasing controversy surrounding pharmaceutical marketing and influence. There have been accusations and findings of influence on doctors and other health professionals through drug reps, including the constant provision of marketing 'gifts' and biased information to health professionals; highly prevalent advertising in journals and conferences; funding independent healthcare organizations and health promotion campaigns; lobbying physicians and politicians (more than any other industry in the US); sponsorship of medical schools or nurse training; sponsorship of continuing educational events, with influence on the curriculum; and hiring physicians as paid consultants on medical advisory boards.

Questions and answers:
["
Q: Drug reps have been accused of giving what to health professionals?
A: 'gifts' and biased information", '
Q: Drug marketers have hired who as paid consultants?
A: physicians', '
Q: What publications can drug ads be commonly found?
A: journals and conferences']
The rivalries between the Arab tribes had caused unrest in the provinces outside Syria, most notably in the Second Muslim Civil War of 680–692 CE and the Berber Revolt of 740–743 CE. During the Second Civil War, leadership of the Umayyad clan shifted from the Sufyanid branch of the family to the Marwanid branch. As the constant campaigning exhausted the resources and manpower of the state, the Umayyads, weakened by the Third Muslim Civil War of 744–747 CE, were finally toppled by the Abbasid Revolution in 750 CE/132 AH. A branch of the family fled across North Africa to Al-Andalus, where they established the Caliphate of Córdoba, which lasted until 1031 before falling due to the Fitna of al-Ándalus.

Questions and answers:
['
Q: In what year CE did the Second Muslim Civil War end?
A: 692', '
Q: During what period did the Berber Revolt occur?
A: 740–743 CE', '
Q: What branch took over Umayyad leadership during the Second Civil War?
A: Marwanid']
Ali was assassinated in 661 by a Kharijite partisan. Six months later in the same year, in the interest of peace, Hasan ibn Ali, highly regarded for his wisdom and as a peacemaker, and the Second Imam for the Shias, and the grandson of Muhammad, made a peace treaty with Muawiyah I. In the Hasan-Muawiya treaty, Hasan ibn Ali handed over power to Muawiya on the condition that he be just to the people and keep them safe and secure, and after his death he not establish a dynasty. This brought to an end the era of the Rightly Guided Caliphs for the Sunnis, and Hasan ibn Ali was also the last Imam for the Shias to be a Caliph. Following this, Mu'awiyah broke the conditions of the agreement and began the Umayyad dynasty, with its capital in Damascus.

Questions and answers:
['
Q: In what year was Ali killed?
A: 661', '
Q: Who killed Ali?
A: Kharijite partisan', '
Q: Who made peace with Muawiyah I?
A: Hasan ibn Ali', '
Q: Where was the capital of the Umayyad dynasty?
A: Damascus']