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Lime Crime’s Various ControversiesLime Crime’s 10th Birthday Eyeshadow Palette (image: Look Fantastic)What is Lime Crime?Lime Crime is an American independent beauty company launched by Doe Deere (a.k.a. Xenia Vortova) in 2008. Before officially launching her business, Deere sold her cosmetics exclusively on eBay. Lime Crime gained a cult following before becoming a mainstream name. The company was originally known for its Lolita-style makeup and its vibrant colors.Lime Crime soon became the center of scandal and controversy and today, many people still won’t buy from them. Their shady business practices have marred their name and reputation for good.I will break down each of the controversies below so you can decide for yourself if you want to buy from them. These are just the facts I found online, so decide at your own risk.Controversy #1: Doe Deere Dressed As HitlerIn 2007, shortly before her public launch, Doe Deere dressed as Adolf Hitler for Halloween. As questionable as it is for anyone to dress for Hitler, it’s somehow slightly worse when you’re a public figure or aspiring to be one.(image: Doe Deere Blogzine)Even by 2007 standards, the costume was not in good taste. Deere never offered an apology for her costume choice or to try to cover her actions.Controversy #2: The 2009 Repackaging ScandalOne of the biggest followings on the internet is the beauty blogger community. What the bloggers have to say about a makeup company can make or break it. Beauty influencers are the pinnacle of the beauty industry and Doe Deere knew this.In 2009, just a year after Lime Crime launched as its own business, beauty bloggers began to question if Deere and Lime Crime repackaged wholesale products. The first similarity was noticed by a blogger named Anastasia who ran a blog called Lipsticks and Lightsabers who found that the pigments looked like those from TKB Trading, a wholesale company selling the eyeshadows at a third of Lime Crime’s price.Lime Crime pigments vs. TKB Trading wholesale pigments from the now Lipstick and Lightsabers blog (image: Lipstick and Lightsabers via Revelist)Doe Deere was not happy about this and she sued U.S. bloggers writing anything critical about the dupes or Lime Crime. Deere claimed that one critic’s blog called Doe Deere Lies cost Lime Crime approximately $250,000 in sales.In addition, Deere sent a cease and desist letter to a beauty blogger known as Grey, who ran Le Gothique. Deere threatened legal action against Grey if she did not delete her review and replace it with an apology, which Lime Crime provided.Controversy #3: The 2012 “China Doll” Palette(image: The Doe Deere Blogazine)In 2012, Doe Deere and Lime Crime announced the Chinadoll Palette, which immediately struck controversy. The palette’s advertisements did not feature a woman of Chinese descent which bothered many people. One Vietnamese Beauty Blogger named Mai says it better than I can:“ …the campaign was done in a culturally insensitive way and the entire thing is rather ignorant of Chinese culture, past and present.”Doe Deere took to her Blogazine to address the issue, defending her palette. She said the following about cultural appropriation and the claims bloggers were giving: "To summarize, it’s the borrowing of certain cultural elements by another cultural group. To be honest, I find the notion a little silly. Not all that pertains to race has to be racist, just like not every cultural reference has to be met with opposition. What matters is intent. As an artist and a human being, I have the right to be inspired by and wanting to explore, adapt, and otherwise express myself through things I find wonderful."Controversy #4: The Data Breach of 2014In 2014, Lime Crime’s website was hacked. The hack caused a massive data breach, and the hackers took $100,000 in money from Lime Crime customers who saved their credit card information.Instead of being upfront with their customers and sending them an e-mail, Lime Crime took the matter to Instagram. The apology and resolution provided in the post seemed especially inappropriate, because scattered in the apology were emojis.The hack occurred because the company may have been using an expired SSL certificate (the security system used by most major websites to protect customers’ data). Some Instagram and Reddit users affected by the breach said that Lime Crime never refunded them.Controversy #5: The Great 2015 FDA ScandalThe U.S. Food and Drug Administration (FDA) came down on Lime Crime in 2015, after their red velvet shade of the brand’s popular Velvetines Liquid Matte Lipsticks contained ferrocyanide and ultramarines. These chemicals are not accepted for use by the FDA.(image: Lime Crime)The FDA investigation came after at least six complaints from customers. They claim Lime Crime ignored their requests for more information and were simply blocked on social media.Lime Crime said that this was a packaging error, removing the ingredients off of the packaging.Controversy #6: Vegan or Not?Lime Crime prides itself on being a vegan make-up company and being cruelty-free. But some bloggers believe this is not true.Some screenshots from beauty blogs show that their lipsticks contain petroleum, which is not a vegan ingredient. Some also contain beeswax and carmine.More so, it is speculated that Lime Crime tests on animals and is lying about their cruelty-free status.Lime Crime apologized and claimed they removed the ingredients from the lipstick but some say they just removed the ingredients from the packaging.Controversy #7: Rusted Eyeshadow PansIn 2016, Lime Crime released a sparkly eyeshadow called Superfoil. The eyeshadow became the talk of the internet, but not for a good reason.Bloggers and Lime Crime fans found that the pans used for the eyeshadow were moldy and rusty.(image: Britt WD)Lime Crime claims that the glycerin in the eyeshadow causes the pans to “discolor”. People became wary of the product.Sources:Grey’s Post on Le GothiqueHow "cruelty free" are lime Crime really?Lime Crime & The Scary Truth About Product SafetyLime Crime: The Issue of Cultural AppropriationLime Crime's Website Is Hacked, Customer Information StolenPeople Are Freaking Over Lime Crime's SuperfoilsThe Match of the Century:Retail-vs-Wholesale PigmentsWhy Lime Crime Is the Most Hated Beauty Company on the Internet

As a person who has made drugs and is planning on making a career out of it, I hope that a lot of things change by the time I reach the middle of my career. The ideal drug development process would and should look very different from the current system in place.The interesting thing is that most of the interactions that already exists should stay in place. A large problem with the current inefficiency of the drug discovery / development process is that the incentives and goals are misaligned for all of the individual players in the drug making process. It's certainly an acknowledged problem and everyone in the drug industry talks about it. To describe how deep of a hole we're in, I show you Eroom's law (Moore backwards) which suggests that the cost of developing a new drug doubles every nine years.EROOM's Law [1]This is pretty unsustainable and Pharma knows it so there are a lot of experiments and proposals to change the drug development process so that failures occur earlier and successes are identified early and pushed through.Everything I will describe tackles the underlying goal of reducing the attrition rate and costs of the drug development pipeline. To briefly outline MY OWN opinions on what needs to happen to have a cost effective system I'm going to dive into:Adjusting the goals of academic research to focus on clinically relevant areas.Changing how medical research appropriately informs and guides that basic researchBridging the gaps between academic and industrial research by both academic efforts and increased drug companies' fundingDiversifying risk between the various stages of drug development by focusing on individual strengths.Revamping the clinical trial process, drug approval system, and influence of marketing to allow for smaller but faster trials.Integrating the drug distribution system into the healthcare networkCreating and rewiring the feedback loops between all of these systemsThe Role of Basic ScienceLet's start from the beginning. Academics are certainly the seed and start of medical discovery and innovation. They ask the questions we don't know the answers to and also find them and from their understanding of biology, chemistry, and medicine, the drug companies can take things to the next level.Unfortunately, the targets that are hot topics in academic will very often be undruggable targets or at least very hard to hit. Targets like protein-protein interactions, transcription factors, protein aggregates, ubiquitin modifiers, RNA, and epigenetic regulators.[2] A great example of a protein target that receives a lot of attention but is completely undruggable is p53 as described in Can p53 be synthesized into a drug to target cancer? It's a target that is extremely dynamic, has a multitude of interactions, and has plenty of off-target effects. People may get the impression that maybe one day we'll figure a way how to make it a useful drug but in reality, we'll probably never hit it and it's merely an very interesting topic of study in molecular biology (with great scientific importance I would add).The result is ~2% of the human genes are actually druggable which largely separates what academics work on and say we can cure vs. what drug companies can actually cure. [3] I describe this more in my answer to Human Genome Project: Was all the promise publicized by the media during the mapping of the human genome simply hype? and Why has genomics been so unsuccessful in the discovery of new medicines?Every now and then, one of those "undruggable" targets become druggable with the invention of new technologies or chemistries. Things like recombinant technology, antibodies, stapled peptides, and PEGylation have made it possible to attack new targets. Indeed one of the widely assumed "undruggable" targets, K-RAS, was recently targeted by a team from Max Planck using a combination of structure-based drug design.[4] Yet there is still is separation from what academics are working on and what companies can actually do.This was well stated by Stuart Schreiber (who, I note, gave me much of the structure of this portion of the argument): Academic research ... might have a greater impact if it were redirected to developing methods that change our view of what is doable. [5] While there is much talk about target-based drug discovery, the modern era hasn't produced much in terms of drugs and a large part is the failure for basic science researchers to choose good targets. [6]The fixture to this issue would be toHave real MSTPs. A good number of MD/PhDs don't end up going into research or they lose too much momentum because of residency. Having true hybrid scientists will help bridge that gap between what patients need and what is actually possible.Clearer discussions on what is and isn't "druggable". As others have mentioned, scientists should be doing a better job looking at the final product rather than thinking about what applications their recent discovery can be applied to.Improvement on target identification. People need to recognize signal from noise and unfortunately there is a lot of noise.Commitments to developing new chemistries and technologies to target the "undruggable" space.Better academia/pharma interactions.The first two are cultural things that academics need to be less stubborn about. The third is an area ripe for progress. As mentioned by Taffy Williams and Mike Thompson, the advent of personalized medicine drastically improves the ability to relate a disease to it's molecular mechanism of action. Furthermore, HTS technologies are designed to be more amenable to diseased-based drug discovery rather than target or gene-based. To better connect academic research with disease, we need to go further into the chain to medical research.Connecting Physicians and ScientistsDrug discovery really starts with observations in the clinic. Doctors will observe patients and from recognizing patterns, they will have a better idea of what makes up a disease and maybe begin to have an idea of the underlying mechanism. I go into this more in my answer to How do pharmaceutical companies go about finding cures for diseases?The problem with this model is that doctors are notoriously bad at doing science and statistics and either see patterns out of nothing or will run trivial investigator initiated trials that are under-powered, biased, non-randomized, non-placebo controlled, and poorly designed. Again, a large reason why better Medical Scientists are required in medicine.The ideal situation is better data collection using Electronic Medical Records and releasing that data from the EMR companies so that information about patient habits, diagnoses of disease can be used. Unfortunately, this information is very difficult to get unless we have a complete overhaul of the healthcare system which I will go into later. I illustrate the value of having this data with the alternative route.For now, I suggest reading the 5 part series: How to build a good EMR by Jae Won JohThe existing model for data collection is the use of patient communities like Susan Komen and Cystic Fibrosis Foundation, which have been extremely helpful to both doctors and pharmaceutical companies. It helps to link symptoms to the underlying case of disease and pools together the patient populations to understand the epidemiology and guide companies to which drugs will have the broadest effect.As seen in questions below, there are very good reasons for pharmaceutical companies to create a strong patient community to better understand the disease and to help with clinical trial enrollment.How should Pharma work with online patient communities?Which pharma companies are currently working with online patient communities?Should pharmaceutical companies support existing online patient communities or create their own?This has been extremely effective in the Rare disease community in collecting and sharing data to better inform patients, doctors, and drug companies. However, a shared worldwide network that better captures all of the variance of the disease will vastly improve physicians' ability to systematically track trends along with maintain a consistent standard of care. Furthermore, in post-approval studies, this type of network allows us to better identify side effects and drug-tolerant patient populations.The Bridge to PharmaceuticaObviously this isn't merely academia's fault. Pharmaceutical companies need to carry their weight in the drug discovery side. Given the large amount of money that is already dumped into research it is important to prioritize research funding. However, the use of those funds are currently poorly utilized.I go more into the economics in the marketing section but for now, it is important to realize that there are large non-trivial cost barriers from translating an idea from academia to company. As every startup knows, there is something called the "valley of DEATH".[7]Ignoring the y-axis "cumulative profit/loss" and replacing it with "expected value", the graph is essentially the same in the eyes of Venture Capital and investors. During the early stages of drug development, the probability of success is extremely low and expected value of the drug is equally low. Only after a lot of time and money does the "commercialization" or the proof of concept occurs and a drug becomes worth investing in.Unfortunately for the biotech industry, the valley of death usually coincides with a Phase II clinical trial which takes ~$20-100 million dollars to get to which can be demonstrated with the next figure [8].So either VCs need to start doing a series A earlier during the process and regularly fund companies pre-IND, pre-Phase III or another large player needs to step in. In addition, academic groups need to do a better job connecting their publications to the final product to reduce uncertainty and risk.This is probably the most exciting current area of drug development as it requires the least amount of momentum to achieve large meaningful results. Universities, Drug companies, and VCs are largely experimenting with how they are tacking this cap.Academics making their drug fundableI'll start with what Academics. I mentioned earlier that Academics tend to work on problems that don't usually yield to tangible results. However a deeper issue is not realizing the disconnect between a successful publication and the commercialization of that idea.The inability to draw in a licensing deal or VC funding can be summarized by:A poor understanding of the economics of the diseaseLack of meaningful clinically relevant dataAn inability in academia to weed out false positives.A poor understanding of the economics of the diseaseSince most PhDs aren't MBAs, they really have no clue how health insurance works and how much drugs actually cost. Typically the way how research is funded is:Find something coolFind what that cool thing doesSee if that thing it do is usefulJustify doing more research on that cool thing based on what it doesTotally reasonable way of doing research but it's also the reason why the NSF is getting in trouble with Lamar Smith. Essentially most of biological research is driven by finding random applications of the science rather than finding the appropriate application and making involved hypotheses to guide that science.For academics to seriously make an impact, they must first check in with the physicians to see what actually happens in the disease that they are interested in and then adjusting the drug in a manner than is suitable for that disease.For instance, several "cures" of HIV including bone marrow transplants and aggressive antibody treatments are impractical since a handful of "inexpensive" oral drugs will essentially do the same + be safer.Lack of meaningful Clinically relevant dataEveryone has seen the article "X cures cancer". What most people forget to do is to read the small text "this might be useful as a drug in 15-20 years". Typically these high-impact publications go along the lines of demonstrating efficacy in an early model system and then following up those observations with the next logical series of experiments.The common saying in the drug discovery world is that "you get what you screen for". As critics of the pharmaceutical industry will say, we're good at curing mice. While we still face the same drug development issues when we attempt to treat mice, the result remains the same, our drug discovery pipeline isn't optimized for finding drugs that treat human diseases. That is, things like chemical-based screening and target-based screening doesn't necessarily produce clinically relevant results. As mentioned, later, the major sources of failure come from lack of efficacy or toxicity. This basically suggests that you've chosen the wrong target to attack.The alternative is to design the screens to identify clinically relevant compounds from the start. Using disease-specific cell-based assays are one method. Using several filters for activity is another. There are also several efforts to build better mice models which actually have human immune systems and die from human cancers. The world of iPSCs also opens the door to the creation of immortalized cells that come directed from a diseased patient.The ideal scenario is to change drug discovery from a linear process to an integrated research pipeline which eliminates false positives from the start. I'll go more into the research integration later.Proposal for bridging the valley of death [9]An inability in academia to weed out false positives.Certainly a sensitive topic in research is the question Is most medical research wrong? Why or why not?A classic paper Why Most Published Research Findings Are False by John Ioannidis suggests that there is an unfortunate tendency for publications to select for positive data. In my own answer, I claim that this falsehood comes from the misinterpretation of the data and answer by Manish Kothari and Michael W. Long also go along those lines. It surprisingly isn't because of fraud or data manipulation, it's more that people are pressured into seeing what they want to see and making the wrong analysis.This issue also reflects the very difficult task of reproducing research. As a personal example, we have one company that is trying to replicate our data using a similar experimental setup and they were failing to do so. In fact, they had to send "experts" to directly observe my labmate doing his experiment and even made him use their own reagents to confirm. Ultimately we narrowed it down to them using a poor source of a few reagents along with forgetting to mix certain chemicals in a certain order. Unfortunately the guy who figured this all out left so after we taught this information, we had to teach it all over again.A lesser known study done by Bayer and Amgen formed validation teams that essentially spend a year trying to reproduce other people's data. Their conclusion: ~20-25% of the data was reproducible; 2/3 of the data there were inconsistencies. [10]Again, this isn't because of fraud or data manipulation. In many of these cases, the teams had to replace cell lines or change the assay formats to get the hypothesis to work. However, even then, there were inconsistencies. There is a lot of variation in biology and are several factors that may cause a false positive.The moral is: Just because your paper was accepted in Nature, it still doesn't mean that it's scientifically sound enough to spend $1 billion dollars on it. To successfully and scientifically validate your idea to the point where a company is willing to take a risk requires several confirmations of your idea. If the drug works in an assay, use a new assay; if it works in another assay, use a cell-based assay; if it works in a cell-based assay, use another cell-based assay; if it works in that cell-based assay, use a mouse; if it works in a mouse, use a rat; etc. See How do drug researchers address effects that only occur in rats?For intellectual pursuits, these studies may not be particularly rewarding but they are the scientifically correct thing to do and ultimately brings in investors. There is also the whole revamping of the publishing model which I will also go into later.I conclude this chapter with a brief telling of The Sirtuin Saga regarding Resveratrol.[11]Triggered by a study by David Sinclair in 2003 that suggested that the molecule in red wine extended the lifespan of yeast cells and at one point showed the reduction of aging in mice. The resulted in the starting of the biotech company Sirtis which ultimately got acquired by GSK for $720 million. However, later studies suggested that the in vitro assays that suggested this activity had some artifacts due to the presence of the fluorescent molecule used in the experiment. Recent data suggests that the assay only worked in specific conditions but still worked. In the end, the scientists did isolated activity, they just started a ~$1 billion company off the wrong lead compound. [12] [13]This debate itself has lead to multiple Quora questionsDo sirtuins really lengthen lifespan?Does resveratrol keep our cells from aging?Why is red wine good for you?If you ask Alex K. Chen for his opinion, the answer is maybe.Academic pipelinesIn order to get researchers to recognize these pitfalls, Universities have created internal pipelines to help academically minded people solidify business-friendly science that can be outsourced.Most of these groups help Professors and students get through the hurdles mentioned above and uses industrial expertise to indicate what risks remain with the proposed technology. Ultimately these ideas would become mature enough to be licensed or spun out into a company and allow Professors to get back to their professing.A few of these programs already exist and the best examples includeStanford SPARKMIT NEWDIGSNorthwetern CMIDDEmory Institute for Drug DevelopmentU Toronto MaRSUCSF CDDSDrug companies funding academicsAs the academics reduce their risk, companies and VCs need to do a better job taking risks. There are usually two schools of though on how to approach this problem.Drug companies should start pulling out the checkbooks and with an aggressive M&A or partnerships fund early stage researchDiversify the risk to Contract Research Organizations and let them handle early stage Clinical development.Those who believe in virtual and lean startups will tell you to go with option 2 and since they have a MBA, they are probably right. I will tell you to go with option 1 since only Pharmaceutical companies had the long term discipline and vision to prevent further fragmentation of an already shaky potential drug. The current reality is something in the middle since Pharma companies are too unweldy to move quickly through development and small biotechs are too desperate to do good science.The ideal model is a Pharma funded early stage pipeline program that operates independently of the mother program but has the financial and intellectual capital to success.Good examples of these early pipeline programs includeGenentech (gRED) / RocheChorus / LillyCORTEX / PfizerCentocor/ JnJBad examples of early pipeline programs that weren't independent includeGroton / PfizerSandwich / PfizerKalamazoo / PfizerWyeth / PfizerKent / PfizerSirtris / GSKResearch Triangle / GSKHarlow / GSKWhitehouse Station / MerckBasically don't be Pfizer. What essentially happened was that pharmaceutical management interfered with early R&D and started outsourcing certain functions to other countries with "expertise" for the sake of "efficiency". However, what that actually means is waiting for a chemist in China to ship their compound to the assay development team in North Carolina which uses a protein created in Switzerland. It's pretty much guaranteed to not work. What you really want is a small well funded mini biotech that cranks out a bunch of compounds.GSK had shifted to a Therapy Area Units (TAUs) system but they are in trouble since they keep on changing the model every 8 years whenever they get a new CEO. Novartis uses the NBIR model; JnJ never bothered to integrate their units; Roches has pRED and gRED; Merck stuck with MRL but the new R&D chief is proposing an aggressive reshuffling at the time of writing. [14]Pfizer has changed their research model from independent research labs to "Centers of Therapeutic Innovation" which collaborate heavily with several Universities. They are essentially outsourcing all of their R&D to academic labs. Probably a wise move but probably not worth imploding their research units.In summary: Pharmaceutical Managers needs to stop moving units around every ten years especially involving products that take 15 years to work.Part of this is a disciplined approach to outsourcing which gets back to the MBA's approach to doing research. There is a lot of value in contracting out research.It allows companies to focus on what they are good at.Reduces training time of new hiresSpreads out capital costs (especially with contract manufacturing)Where this quickly goes wrong is when expertise gets lost and communications gets severed. I mentioned my own outsourcing story earlier and Derek Lowe has several deep and bitter discussions on the problems of outsourcing. When outsourcing causes you to spend more time troubleshooting your supply chain rather than doing science, you're sacrificing time and money. [15]Making Marketing Departments SHUT UPAccording to Adithya Balasubramanian's answer to What is the detailed cost breakdown of an expensive clinical trial? ~90% of the cost to approve a single drug comes during the Phase III clinical trial. Phase III trials are expensive and unfortunately still fail 40% of the time.The major reasons behind failure: efficacy and toxicity. [16]At some point we had information from Phase II trials that informed us that this drug had a pretty good shot at working. As indicated in the cost breakdown, In addition to the fact that they already cost a lot, Phase III trials are get more expensive because they are getting longer, more complicated, have a lower patient retention rate, lower patient enrollment rate. All in all, we are being too aggressive with the way how we design clinical trials and pushing compounds into phase III.A good example of getting impatient and going blindly into Phase 3 trial was the recent Pfizer, JnJ, and Elan efforts with Alzheimer's and blew over $1 billion on two trials with Bapineuzumab despite very indifferent Phase II data. See Where did most of the money in the failed Bapineuzmab Alzheimer’s antibody phase III trial go? The companies had their eye on the $5 billion / year Alzheimer's market but didn't allow the science to dictate their strategy and placed a bad gamble. [17]My hypothesis is that we rush to Phase III too quickly and design the trials to be too broad. If the Phase II data indicates that the drug works in half of the patients, we should be testing the drug in the responsive half. The marketing team will say, that's too complicated, let's test all of the patients and get twice as much money obtaining a blockbuster.The unfortunate result is to appropriately design a suitable trial, you will need a larger subject population and a longer enrollment period to sufficiently power the trial. This ultimately will cost several times more and has a higher chance of failure than designing a smaller well powered trial. This comes back to efficacy and toxicity. If you have a good idea which patients will likely show the best efficacy and least toxicity, you should design your trial for those patients. As mentioned earlier, this is partially due to choosing an incorrect target. However, enrolling the patients that have the wrong target is also a sure way to get a dud.The clinical trial that goes against this tide was Herceptin which looked to attack a gene that was expressed in only 20% of Breast Cancers. From a disciplined scientific approach, Genentech resisted the pressure of increasing their market size 5x by narrowing into the smaller group of Her2-positive patients. Doing so allowed them to use a significantly smaller population (10-20 times smaller) and get approval more quickly.However, there is a reasonable question whether the marketing people were right. Recent reports do suggest that Herceptin works even for certain Her2 negative patients and a non-trivial proportion of Doctors don't pay attention to Her2 status prior to prescribing the drug. In the end, you want the broadest indication since it gets you the most money in the brief period of time the drug patent exists. Marketing got their Blockbuster anyways.You can't blame Pharma companies for thinking this way. I;m sure that some MBA has shown that taking these type of these aggressive gambles should actually get more money in the short term despite the higher failure rate. As a result, to incentivize a trend towards these smaller but better designed trials we need to have an overhaul of the drug approval process.A new interaction between the FDA, Insurance, and PharmacyWhile a lot of drugs fail simply because we didn't identify failiures early like in the case of Bapi, there are some drugs that failed since too many non-responders were enrolled. In my non-medical opinion, drugs like Vioxx and Avandia should probably be on the market since they do work despite what Steve Nissen says. Their problem is that they are being marketed to the wrong people.Despite the large controversy in data reporting for Rofecoxib (Vioxx), it was an extremely effective drug for some patients. It certainly had risks but both the US and Canada voted in favor of allowing the drug to be returned since they thought that the benefits outweighed the risks. However, the publicity hit already happened and Merck decided to permanently withdraw the drug.Another good drug that had devastating side effects was Thalidomide, the drug that triggered the strengthening of the FDA in the first place. The drug infamously caused numerous birth-defects and was quickly withdrawn from the market. As we can see in Can Thalidomide -- a drug with an exceptionally controversial history -- actually be used to treat multiple diseases as claimed in the article cited below? the once dangerous drug has reemerged as a potential Multiple Myeloma drug.This brings us into need to change the drug approval process. The potential of Pharmacogenomics can significantly change our ability to rationally identify patients who will respond well to drugs. This allows us to better design clinical trials that will enroll patients.The risk of these trials are still high and there are real concerns about generating enough of a profit to bridge the valley of death.The appropriate proposal is the use of adaptive licensing, which takes advantage of accelerated approvals to start charging patients to recuperate the costs of drug development but under extremely restrictive conditions. However, while it may cost more per patient initially, it does lower the barrier to entry and reduces the time spent in the valley of death.Depiction of Adaptive licensing [18]A good example is the recent approval of Lomitapide which ran a tiny 29 patient phase III trial for the ultra-rare genetic disease homozygous familial hypercholesterolaemia and got FDA and EMA approval for only that indication. However, the compound has potential efficacy in hetereozygous patients and with the initial approval in the small patient population, they should have enough cashflow to initiate the larger phase III trials.This is heavily on the FDA to allow these trial designs to occur. Their role is to ensure that efficacy and safety are in place. With that in mind, they need to reassure companies that they won't consider these early stage Phase III trials as "proof of concept" trials and are willing to look at earlier NDA fillings.It should be acknowledged that reducing the patient population does complicate enrollment and as indicated by several answerers in What are some of the biggest challenges with setting up and conducting clinical trials? enrollment is one of the hardest steps with clinical trials. However, by tapping in to the patient communities and the use of smaller trial designs, I am hopeful that this dilemma can be resolved.Closing the Feedback LoopTypically when you see something about drug development you see funnel like this:I've always hated this diagram.It makes the entire drug development process seems extremely linear and essentially the secret to getting a drug is taking more shots. Also it assumes that failure is built into the process.The real drug development diagram looks more like the next two diagrams [19]The key thing that makes these proposed systems work is the ability to use the current data to better design future experiments. Rather than working on several compounds and removing them by a process of elimination, you're working on a single product that gradually gets refined and polished by the time it reaches approval. Failures should lead to new hypotheses and guide the development rather than close the door. For this loop to be complete several things need to change.Doctors and InsuranceThese folks were blamed before but now they are getting blamed again. For adaptive approvals to work, Doctors will have to restrain one of their most powerful tools: off-label use. At the same time, insurance companies need to do a better job enabling off-label use when it is appropriate.As mentioned, Doctors need to do a better job observing and reporting patient outcomes. With the increased role of Phase IV monitoring this becomes even more important. Doctors will also need to adjust to the increased role of companion diagnostics and personalized genomics information. For instance, an abnormally large percentage of doctors prescribe herceptin without checking their patient's HER2 status. While the next wave of doctors are beginning to be trained with this mindset, a full overhaul of medical practice won't occur for at least another 30 years when veterans finally die out (however, we still want our Drs on Quora to live forever). However, even the current medical education that was given to people like Jae Won Joh and James Pan doesn't fully integrate a mindset of using personalized medicine.Insurance companies will also need to shift from a high-deductible mindset to a preventative mindset. Drugs in the US are still extremely expensive to the end-user and insurance companies aren't doing enough to negotiate those prices down and appropriately. They will also need to shift from a disease-based model to a target-based model. We can no longer treat breast cancer as breast cancer but instead, treat HER2-positives vs. EGFR-positive cancers. With these systems in place, drug repurposing would become more easy to recognize and push through.Completing this side of the feedback loop will be a key step. For this to happen, Electronic Medical Records will have to be commonplace and better and systematic data collection needs to be implemented.The interesting arena of clinical trials with personalized medicine are the MD Anderson BATTLE Trial and the British Columbia Cancer Agency's Utilization of Genomic Information to Augment Chemotherapy Decision-making for People With Incurable Malignancies in combination with PREDICT. These efforts use full genome sequencing from single-patients in attempts to do personalized cancer treatments. However, according to Marco Marra (I saw him at a conference), there are all sorts of logistical hurdles including biopsy collection and access to off-label drugs. There is also the whole inability to making meaningful connections between genomic datasets and the root cause of cancer.Revamping Data TransparencyAs it can be seen in questions likeMedical Research: Are a significant fraction of drug studies private and not released out to the public?Food & Drug Administration: What is the best way to track the progress of experimental treatments undergoing clinical trials?Where can I find meta-analysis reports on clinical trials?Is every clinical trial recorded on ClinicalTrials.gov?Is that true the clinical trials or biology research data in university labs are chaos and not recorded properly for a feasible usage of the co-worker and the succeeded researcher?Is most medical research wrong? Why or why not?There are all sorts of problems with collecting and releasing data. Again, it's not as if we're doing all sorts of fraud and making stuff up (at least most of us). I've already talked about this extensively in the section: An inability in academia to weed out false positives. In addition to the steps to validate those results, another major change would be to incentivize the publication of more negative data.To ask private companies to publish negative results, we must first ask this of our own government sponsored researchers. The bias towards positive data and the lack of acknowledging the negative data is a huge problem in academia and often leaves well intentioned hypotheses to linger longer than they should. The reasons are numerous as described in Why don't academics regularly publish their negative results?However, there are new better outlets for publishing these results and with the onset of new low-cost open-access journals like PeerJ and PLoS One, the barriers toward publication are being reduced. Ultimately it will take a massive culture change before that happens.GSK and others have also recognized that lack of data sharing in Clinical trials have also hindered their ability to predict potential failures. Unfortunately, the current situation is a prisoner's dilemma where companies that share the data get hurt by the companies that don't but all of the companies would greatly benefit if everyone shares. However, through outside political pressure from the NIH and FDA along with internal pressure, this should be a dilemma that gets resolved as the inertia changes. [20] You can find out more at All Trials Registered. There is also an extensive discussion by Ben Goldacre that is summarized in What do medics, researchers, drug company employees or drug regulators think about 'Bad Pharma'?There currently is a lot of valuable data out there. Genome sequencing has open the floodgates in genotype information and doctors see interesting observations all the time. However, there isn't an efficient system capturing all of this knowledge and despite all of the hate towards the Patient Protection and Affordable Care Act, if it accomplishes anything, it will be the mandated migration to EMRs.The SummaryCongrats. You are approaching the end of this giant tirade about the stiff and stubborn drug making complex. I hope that people understand that there are a lot of factors at play and the high cost of drugs isn't entirely the drug industry's fault. In addition, there are complicated politics that prevent the major players from interacting. Do to this, we need to do a better job passing a compound from one stage to the next.Academics need to do a better job convincing companies of their science.Doctors need to do a better job relying their problems to the academics.Pharma companies need to do a better job funding the researchers.Pharma needs to do a better job designing their trials.The FDA needs to do a better job allow people to design these trials in that manner.Everyone needs to publish their data.At the end of the day, it comes down to having a system where science is relevant to the medicine and guides the drug development process. The industry needs to shift to a system where hitting singles and getting compounds through is more cost effective and efficient than swinging for homeruns. This is a topic that I talk about quite a bit and I suggest following In the Pipeline: and the Quora blog Making Drugs.[1] Diagnosing the decline in pharmaceutical... [Nat Rev Drug Discov. 2012][2] Outsmarting Cancer: Why It's So Tough[3] Druggability[4] Small molecule inhibition of the KRAS-PDEδ interactio... [Nature. 2013][5] The State of the Art of Chemical Biology[6] A critique of the molecular target-based drug disc... [Metab Eng. 2008][7] Osawa and Miyazaki, 2006[8] Organic synthesis toward small-molecule probes and drugs[9] http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020124[10] Believe it or not: how much can we rely ... [Nat Rev Drug Discov. 2011][11] The Sirtuin Saga[12] Thinning the Fog around Sirtuins | Guest Blog, Scientific American Blog Network[13] http://www.sciencemag.org/content/334/6060/1194.full[14] Making Changes Inside Merck's R&D[15] An Outsourcing Blast[16] Translational research: 4 ways to fix the clinical trial[17] How A Failed Alzheimer's Drug Illustrates The Drug Industry's Gambling Problem[18 ] Adaptive Licensing: Taking the Next Step in the Evolution of Drug Approval[19] Discovery of small molecule cancer drugs: successe... [Mol Oncol. 2012][20] GSK commits to publishing all clinical trial results (Wired UK)

NoThis was his video where he predicted a global disaster between November 2019 to April 2020.I am mentioning of some highlights from this video and how people are associating it with Corona crisis.“At 5.14 - Gold prices will see a big hike”He said that gold prices will shoot rapidly around November 4. However, Gold price has already been in uptrend since May 2019 as evident from here. In fact the prices were almost flat from October 1 to December 20. I have been selling stocks and buying Gold since early 2018 waiting for a financial meltdown.“At 5.50- Economic tension will rise.”Economic tension was already on rise between two giant economies China and USA since 2017. There have been ongoing trade wars between USA and Iran and many South East Asian countries.Here’s an article from May 2019 from IMF[1].“At 6.50 - he said 11th January 2020 kaalsarp dosha is there & the first covid-19 death was reported in China was on 11th January as per some random article.”As per COVID-19 pandemic[2]:The first confirmed death was in Wuhan on 9 January 2020.Moreover, the virus has already spread and many people might have already dead. Its death which is a disaster and not the entry of death in books.“At 7.29- he said Saturn to change position on 24th January & massive disaster to happen.January 23: Chinese authorities placed the 11-million-person city of Wuhan under quarantine — and the rest of the Hubei province days later.”First of all the date does not matches here. Anyways, a room for such a minute error can be granted. But, what is the comparison between quarantine and massive disaster? Is quarantine a disaster or is it to prevent one?. Also, he said something water. May be he meant a Tsunami, flood or naval attacks. Not sure though.“At 8.33 - mars & saturn conjunction at March 31st. Disaster during that period.”First of all he mentions of disaster compared to bombings of Hiroshima and Nagasaki. Covid by March 31st has not reached that scale.As per the graph there were close to 45000 deaths by March 31st. While the bombings of Hiroshima and Nagasaki[3] killed over 200,000 people in the same time span. His predictions were more aligned to war like situation and I will come back to it later.Second, death rate has been steadily on rise since many countries which is how a disease (and so its deceased) expands exponentially. March 31st saw less than 5000 deaths while April 17 close to 8500. Worst is yet to come.[4]“At 9.19- Air India, aeroplane, autmobile and motorcycle industry will be severely affected.”Air India was on the verge of getting defunct since 2018.[5]Jet Airways crisis[6] also began in 2018 as evident from its stock continued downtrend.Now, returning to war thing. His expectation was war and his predictions are aligned to it. Historically, crude has gone up during wars. And it is a well known fact that Crude Oil prices rise affects airlines industry a lot. Indigo 2018 Q2 loss stood at 652 Crores on 84% surge in fuel cost.[7]However, amid corona crisis crude oil prices has shrinked to levels of 1947 because on almost no demand amid lockdown. WTI oil futures even went into negative territory for the first time.[8]Coming to Automobile Industry. Automobile industry has been into shambles since 2018 as evident from Nifty Auto Index:The downcycle is due to many reasons like government regulations on design of trucks and load carrying capacity (which meant heavy axles and reduce in margins), irrational targets for electrical vehicles(they even announce 100% by 2030 once and have revised targets to 30%[9]), industry cycle in case of commercial vehicles like motorcycles and four wheelers and as per our FM Nirmala Sitharaman millenials using Ola and Uber.[10]Let me take you through financials of few Auto sector giants:Maruti Suzuki(Commercial Light Weight Vehicles)[11]You can see a 35% decline in PAT(Profit After Tax) from Sep 2018 to Dec 2018. The PAT has not even recovered as of Dec 2019 quarter despite of lower % taxes in Sep 2019.Eicher Motors(Commerical Heavy Vehicles, Trucks)[12]The sales peaked in Jun 2018 and has not recovered yet. PAT though has recovered in Sep 2019 particularly because EIcher Motors also sells luxury bikes and tax reduced drastically. If tax would have been paid as in Jun 2019, PAT would have been close to 475 Crore.Hero Motocorp (Motorcycles)[13]There has been a steep decline from Jun 2019 to Sep 2019 quarter. Sales went from 8186 crore to 7660 crore while PAT declined by 30%. Also motorcycle business did not take a very deep hit.“At 10.35- **there will be widespread disease or virus**”This prediction gave me chills. But still possible if one analyze things properly.First, many epidemic outbreaks have already happened. Sars has already emerged from China and the movie Contagion(2011) has eerie similarities with the present corona crisis[14] like its origin in China with a virus leaping into humans from a Pig to a Bat and then to a human. Such viruses are called Zoonotic[15] viruses.Also, China is already a known hot bed for viral infections as per this. African viruses have actually lower spread rate like Ebola while Chinese viruses have higher spread rate. There is an inverse relation between the lethal action of virus and its spread rate.[16] Chinese viruses usually have evolved for the middleground.Moreover WHO issues a warning in its September 2019 health report[17]:From the report:Moreover, wars pandemics are the most frequent ways that take a huge toll on human life. The last major asteroid impact happened over 50000 years ago[18] while the last pandemic hit globe 100 years back and last global war was fought 75 years ago.To everyone following news, war was the most common possibility since global tensions have been mounting since 2016. He did a masterstroke by mentioning of an epidemic. Since, asteroid things are detected by scientists in advance so no doubt it was easy to rule that out.Also, the pandemic seems unstoppable and only solutions that might stop it are drug, vaccine or herd immunity (took two years in 1918 for Spanish Flu[19] killing 25 million people). Fortunately, medical science is far ahead today.“At 12.23- china will be badly affected.At 12.45 ** the main country being china**”China will be affected because it is the second largest economy in the world as per here[20]. Large economies have lot to loose during a crisis.However, is China really suffering to that extent like America and other European countries? Well, I don’t trust their numbers. But, I have two friends in China one in Hong Kong and the other in Shanghai and they have told me that China has taken very commendable measures to contain the virus. They have now even opened their economy:'Liberation' as Wuhan's coronavirus lockdown ends after 76 daysAnd tourism:Millions travel in China during May Day holidays as tourism, travel open upAnd strategic investments by China and into China:China's central bank buys 1% stake in HDFCIs Italy’s Economic Crisis an Opportunity for China?China’s health, infrastructure stocks lure global bargain hunters amid rout3 Reasons Foreign Investors Should Stick with China amid the CoronavirusIn fact it scared the entire world and they changed their policies against foreign investment:As global economies dwindle, world wakes up to China’s hostile takeovers amid pandemicCoronavirus: India plugs loophole in Chinese 'opportunistic takeover' of firms; govt nod mustHowever, it is too early to say China will control the world order. And if China intends to do so there will be a global war.“At 13.33- rich countries will be severly affected.”During a global crisis rich countries suffer a lot (or the countries who come their way). During WW2, USA, UK, Russia, Japan, Germany suffered a lot when compared to India and China(they also suffered but not as severely as rich western countries). Simple. Rich countries has more to lose. Now, China is also a rich country and the most notorious too(perhaps the Germany of WW2).There can be different outlook to this:Westerers and Europeans have weaker immunity when compared to Africans and Indians.Europeans, Africans have different immune systems, and Neanderthals are partly to thankFrom the article:The researchers also found that differences between populations have been selected for over time because they conferred advantages to people facing distinct health challenges in the places where they lived. As a result, according to the new evidence, people of African ancestry generally show stronger immune responses than Europeans do.This is also evident from history. Spaniards killed Incas in Peru with the germs they brought from Europe who were isolated and does not have resistance to germs. Britishers killed isolated native americans by importing pathogens from African slaves. In fact there is a very beautiful book written over how conquerers killed others: Guns, Germs, and SteelPoor countries might not have strong medical infrastructure[21] and so they might have not increased their testing capacity or done late[22]. India has doubled its testing capacity in last week which also doubled the number of cases. May be we have not conducted enough tests per million likee USA, Italy, Germany, Spain or France. For all these countries tests/million population lies in the range of 20000–40000 while for India it is still 1042. Only a possibility to ponder over. Might be we may have a greater impact which we will realize later.“At 13.55- everyone need to do something globally to save people. Dangerous situation.”This is what we expect from humans and this is what humans around the world are doing. This is what US intended to do when it entered the WW2[23] as Hitler wrecked havoc on Europe and even on its allies like Russia.They are working on testing kits, vaccine, drugs, softwares to fight this crisis hard. And India is also contributing good in this regard.Plasma therapy no vaccine but finally a cure for Covid-19?Mylab ships first batch of Covid-19 test kits to government, private labs - ET HealthWorldIIT professor develops software to detect COVID-19 within 5 seconds using X-ray scanDetect COVID-19 in as Little as 5 MinutesIsrael claims big breakthrough - says it has developed antibody against Coronavirus!Italy claims to develop first COVID-19 vaccineU.K. Starts Oxford Coronavirus Vaccine Trial as Germany Green-Lights BioNTech and PfizerGilead’s Investigational Antiviral Remdesivir Receives U.S. Food and Drug Administration Emergency Use Authorization for the Treatment of COVID-19Chinese scientists identify two antibodies for potential coronavirus drugJapanese flu drug 'clearly effective' in treating coronavirus, says China“At 14.15: solution- faith in God.”I have faith in God. This is how they look like:Please see that a number of his predictions are wrong or misaligned. Anyone following news could have made such conclusions. I went through some of his other videos too and his earlier predictions have been also wrong. He has been also swinging on dates pertaining to when Corona virus may be ending. His prediction about oil prices have been wrong too.I don’t reject Astrology neither I believe in it. But his predictions are something that matched mine since I follow news actively and do a lot of investment research. I think I got all of them right (or weong where he was wrong) except the pandemic thing. I wish I have watched Contagion before.Footnotes[1] The Impact of US-China Trade Tensions[2] COVID-19 pandemic - Wikipedia[3] Atomic bombings of Hiroshima and Nagasaki - Wikipedia[4] ‘Expect Covid-19 to peak around June-July in India, the way cases are increasing’: AIIMS director[5] Govt does not want Air India to go defunct like Kingfisher Airlines, says Ashok Gajapathi Raju - Firstpost[6] Jet Airways Crisis Explained In 10 Points[7] IndiGo Q2 loss at Rs 652 crore on 84% surge in fuel cost[8] WTI crude price goes negative for the first time in history[9] Government finally wakes up: Sets a realistic goal of 30% electric vehicles by 2030 from existing 100% target[10] Millennial mindset of using Ola, Uber adversely affecting auto sector, says Sitharaman[11] Maruti Suzuki India Ltd[12] Eicher Motors Ltd[13] Hero MotoCorp Ltd[14] Eerie similarities between movie Contagion and coronavirus outbreak[15] Zoonotic Diseases[16] How Bad Will the Coronavirus Outbreak Get? Here Are 6 Key Factors[17] https://apps.who.int/gpmb/assets/annual_report/GPMB_annualreport_2019.pdf[18] Mystery of Arizona's Meteor Crater Solved[19] Spanish flu - Wikipedia[20] List of countries by GDP (nominal) - Wikipedia[21] Testing For Coronavirus - Can Latin America and Africa Build Upon The Asian Model?      - Health Policy Watch[22] Why Africa's coronavirus outbreak appears slower than anticipated[23] America and WW2: when, how and why did the US get involved, and why they didn’t enter sooner?