romikgosai/squad_modified_2 huggingface dataset:
The thalidomide tragedy resurrected Kefauver's bill to enhance drug regulation that had stalled in Congress, and the Kefauver-Harris Amendment became law on 10 October 1962. Manufacturers henceforth had to prove to FDA that their drugs were effective as well as safe before they could go on the US market. The FDA received authority to regulate advertising of prescription drugs and to establish good manufacturing practices. The law required that all drugs introduced between 1938 and 1962 had to be effective. An FDA - National Academy of Sciences collaborative study showed that nearly 40 percent of these products were not effective. A similarly comprehensive study of over-the-counter products began ten years later.

Q1: When did the Kefauver-Harris Amendment become a law?
A1: 10 October 1962
Q2: What did this new law require?
A2: all drugs introduced between 1938 and 1962 had to be effective
Q3: What did the National Academy of Science's study discover?
A3: nearly 40 percent of these products were not effective
Q4: How long after the National Academy of Science's study did a study on over the counter drugs occur?
A4: ten years later
Q5: What brought up enhancement of drug regulations?
A5: The thalidomide tragedy
Q6: When did the Kefauver-Harris Amendment became law?
A6: 10 October 1962
Q7: What federal agency regulated the advertising of prescription drugs?
A7: FDA
Q8: Drugs made between which years had to be tested before going to market?
A8: 1938 and 1962
Q9: What percentage of drugs were shown to be ineffective after an FDA study?
A9: 40 percent
The firm continued to pressure Kelsey and the agency to approve the application—until November 1961, when the drug was pulled off the German market because of its association with grave congenital abnormalities. Several thousand newborns in Europe and elsewhere suffered the teratogenic effects of thalidomide. Though the drug was never approved in the USA, the firm distributed Kevadon to over 1,000 physicians there under the guise of investigational use. Over 20,000 Americans received thalidomide in this "study," including 624 pregnant patients, and about 17 known newborns suffered the effects of the drug.[citation needed]

Q1: How many Americans were given the drug Kevadon?
A1: Over 20,000
Q2: When was the drug taken off shelves in Germany?
A2: November 1961
Q3: How many newborns were born with issues due to Kevadon?
A3: about 17
Q4: How was Kevadon distributed to doctors?
A4: under the guise of investigational use
Q5: Why was this drug pulled off shelves?
A5: association with grave congenital abnormalities
Q6: In what year was thalidomide banned in Germany?
A6: 1961
Q7: What adverse effect was thalidomide associated with?
A7: congenital abnormalities
Q8: Thalidomide was distributed in the USA by what name?
A8: Kevadon
Q9: About how many Americans received thalidomide in a supposed study?
A9: Over 20,000
Q10: How many newborn American babies were affected by thalidomide?
A10: 17
Prior to the second world war, birth control was prohibited in many countries, and in the United States even the discussion of contraceptive methods sometimes led to prosecution under Comstock laws. The history of the development of oral contraceptives is thus closely tied to the birth control movement and the efforts of activists Margaret Sanger, Mary Dennett, and Emma Goldman. Based on fundamental research performed by Gregory Pincus and synthetic methods for progesterone developed by Carl Djerassi at Syntex and by Frank Colton at G.D. Searle & Co., the first oral contraceptive, Enovid, was developed by E.D. Searle and Co. and approved by the FDA in 1960. The original formulation incorporated vastly excessive doses of hormones, and caused severe side effects. Nonetheless, by 1962, 1.2 million American women were on the pill, and by 1965 the number had increased to 6.5 million. The availability of a convenient form of temporary contraceptive led to dramatic changes in social mores including expanding the range of lifestyle options available to women, reducing the reliance of women on men for contraceptive practice, encouraging the delay of marriage, and increasing pre-marital co-habitation.

Q1: What law prohibited birth control?
A1: Comstock laws
Q2: When was Enovid first approved?
A2: 1960
Q3: What increased due to the availability of birth control?
A3: pre-marital co-habitation
Q4: Who created the first oral birth control?
A4: E.D. Searle and Co
Q5: In 1965, how many women were on the birth control pill?
A5: 6.5 million
Q6: Discussing contraception sometimes led to prosecution under what laws?
A6: Comstock laws
Q7: What was the name of the first oral contraceptive?
A7: Enovid
Q8: By 1965, about how many American women were taking Enovid?
A8: 6.5 million
Q9: When did the FDA approve Enovid?
A9: 1960
Q10: Birth control was prohibited in most countries before what war?
A10: second world war
In April 1994, the results of a Merck-sponsored study, the Scandinavian Simvastatin Survival Study, were announced. Researchers tested simvastatin, later sold by Merck as Zocor, on 4,444 patients with high cholesterol and heart disease. After five years, the study concluded the patients saw a 35% reduction in their cholesterol, and their chances of dying of a heart attack were reduced by 42%. In 1995, Zocor and Mevacor both made Merck over US$1 billion. Endo was awarded the 2006 Japan Prize, and the Lasker-DeBakey Clinical Medical Research Award in 2008. For his "pioneering research into a new class of molecules" for "lowering cholesterol,"[sentence fragment]

Q1: Who received the Laser-Debakey Clinical Medical Research Aware?
A1: Endo
Q2: How much money did Merk make in 1995?
A2: over US$1 billion
Q3: How many patients received Zocor?
A3: 4,444
Q4: What study did Merk sponsor in 1994?
A4: Scandinavian Simvastatin Survival Study
Q5: What did the study reveal after 5 years?
A5: a 35% reduction in their cholesterol, and their chances of dying of a heart attack were reduced by 42%
Q6: What was the brand name of simvastatin?
A6: Zocor
Q7: Patients treated with Zocor had their cholesterol reduced by how much?
A7: 35%
Q8: How much did Zocor reduce the chance of dying from a heart attack?
A8: 42%
Q9: How much money did Merck make from sales of Zocor and Mevacor?
A9: over US$1 billion
Q10: Endo received what award in 2008?
A10: Lasker-DeBakey Clinical Medical Research Award
Drug discovery is the process by which potential drugs are discovered or designed. In the past most drugs have been discovered either by isolating the active ingredient from traditional remedies or by serendipitous discovery. Modern biotechnology often focuses on understanding the metabolic pathways related to a disease state or pathogen, and manipulating these pathways using molecular biology or biochemistry. A great deal of early-stage drug discovery has traditionally been carried out by universities and research institutions.

Q1: What is a drug discovery?
A1: the process by which potential drugs are discovered or designed
Q2: Who is usually responsible for early stages of drug discovery?
A2: universities and research institutions
Q3: What is used to manipulate pathways?
A3: molecular biology or biochemistry
Q4: What is involved in drug discovery?
A4: isolating the active ingredient from traditional remedies or by serendipitous discovery
Q5: What focuses on metabolic pathways?
A5: biotechnology
Q6: What is the name of the process in which possible drugs are discovered?
A6: Drug discovery
Q7: What groups carry out most early drug discoveries?
A7: research institutions
Q8: What kind of technology studies the understanding and manipulation of disease states and pathogens?
A8: biotechnology
Q9: Most drugs have been found by isolating what from traditional remedies?
A9: active ingredient
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.

Q1: How much does it cost to develop a new drug?
A1: about 1.3 billion
Q2: How many approvals of new drugs happen every year?
A2: averaged 22.9 approvals
Q3: Who is responsible for approval or rejection of new drugs?
A3: Center for Drug Evaluation and Research
Q4: How many drugs were approved in 2007?
A4: 18 approvals
Q5: Who reported the stable average rate in 2012?
A5: Professors Light and Lexchin
Q6: What does NMEs stand for?
A6: New Molecular Entities
Q7: How many pharmaceutical drugs were approved on average since 2001?
A7: 22.9
Q8: What is the approximate cost of developing a new drug, including the costs of failure?
A8: 1.3 billion USD
Q9: What has been the stable approval rate of new drugs?
A9: 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.

Q1: What drugs are the least expensive to develop?
A1: those based on re-formulation of an existing active ingredient
Q2: What accounts for nearly half of the costs to develop drugs?
A2: opportunity cost of investing capital
Q3: What is the consequence in the value chain?
A3: increasingly outsource risks related to fundamental research
Q4: What happens when companies outsource?
A4: somewhat reshapes the industry ecosystem with biotechnology companies
Q5: What is re-formulations of active ingredients referred to?
A5: Line-extensions
Q6: Investing capital can increase drug development costs by how much?
A6: nearly half the total expense
Q7: What kind of companies have had a more important role in drug development?
A7: biotechnology
Q8: What firms tend to outsource drug development?
A8: 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.

Q1: Why was Mevastatin never marketed?
A1: adverse effects of tumors, muscle deterioration, and sometimes death
Q2: Who discovered Mevastatin?
A2: Akira Endo
Q3: What is HMG-CoA responsible for producing?
A3: cholesterol
Q4: Where did Endo discover ML-236B?
A4: Penicillium citrinum
Q5: What was discovered in long term studies?
A5: too toxic for human use
Q6: In what year was mevastatin discovered?
A6: 1971
Q7: Who discovered mevastatin?
A7: Akira Endo
Q8: What organism produces mevastatin?
A8: Penicillium citrinum
Q9: What enzyme helps produce cholesterol?
A9: 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.

Q1: How much did Pfizer settle the illegal marketing suit for?
A1: $301 million
Q2: What drugs were involved in cases of the largest criminal fines?
A2: Zyprexa, and the other involved Bextra
Q3: What was Pfizer accused of illegally marketing?
A3: Geodon
Q4: What companies have been involved with health care fraud cases?
A4: Bristol-Myers Squibb, Eli Lilly, Pfizer, AstraZeneca and Johnson & Johnson
Q5: What do illegal marketing cases fall under?
A5: False Claims Act
Q6: Firms such as Eli Lilly, Pfizer, and AstraZeneca have settled claims under what act?
A6: False Claims Act
Q7: Zyprexa was owned by what company?
A7: Eli Lilly
Q8: Pfizer was charged with illegally marketing what antipsychotic drug?
A8: Geodon
Q9: Pfizer settled the Geodon lawsuit for how much money?
A9: $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.

Q1: Who were some of the companies that encouraged the interactions between doctors and the pharmaceutical industry?
A1: World Economic Forum, the Gates Foundation, the Wellcome Trust, and the Food and Drug Administration
Q2: When did the article come out about the importance of interactions?
A2: May 2015
Q3: What was the reason behind these interactions?
A3: bring greater benefits to patients
Q4: What was believed to have created a financial conflict of interest?
A4: moral outrage over industry malfeasance
Q5: Who printed the article about the importance of interactions?
A5: New England Journal of Medicine
Q6: What publication had an article about the importance of pharmaceutical industry-physician interactions in 2015?
A6: New England Journal of Medicine
Q7: When was the editorial published?
A7: May 2015
Q8: Did major healthcare organizations support or discourage interactions between doctors and industries?
A8: 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.

Q1: Who conduced an investigation on doctors?
A1: ProPublica
Q2: Billions of dollars have been paid by which companies?
A2: AstraZeneca, Johnson & Johnson and Eli Lilly
Q3: How much was discovered to have been paid to doctors by drug companies?
A3: more than $500,000
Q4: What was the reason these companies have to pay fines?
A4: allegations that they paid doctors to promote drugs for unapproved uses
Q5: How many doctors have been paid by varies companies?
A5: at least 21
Q6: A ProPublica study found that some doctors were being paid how much money for speeches?
A6: more than $500,000
Q7: Half of the top earners were mostly in what field?
A7: psychiatry
Q8: Drug manufacturers paid off doctors a total of how much money?
A8: $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.

Q1: Why are collaborative agreements important?
A1: to explore the potential of new drug substances
Q2: How do large corporations show vertical integration?
A2: participating in a broad range of drug discovery and development, manufacturing and quality control, marketing, sales, and distribution
Q3: What are large companies relying on outside organizations for?
A3: to manage drug development
Q4: What are smaller organizations responsible for?
A4: focus on a specific aspect such as discovering drug candidates or developing formulations
Q5: What type of integration do large corporations often do?
A5: vertical
Q6: What type of integration do smaller organizations do?
A6: a specific aspect
Q7: What type of agreements are made to research potential new drugs?
A7: collaborative agreements
Q8: What type of organizations are multinational corporations increasingly rely on?
A8: 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.

Q1: Who is the core guide?
A1: The British National Formulary
Q2: Who is responsible for approving drugs in the United Kingdom?
A2: Medicines and Healthcare Products Regulatory Agency
Q3: After an approval in the United States, when does an approval occur in the United Kingdom and other countries?
A3: comes later
Q4: Who decides how NHS will allow drugs?
A4: National Institute for Health and Care Excellence (NICE)
Q5: Who does the evaluations for drugs in the United Kingdom?
A5: European Medicines Agency
Q6: What UK firm approves pharmaceutical drugs?
A6: Medicines and Healthcare Products Regulatory Agency
Q7: What UK organization evaluates drugs?
A7: European Medicines Agency
Q8: What firm in England and Wales decides if the NHS allows drugs?
A8: National Institute for Health and Care Excellence
Q9: What is the name of the core guide for pharmacists and clinicians?
A9: 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.

Q1: What is subject to the Orphan Drug Act?
A1: diseases involving fewer than 200,000 patients in the United States, or larger populations in certain circumstances
Q2: What is given to companies who develop drugs for "orphan diseases"?
A2: 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
Q3: Why are these companies rewarded?
A3: Because medical research and development of drugs to treat such diseases is financially disadvantageous
Q4: What size of disease populations are subject to the Orphan Drug Act?
A4: fewer than 200,000 patients
Q5: What is one financial benefit to researching orphan drugs?
A5: tax reductions
Q6: What is the length of time of market exclusivity of an orphan drug?
A6: seven years
Q7: What is a term for rare diseases in some territories?
A7: 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.

Q1: Who argued against regulators?
A1: Ben Goldacre
Q2: Who argued that drug regulators were greater serving the interests of the drug companies than the patients?
A2: Ben Goldacre
Q3: The business friendships between which parties have been criticized?
A3: regulator and company employees
Q4: Goldacre argued that which party didn't require that new drugs be improved at all?
A4: 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.

Q1: NICE decides the availability of drugs in which two countries?
A1: England and Wales
Q2: What is the name of the organization in Scotland that decides the availability of drugs?
A2: Scottish Medicines Consortium
Q3: What threshold must a drug pass before it is approved?
A3: cost-effectiveness