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I don't debate these make it better, but it doesn't seem like they should be required - most of the features are pretty standard!

I also found that extraordinary. With such limited information it is not possible to know if the contacts I have are relevant, and how serious and progressed the company are.

After all if I suggest something I'm putting my reputation (in part) on the line, which I'm not prepared to do without at least understanding this is a serious proposal, and the science being at least superficially credible.

I agree here. Also myfitnesspal doesn't let you easily correct things for being wrong; case in point many products list only the calories for something, and not the macros/nutrients. I often search for something as a proxy for what I made myself, so don't have the stats, but do know it doesn't have 0g protein, 0g fat, and 0g carbs.

Basically it doesn't seem to want to help you flag things to make it better. A collaborative enterprise would.

If runners world are interested, theres probably some way of contacting me through here (I've now idea on the best way) and I am happy to add in to the story with some concrete details. For me it was a long day at the office and not what I wanted (2:54), but at least it's a respectable time which may help their interest too.

Sponsoring races might work, semi-major ones who have a magazine and you can suggest it to, but that's going to cost (I've no idea on your funding, and don't need to know).

The freeone would be an adverotial type approach in something like Runner's World. They're always desperate for content, so delivering it on a plate (happy for my example to be used) they would probably like. Always free to ask.

Then there is the manual option - hitting all the facebook groups that exist, and the twitter, sugges0ting for all races (likely half and full marathons). You are probably too late for Houson Marathon tomorrow, but that's a good one where people will be in the same position.

Ultimately you are relying on word of mouth, but it's how you get that initial buzz!

I forget which app it was, but when in the US for the Boston Marathon this year, my friend and I used one of these systems. It was amazing - we left one set of cards and a phone in a bag the day before, plus clothes. We could then finish the race, go to the shop to get our bag (a chinese health store - they stored it in a back room), and get changed, then go have beers. No need to go back to our hotel (which was near Hopkinton).

It's actually a more legitimate service I think than the likes of uber, as it is anciliary service for more income for small shops (we also bought 'candy' when in the store - a bit more revenue for them), as opposed to people relying on it to make a living.

Your point 2 is very important and what so often gets missed. What is statistically significant may not be clinically significant; throw enough patients at something, especially a surrogate outcome, and you can get p<0.05. The hype hungry media then pick that up based on a press release as a wonderous new treatment for disease X.

The reality is most things are incremental improvements, but few diseases are truely curable. Most cancer drugs we have extend survival (by impressive amounts), or in other conditions manage symptoms. Fundamentally however you will probably still die of the cancer, and will still have the condition, just with an extended course. This is huge, and almost magic... but it isn't the miracle cures people want to share on social media.

Every job ad I've put up since starting my company has had over 100 candidates. 80 of whom are wholly unsuitable and do not send any cover letter. Another 10 don't bother with the cover letter but may have been suitable. All these are instant rejects with no feedback.

The 10 I phone interview I will at least give feedback to, likewise the 3 who we eventually interview.

Given so many no hopers though just clicking apply or sending a generic CV, I'm not surprised the vast majority get no feedback.

The draft of my (part time) PhD thesis uses draw.io to present a flowchart of the findings - hopefully it makes the final cut next year.

Fascinating to hear the other uses, and thankyou for a wonderful and elegant tool!

I'm giving my son a classical education with it. Using Retropi

Every now and then we play "Daddy's games", so he has NES megadrive, and MAME (PacMan mainly). As he starts to master those, I'll add the next generation to it. If we've played some of the same games, hopefully it gives us some form of common framework, and him an interest in how he could code something similar i.e. a gateway in to computers. If he decides he doesn't like it, that's fine too.

So far it's goign well - we set off on the adventure 6 months ago when he was 4. I'll also get another microUSB card and try trhe same with my daughter when she's a bit older (currently she's 2).

If you can find a problem, and solve it, a business is a fantastic way to make an impact!

So as someone working in application of medicines, I'd agree with the comments that say those of us doing these things have learn to make code work, but are not software engineers (and would not claim to be). This means that if you can improve the tools that are used (and don't care about making a return), the leverage would be massive.

I imagine it isn't trivial (otherwise it would have been done by now), but imagine if R was automatically parallel processing; seldom is the code in my field worth figuring out how to make it parallel, but if it was automatically, then a hell of a lot of time would be saved! I know there are two packages that kind of make it work, but so far I've yet to hit a threshold making it worth it (I just leave thigns running overnight).

Abstract from that to projects like Zotero and you can see how you could have an impact on a lot of people by enabling them to do what they do.

... or to accept that the plans were not economically viable as they stand. I'm an economist not a nuclear physicist, but the signal the market is sending is that these plans are not what is needed. Find a way to make the electricity cheaper, or accept the demand isn't there.

Except the strike price used is far above the current market rate, with no real indication that it would reach that level naturally. Describing it as a generous subsidy might not be strictly accurate, but isn't far from the truth.

If the strike price used were the current market rate (or maybe a bit lower), that would seem reasonable to allow a company to have the required long term security knowing the bottom won't fall out from under them, but an implicit subsidy does not seem like a good strategy.

All I can say is if like me you'd bought Energenie MiHomes, you'd have spent half as much working out that you need to think twice becase there are so many bugs that make them not worth using... I seldom hear success stories from us early adopters with smarthome things.

I also have two Nests. Stringify has now shut down (and was buggy/difficult to use), and IFTTT is now losing access to Nest it seems, so I guess that's a real knockback of at least several years for smarthome.

Even when it was all in theory working, the most simple thing was not actually possible - Nest shows you humidity, so when humidity is over 60%, turn on the dehumidifier (I have one upstairs, one downstairs). Such a simple task coudln't be achieved because of about individual problems, and this to me puts the date of solving it back quite a way.

Except for the fact that it's expensive to keep people on HIV meds, thus increasing the value of a cure. And the meds are made by lots of companies in competition - if anyone had science they thought would lead to a cure, they would be all over that straight away.

This also assumes that the only motivation is money, if a researcher came up with a cure for HIV they would become an instantaneous scientific god, immortalised in writing, films, having streets and libraries named after them. They would be a hero. That motivation is pretty powerful for many (not for all of those things, but the be a hero part).

Also the headline is massively misleading - almost immediately they point out that many people don't know their status.

It's been 5 years but I rememeber being in a 2 hour talk (I used to work in vaccines) about the difficulty of coming up with a vaccine for HIV, never mind a cure. It sounded then like it was a long long way off, and we're still only just getting much more simplistic diseases vaccine preventable (malaria is what I'm thinking of, the new vaccine is only marginally effective, which may be enough to cut the cycle of transmission... or may not).

Collaboration - one control arm, 2+ active drugs from multiple companies (why not 6+?). Fewer patients exposed to placebo, less paperwork, same statistical power, more so if you randomise 2:1:1:1:1:1 rather than a standard trial with 1:1 or 2:1

The studies performed are the same ones, but companies submit it to the FDA first, who are more likely to approve, and approve faster than European regulators (the European Medicines Agency, EMA). The FDA are the most permissive regulator is what has been seen in the literature - there was a really good study looking at the same drugs (TKIs) submitted to various agencies (it's not the only one, but is the cleanest):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769667/

As for thalidomide, yep the FDA had an amazing employee who saved a lot of damage being done, and shows exactly why regulators exist, and assess the safety and efficacy before you can sell things!

That's actually a very interesting one, and has been written about at length by a number of medical stats people.

Hopefully I do them justice to their arguments by saying that the benefits from supplements (if any) are tiny - as in a hazard ratio of death is pretty much 1 unless you are actually deficient. Equally however the potential downside of them is pretty much zero - expensive wee is what they can mostly be summarised as. Whilst they may be money wasted, the're mostly benign, save the odd tragic case.

If supplements had the side effects of chemotherapies however, they'd be banned straight away - without evidence of benefit, the risks would be too high.

For a more authoratative take, one of my heroes: http://www.dcscience.net/2013/11/18/we-know-little-about-the...

So I work on the opposite end to discovery, in the interpretation, and estimation of outcomes seen beyond the studies i.e. what impact will the drug have. Applied statistics essentially.

The author is completely right about the raw mechanics of investment decisions (and sometimes they are just that when a pharma company is sizing up buying an asset), but has written up a really thought provoking piece which was interesting to read. Though I deal with time preference every day, I hadn't quite internalised how much influence it had for early spending.

In terms of my experience, very similar, I worked in global HQ for a large pharma company, responsible for my small part of things for 4 products. 2 failed in Phase 2, and the other 2 failed their Phase 3s. I moved to another pharma company where I was focussing on launch products, but every now and then one would disappear off the radar. For other the trial results would come in, and it only worked on half the patients. We expected all these to work - the science was impeccable, the animal models demonstrate a good basis for belief... it just didn't happen. Every drug that works really is a needle in a haystack.

On the making development attracting, I've been forutnate enough to be able to volunteer some of my professional time to a patient group trying to attack the problem in a different way, and make it possible to get medicines commercialised in Duchenne Muscular Dystrophy. The approach is led by a couple of really impressive executives* and is trying to get companies to collaborate to pull together some of the materials the author mentions (rather than all do them in isolation with variable quality). They recently won an award for their work, and thoroughly deserve it. These kind of initiatives are what can really make a difference, and de-risk an area for many companies - the lay of the land is known, and there is high quality understanding of what matters to patietns, and the natural progression of disease. It also means that companies developing medicines can engage to make sure their trial program targets the right patients, and measures the right things. If anyone is interested: https://hercules.duchenneuk.org/publicity

* I say executives because that's what they are, and the role they play. They all have sons with DMD which is their motivation, but that label that doesn't do justice to the amazing work the group does - as an example where there are generic medicines that might help, they are funding trials to find out!

Extending patents wouldn't work that well in his model - as you can see from the graphs it is already discounted crazily (I'd argue for a 6% discount rate, not 8, but it hadly changes the calculus). Besides market exclusivity can often be extended by adding indications and pediatric studies, so they aren't as short as first stated. Plus on some drugs you then get other patents - see inhalers where you have patents on the devices as well as the drugs.

Equally asking to prove safety only... you still have to do the studies, and need a lot of exposure so why not capture outcomes too? I'm not convinced it would be a lot cheaper to omit the outcomes - you still have to recruit the patients, and monitor them. Take HIV, if you don't test blood, you don't know what is happening to patients blood counts, since you have the blood, why not also check for efficacy in viral supression?

Regulatory is also based on benefit:risk, without evidence of benefit, why tolerate any risk? Also how many clinicians would give new drugs with only theoretical efficacy?Hopefully none. All the drugs that fail trials we also think should work, and spend money to prove it! Not to mention the market for pharmaceutical is worldwide, the EMA, Health Canada, Swissmedic and others would throw something out with no evidence of benefit, greatly limiting your market, even in the US.

Are the FDA perfect? No. Are they excellent? Yes. Some of my research touches up against what they do, and my respect for them grows with every interaction. They're also continually improving. The fundamental problem is that we're looking at a 'better than the Beatles' problem https://en.wikipedia.org/wiki/Eroom%27s_law

What might work? More collaboration between companies. If we can enrol one placebo arm, but test 4 active products against it, we cut the costs (and improve the ethics by giving fewer patients placebo). There are a few other minor tweaks too, but it is something we all want to improve, and are trying to do so!

I'd also use corporate bonds for pharma companies (or biotechs, depending on which you are looking at) for the cost of capital, as ultimately that's what debt costs

Fully agree - I work with pharma as an independent (and used to work at GSK & Sanofi before that - effectively medical statistics). I'm currently working on a gene therapy from a biotech, if it works it'll be amazing, and be a semi-cure, holding functionality where it is, but even that isn't a perfect cure.

I've also worked on 2-3 immunotherapies, they again can be amazing and turn previously uncurable cancer to long term survival (of duration unknown), but only in a fraction of patients - to work on them was an honour. Most therapies are incremental improvements, which can make a big difference to patients, but there is still unmet need.

GSK when I was there were explicit, half the drugs they wanted to develop internally, but using the commercial knowledge and experience guiding drugs though trial and approvals, also wanted half of drugs to be invented outside, and be commercialised by a company who knew how to do that!

The people who say pharma don't want cures generally don't understand the industry. A cure is worth more than a chronic treatment, and the article does an excellent job of explaining time preference (his 8% discount) - having a treatment you can sell for more years isn't worth much when you discount it all.

Fundamentally companies have to follow the science. If the science is there for cures, that is what is pursued. If the science is on life extending treatment, that's what gets followed up. You don't get to pick and choose what you want - both can be lucrative, and both can be failures!

This is exactly correct. Also there is a good incentive structure in there - a well designed clinical trial program will move between phases, collect all data possible to support an application, and have all the relevant data to get a timely approval. The better you do on evidence collection, the sooner you are on the market, and more you have to work with

Simple answer is probably not; even a lowering of standards you still need to know if it works - so still doing studies. You'd also then get more drugs like Lily's recently that in post-marketing turns out not to work, but ate of half a billion in sales, and a lot of patients who got not benefit.

There is no simple easy answer, it's a massively hard problem. The regulators have to balance benefit and risk, and for the most part do a hugely impressive job where they already have to add in judgement.

See an example of transport unions in the UK. Tube drivers are in the top 5%/10% of income in the UK, for a 35 hour or so week, and a lot of other benefits. The union power has done amazing things for them... but at a huge cost (albeit dispersed) cost to the rest of society.

Fully agree the ideal is where you have both. Germany seems to have good models where unions improve the efficiency of companies in giving a point of contact for negotiations, and helping the company succeed - winning together.

The problem is you are a small provider, and they are a megacorp. There are alternatives for them (all the other small companies), and the corporate terms are say 90 days. No small provider has the leverage to say no. The terms also just aren't up for negotiation, these are our payment terms.

The best I manage is having projects wherey ou bill half up front, and half on completion (or similar), though some companies also don't allow that.

The onyl time that changes is when terms ae totally ridiculous like GE and the 120 days. At that point it just isn't worth it. One client has annoyed me so much with late payment etc. forms, and just being a pain, that I've refused to deal with them again. It isn't worth the time.