Sunday, January 26, 2020

Significance of Pharmacovigilance for Drug Safety

Significance of Pharmacovigilance for Drug Safety AIM: To present an overview on the pharmacovigilance practice and realize the significance of pharmacovigilance in envisaging drug safety and efficacy To decisively appraise the pharmacovigilance findings of the anti-diabetic drug Avandia INTRODUCTION AND BACKGROUND INFORMATION: The World Health Organization defines pharmacovigilance as â€Å"The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem†.9 THE NEED FOR PHARMACOVIGILANCE: Primarily let us understand the need for pharmacovigilance. It has been long debated that the data from animal experiments is not completely worth of extrapolation. The differences in their metabolic pathways, resistance to drugs and various other factors, the pharmacokinetics and dynamics of drugs tend to vary within species to species as well. Extrapolating such statistics from animals to humans though necessary is not foolproof. Additionally, the clinical trial environment is extremely controlled. The patient population, however large, is not a good representative of the general global population. The number of patients is limited. Owing to these facts, an adverse effect, which would occur in one in ten thousand or so, is very unlikely to arise within the restrictions of the clinical trial atmosphere. Moreover, in a real life situation the patients using the drug are likely to have other diseases, consuming other drugs and with different genetic make-ups. Accordingly arises the urgent need for better pharmacovigilance practices. The importance of identifying rare and serious adverse effects of drugs that have remained secret during the course of the clinical trial cannot be ignored. THE STEPS IN PHARMACOVIGILANCE: Spontaneous reporting and prescription event monitoring: Spontaneous reports and prescription event monitoring include reports of adverse effects of drugs to sponsors, CROs or regulatory authorities, reported by patients, nurses, doctors and other healthcare professionals and consumers. The above process is streamlined with the help of global and countrywide structured programs to accelerate the practice and facilitate consumers to testify an adverse effect. Example: the National Pharmacovigilance Program in India. All events that are serious (as defined in ICH-GCP), unexpected, unlabeled, additional efficacy and lack of efficacy should be promptly reported. An incoming report is called as a case report. FDA has defined certain characteristics of a good case report. They are as follows: â€Å"1. Description of the adverse events or disease experience, including time to onset of signs or symptoms; 2. Suspected and concomitant product therapy details (i.e., dose, lot number, schedule, dates, duration), including over-the-counter medications, dietary supplements, and recently discontinued medications; 3. Patient characteristics, including demographic information (e.g., age, race, sex), baseline medical condition prior to product therapy, co-morbid conditions, use of concomitant medications, relevant family history of disease, and presence of other risk factors; 4. Documentation of the diagnosis of the events, including methods used to make the diagnosis; 5. Clinical course of the event and patient outcomes (e.g., hospitalization or death);5 6. Relevant therapeutic measures and laboratory data at baseline, during therapy, and subsequent to therapy, including blood levels, as appropriate; 7. Information about response to dechallenge and rechallenge; and 8. Any other relevant information (e.g., other details relating to the event or information on benefits received by the patient, if important to the assessment of the event).†6 Signal generation: A signal is reported information of the possible causal relationship between an adverse event and the drug, which has been reported more than once. The frequency of reports to generate a signal depends on the seriousness of the event, drug class, disease status, authenticity of the reporter etc. Signal follow-up and strengthening: Signal follow-up and strengthening consists of identifying similar cases in different countries, mining the literature for evidence to support the hypothesis, pre-clinical information and patient follow-up. The prospective analysis of reports of interests is crucial for a signal to generate any action. Careful scrutiny has to be done in order to assess the ingenuity of the signal. The report could have been due to the patients illness history, concomitant medication, disease state or any other reason not related to the use of drug. Even then, such confounded reports should be analyzed promptly. Signal follow-up ensures authenticity of the reports. Causality assessment: Determining whether the adverse event has a causal relationship with the drug or not, and if it has, the degree to which the association exists is called as causality assessment. The WHO has defined six degrees of relationship, namely: certain, probable, possible, unlikely, conditional/unclassified and unassessable/unclassifiable with lowering intensity of causality. Action: Action is taken once it is well established that there exists a causal relationship in between the drug and the adverse event. Depending on the severity of the adverse event, action taken can be in the form of withdrawal of marketing approval, change in package insert, additional trials to confirm causality and dissemination of information globally. THE PRACTICAL ASPECT: Consider the story of the blockbuster drug Avandia (rosiglitazone), used to treat patients with type II diabetes mellitus. â€Å"Rosiglitazone (Avandia ®) is a thiazolidinedione indicated in the treatment of type 2 diabetes mellitus: as monotherapy in patients (particularly overweight patients) inadequately controlled by diet and exercise for whom metformin is inappropriate because of contraindications or intolerance as dual oral therapy in combination with metformin, in patients (particularly overweight patients) with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin a sulphonylurea, only in patients who show intolerance to metformin or for whom metformin is contraindicated, with insufficient glycaemic control despite monotherapy with a sulphonylurea as triple oral therapy in combination with metformin and a sulphonylurea, in patients (particularly overweight patients) with insufficient glycaemic control despite dual oral therapy†4 Little did the world know that a boon was in fact a bane for a certain group of people with a history of cardiovascular illnesses. A meta-analysis by Nissen and Wolski et al. provided evidence that â€Å"rosiglitazone was associated with a significant increase in the risk of (MI)myocardial infarction (odds ratio, 1.43; 95% confidence interval [CI], 1.03 to 1.98; P = 0.03) and a borderline-significant finding for death from cardiovascular causes (odds ratio, 1.64; 95% CI, 0.98 to 2.74; P = 0.06).†2 Though the meta-analysis study had quite a few numbers of weaknesses, the increased risk of MI in patients consuming rosiglitazone has come as a rude shock to the sponsors as well as the patient community. Something, which could not be unveiled during the clinical trial process. Another study (called Antipsychotic drugs and heart muscle disorder in international pharmacovigilance: data mining study) by David Coulter et al. used a Bayesian confidence propagation network to analyze the correlation between anti-psychotic drugs and occurrences of cardiomyopathy and myocarditis. Though the study did not prove much, it did bring up an association between use of clozapine and incidences of heart disorders. It also scanned the WHO database and concluded that as compared to other anti-psychotic drugs, clozapine is more widely reported. A French pharmacovigilance study (called Reports of hypoglycemia associated with the use ACE inhibitors and other drugs: a case/non-case study in the French pharmacovigilance system database) by Nicholas Moore et al. set out to find any association between use of ACE inhibitors and incidences of hypoglycemia. The results attested that in fact there was no significant increase in the occurrences of hypoglycemia in patients on ACE inhibi tors. Such pharmacovigilance approaches add to the knowledge base of drugs and related Adverse Drug Reactions. Pharmacovigilance is a vital tool. There are various advances and approaches to good pharmacovigilance practices ranging from data mining studies to conducting global clinical trials. What approach is deemed best to yield the right results, only time will tell. CASE STUDY: THE CHRONICLE OF DIABETES MELLITUS TYPE II, AVANDIA, HOPE AND DEATH! Early in august 2006, Vivians mother had gone to the hospital for some routine cancer tests. However, what was supposed to be routine, did not turn out to be. The doctors found the left side of the patients body swollen. She was admitted immediately. On admission, the doctors found her heart swollen as well. Her heart was racing. Every trick in the trade was tried to get Vivians mother under control, but nothing seemed to work. Just a few days into her admission, she died, of cardiac arrest. Till the end, the doctors failed to find out the root cause for her death. However strange it may seem, the drug which she was taking for the past eight years, to control her blood sugar level has been the prime suspect and the causative agent of edema and myocardial infarction. The name, Avandia; generically known as Rosiglitazone. Vivians mother was put on Avandia since 1999, the drugs approval year. Her death occurred in august 2006. Precisely eight years of Avandia, took her life. Then in May 2007, came to light a stunning NEJM study which spilled the beans for GlaxoSmithKline. They found â€Å"a significant increase 43 percentin the risk for myocardial infarction -with rosiglitazone. They also found a 64 percent increased risk for death from other cardiovascular causes in people taking the drug. These findings were based on analyses of 42 clinical trials of the drug.†10 As a response to this, but probably too late for Vivian and her mother, FDA issued a public warning about the findings of the Avandia pharmacovigilance study. Patients with a bad cardiovascular history were now said to revise their use of Avandia. Either stop it, or lower the dose. The information directly applies to Vivians mother death. Vivian said â€Å"At the time I didnt realize that she had any cardiac problems. But there is a history of heart problems in my mothers family, including a history of heart murmurs. And my brother has a congenital heart defect, my mother was also on at least 13 drugs at the time she went to hospital.†10 A CRITICAL ANALYSIS Thats the tale of one drug and one death. But there have been many. And no noise is being made about it. What approach is the right approach for pharmacovigilance is still to be stereotyped. But so far, the structured ADR reporting systems and data mining seems to have turned the fortunes for Avandia. But for the time being lets spare Avandia, and concentrate our resources towards analyzing the situation of global pharmacovigilance. Does it really happen? What constitutes good pharmacovigilance practice? But one things for sure, the mindsets of sponsors and regulatory authorities needs to change. Things need to get crystallized. Vigilance should be policed. Conditional approval to market the drug should follow stringent laws. The two core issues surrounding pharmacovigilance are drug safety and the reputation of pharmaceuticals. Which one of those needs to be sacrificed does the time arise, is a million dollar question. The reputation, it should be. Compromising drug safety puts millions of patients at risk. Reputation can be back, but life, once gone, never returns, and so is Vivians mother. Even then, the reputation of GSK seems to be untouched. Vivians mother did have a history of cardiovascular illnesses, but still she was on the death drug for over eight years. Such an issue was never raised during any of the trials of Avandia. It is thanks to pharmacovigilance that the root cause analysis was performed and the association between Avandia and edema and myocardial infarction was established. If not completely, at least it has rung the bells at the FDA. It was no doubt too late for Vivians mother, but the information has the potential to save millions of life, now that the correlation has been ascertai ned. However, some issues in the meta-analysis also need to be addressed. The study combined data of 42 different clinical trials. Trials with different outcomes, disease states, patients, duration and many other differentiating factors have been combined to pool in the data. The data from varying trials can be sometimes conflicting. GSK argues, the most reliable way to assess the long-term safety of the trial is to conduct a long-term safety trial. Three long-term safety trials of Avandia have been conducted by GSK. Namely; ADOPT (A Diabetes Outcome Progression Trial), DREAM and RECORD. The studies back Avandias safety profile. No more than a minimalist increase in risk has been noted in one of the studies. Again, as Avandia is known to control the blood sugar level for a longer time, it said to have benefits outweighing the risks. The conflict will always remain. However, in such a scenario, the safety of patients should not in any way take a back seat. Sponsors and regulatory authorities along with consumers and healthcare professionals equal should take serious and committed steps to improve pharmacovigilance. The authenticity of the safety profile of Avandia will be demonstrated over time. But in any case, the death of Vivians mother cannot be reversed, not by me, nor by GSK nor by the FDA. CONCLUSION The coming years are bound to be very interesting on the pharmacovigilance front. The techniques regulatory agencies mandate to make PV more stringent will be worth waiting for. Sponsors will have to invest more money to establish the safety profile of the drug. Awareness among patients has to be created for better reporting of ADRs. The current approach to drug development focuses an intensive, strong and time-consuming pre approval process, but a similar standing is required post approval also. The transition from research to marketing has to be more governed with the research step not stopping at the marketing juncture. BIBLIOGRAPHY: Dhruv Kazi, Rosiglitazone and implications for pharmacovigilance, BMJ 2007;334:1233-1234 (16 June), doi:10.1136/bmj.39245.502546.BE Steven E. Nissen, M.D., and Kathy Wolski, M.P.H., Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes, n engl j med 356;24, vol. 356 no. 24 Bruce M. Psaty, M.D., Ph.D., and Curt D. Furberg, M.D., Ph.D., Rosiglitazone and Cardiovascular Risk, n engl j med 356;24 Overview of cardiac adverse drug reactions reported in association with rosiglitazone, Nederlands Bijwerkingen Centrum Lareb November 2007 V. Thawani1, S. Sharma2, K. Gharpure1, Pharmacovigilance: Is it possible if bannable medicines are available over the counter?, Indian J Pharmacol | June 2005 | Vol 37 | Issue 3 Guidance for Industry, Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), March 2005, Clinical Medical David M Coulter, Andrew Bate, Ronald H B Meyboom, Marie Lindquist, I Ralph Edwards, Antipsychotic drugs and heart muscle disorder in international pharmacovigilance: data mining study, BMJ VOLUME 322 19 MAY 2001, BMJ 2001;322:1207-9 Nicholas Moore et al., Reports of hypoglycemia associated with the use of ACE inhibitors and other drugs: a case/non-case study in French pharmacovigilance sysyem database, Br J Clin Pharmacol1997;44: 513-518, 1997 Blackwell Science Ltd. Data Assessment in Pharmacovigilance (powerpoint presentation), R.H.B. Meyboom Avandia: Meant to Help but Killed Instead March 30, 2008. By Lucy Campbell, Seed Newsvine

Saturday, January 18, 2020

Night of the Long Knives

The Night of the Long Knives(The Blood Purge) Hitler had an abundance of power due to the enabling act that was granted to him by President Hindenburg. Even with all his power, Hitler still felt threatened by the SA leaders. This lead to the Night of the long Knives June 29th, 1934. This purge was only the beginning of his conquest to be the dictatorial power of Germany. What happened on the Night of the Long Knives? And why did Hitler arrange it. What happened during the Night of the Long Knives? This event saw the wiping out of he SA leaders and other people that angered Hitler. Hitler ordered his SS troops to arrest the leaders of the SA and political figures. Hitler assembled a fairly large group of SS and regular police, and went to the Hanselbauer Hotel in Bad Wiessee. Ernest Rohm and his followers were staying there. Upon arriving at the hotel, Hitler personally arrested Rohm and high ranking officers of the SA. Hitler then headed back to Munich where he addressed an assembled crowd of party members and SA members, saying â€Å"the worst treachery in world istory. † Hitler told the crowd that â€Å"undisciplined and disobedient characters and asocial or diseased elements† would be annihilated. When he arrived back in Berlin, he radioed to Goring saying the codeword â€Å"kolibri† to let loose the execution squads on more unsuspecting people. Hitler also used this purge to make a move on the conservatives he found unreliable. Himmler, Goring and Hitler himself ordered the SS against old enemies. Kurt von Schliecher George Strasser (angered Hitler by resigning from the party) and Gustav Ritter von Kahr former Bavarian state commissioner who brought down the Beer Hall Putsch in 1923) The reasons why this purge happened was because Hitler feared that someone would try and over throw him, Rohm and the SA had the power to do so if they wanted (Rohm was the leader of the SA, the SA had a force of over 3 million men). So Hitler did what he t hought needed to happen. He got rid of the problems and anyone else he thought had the power to overthrow him. The Night of the Long Knives did not just remove those who opposed or threatened Hitlers position. It also got the army to sign an oath that Hitler needed. The army saw the SA as a threat to their authority because the SA outnumbered them, also Rohm spoke about taking over the regular army by including them with the ranks of the SA. This alarmed the army leaders. Hitler then made a pact with the army. If Rohm and the other SA leaders were removed then the army would be in control of the SA. However for that to occur the army had to sign an oath of loyalty to Hitler. Hitler told the public of this gruesome even on July 13th 1934. Hitler told the Reichstag. in this hour I was responsible for the fate of the German people, and I thereby I became the supreme judge of the German people. I gave order to shoot the ringleaders in this treason, and I further gave the order to cauterize down to the raw flesh the ulcers if this poisoning of the wells in our domestic life. Let the nation know that its existence- which depends on its internal order and security- cannot be threatened with impun ity by anyone! And let it be known for all the time to come that if anyone raises his hand to strike the state, then certain death is his lot† – Adolf Hitler, July 13th, 1934. he aftermath of the Night of the Long Knives aka â€Å"The Blood Purge. † Hitler got away with his purge because Hitler had the cabinet approve a measure on July 3rd that declared â€Å"The measures taken on June 30th to July 1st and 2 to suppress treasonous assaults are legal as acts of self-defense by the State. † A new law was added which was signed by Hitler, Franz Gurtner, and the Minister of the interior Wilhelm Frick. The new law legalized the murderes committed during the purge under treason. The army applauded the Night of the Long Knives nd President Hidenburg expressed his â€Å"profoundly felt gratitude† and he congratulated Hitler. Hitler rewarded Himmler by giving him control of the SS. Himmler would now only answer to Hitler. Also Hitler game himself President a s well as Chancellor, a new role called ‘Der Fuehrer'. He also made himself head of the armed forces, who swore an oath of loyalty. Adolf Hitler was now in complete control after President Hindenburgs death in August. The Night of the Long Knives occurred on June 29th 1934. Many high ranking officers of he SA were killed, including several of Hitlers partners executed in the purge. After the purge Hitler created another Nazi organization called the Schutzstaffel or also known as the SS. The SS became the most feared arm in Nazi Germany. The Night of the Long Knives was an action to get rid of those disagreeing with Hitler or getting in the way of his rise to power. He was scared that someone would attempt to overthrow him. The result was the rise of an even greater/ stronger paramilitary for the Nazis.

Thursday, January 9, 2020

Thoughts on Persuasive Essay Topics about Pilots in an Easy to Follow Manner

Thoughts on Persuasive Essay Topics about Pilots in an Easy to Follow Manner Evidently, you shouldn't purposely choose a topic that will bore your audience. It is going to be better in case you consider and understand your audience. The audience has to be convinced by means of an argument or application. Since your audiences listen to your speech, be sure your language is crystal clear and easy. The Do's and Don'ts of Persuasive Essay Topics about Pilots Another good idea is to receive some completely free essay examples of different kinds and on various subjects to find a general idea of the way in which a thriving debatable paper looks. A whole lot of students have a tendency to find writing a persuasive essay somewhat challenging because of the essence of the essay and its dynamics. There are just a few things that define whether an essay you're working on is going to be a good one. Remember that you may make funny argumentative essays if you do a few things. Vital Pieces of Persuasive Essay Topics about Pilots Keep in mind, persuasive essay topics don't need to be politically correct all the moment, they may be controversial. If you're thinking about how to compose a persuasive essay, you have to know that writing an essay is a complicated practice. Persuasive essays share a good deal of resemblance with argumentative essays. All persuasive essays are like argumentative essays. When you're writing such essay, the purpose is to come out with the ideal college essays. Aside from the mentioned above classification essay topics, there are lots of others which we may supply you with. The Foolproof Persuasive Essay Topics about Pilots Strategy Normally, having three significant arguments to show your point is sufficient for a convincing paper. Remember your essay shouldn't be a string of jokes, it's a narrative it ought to have a start, middle and the end. Zodiac signs changed with the debut of the 13th. Once you choose the subject, you must center on the principal points of the speech. Identity theft is a very big issue for elderly folks. Immigrants shouldn't be treated as criminals. Racial profiling ought to be done. Students need to be careful about posting on social networking. Our qualified academic experts will help you to find an ideal persuasive essay topic according to all of your requirements and compose a custom-tailored model answer. To help students just like you find debatable topics, we've gathered a vast range of ideas on unique subjects and academic levels. Students often stress about trying to find utile persuasive essay tips and searching for ideas due to the fact that they feel it's an uphill job, but the crucial thing is to understand the essence and make a suitable outline first by planning for it correctly. From time to time, employing the very same topics over and over again makes they bored and unable to find inspiration to write essays. Textbooks are obsolete and ought to be replaced by iPads. Teachers should also need to go through professional tests like students. Students ought to be permitted to pray in school. They are used to the fact that their professors give them the assignment's topic. To choose which subject you're likely to discuss, it's essential to see the complete collection of good persuasive speech topics from the special area of study. You may trust us to supply expert aid f or many of your academic writing needs. It's important to understand that essay topics are just basic ideas that leave you pondering a notion that might be a huge deal to somebody else. Deciding on the correct topic for a persuasive speech may be not such an easy issue to do as it might appear. The Ultimate Persuasive Essay Topics about Pilots Trick At precisely the same time, it's a terrific persuasive essay idea. The simplest approach to pick a persuasive essay topic is to go over a present issue. All things considered, you can observe that writing a persuasive essay isn't a brain surgery. Certain persuasive essay prompts can earn a topic a lot easier to write about or there may be a difference if there's a strong opinion to generate a subject easier to be persuasive about. Schools should not have anything to do with ads. For instance, you want to classify your textbooks. Honestly, you simply have to place an order with your requirements and your speech is going to be do ne as quickly as possible. Because you have read hilarious persuasive speech topics and can pick the one that you need to write about, you can write a great speech.

Wednesday, January 1, 2020

The Privacy Of The Media - 988 Words

Privacy are one of those things that we re humans believe we are entitled to either through nature or law but even with our beliefs, privacy is one of those topics that are going to be discussed in a large extent in years to come because as humans, we are still struggling to find the balance between privacy and intrusion. When looking into privacy in the media today, one of the most discussed topics is about the government violating the citizen’s privacy while the government maintains that it all about safety procedure and maintaining national security. Edward Snowden the whistle blower from the CIA whom brought our attention to the government privacy intrusion in its citizens lives reminds me of the privacy/ openness problem that families are having in general. Edward Snowden reminded me of the problems that families are having with being able to be open with each other in the sense that Edward felt like tit was the citizens right to know about what the government was doing t o or towards them while some people especially the government Claims that it was not Edwards secret to tell and it was all about the good of the nation and when looking at the conflict between the citizens whom supported Edward to the ones whom felt like he had no right to leak those secrets, the conflict between the citizens whom believe that he did the right thing to those whom felt like he didn’t is the same conflict that we see in families especially in the topic of openness vs. privacy.Show MoreRelatedMedia Invasion of Privacy5852 Words   |  24 Pages A TERM PAPER SUBMITTED IN PARTIAL FULFILLMENT OF THE COURSE: ETHICS AND PROFESSIONAL PRACTISE (MAC 854) LECTURER: DR. 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Studies have found that invasion in privacy is a result of multiple factors like lack of consumer knowledge, low self-esteem, growing comfort, trust, generation of revenue and a lack of standards which lead to occurrence of harmfulRead MoreComprehensive Legislation Of Social Media Privacy1559 Words   |  7 Pages Comprehensive Legislation to Protect Social Media Privacy Reading and Writing Workshop II, Section 007 Qiu Jin (Rachel) August 11, 2014 Comprehensive Legislation to Protect Social Media Privacy Abstract The article makes a research on both the present situation of social media users’ privacy, and the work of the FTC and other federal departments to protect social media privacy. However, without a comprehensive legislation in the federal level, the fragmentation of such trial cannotRead MorePrivacy Issues in Social Media Essay1278 Words   |  6 Pages Privacy Issues in Social Media Social Media is a current way in which people are using to interact with one another daily. 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It is something about social media that make us loose our sense of reason and place all sorts of personal information on the Internet for all the world to see. But, social media is not the only reason for the privacy breech. There are many reasons, and computer hackers are just one. Our emailRead MoreSocial Media And Its Effect On Individual Privacy944 Words   |  4 Pages However, in a complex network where millions of people can create and post their daily lives, the collection and analysis of personal information by online social networking sites has been controversial due to its potential to weaken individual privacy. The online platforms are owned by businesses that have the goal to optimize performance for users but also can turn the masses of users into monetary value by data mining. Global multime dia networks and the advertising industry have become interestedRead More Privacy Rights and Social Media Essay1538 Words   |  7 PagesA person’s right to privacy is being challenged with the high use of social media such as Facebook and Twitter. What used to be considered part of your personal life is not so personal anymore. When one chooses to share details about ones-self to their friends via a social media, they are not always thinking about the â€Å"other† people. The other people could be ones current boss or future employer. Other people could be a school official, your baseball coach, your friends’ mother; you name it the listRead MoreSocial Media Is A Big Invasion Of Privacy915 Words   |  4 Pages Social media has taken over the modern day world. It has helped us to communicate, share information, keep in touch, etc. We often forget about the problems it causes. Social media causes ethical dilemmas such as violations of misrepresentation, privacy, cyber bullying, and spying. Social media sites such as Facebook, Twitter, Instagram, and Snapchat have made the world what it is today. Although, social media helps us tremendously, we have to be very careful that we do not abuse it. In the