tag:blogger.com,1999:blog-9633767.post6405377178863961692..comments2024-03-25T09:11:17.877-07:00Comments on The Curious Wavefunction: Again, drug design and airplane design are not the sameWavefunctionhttp://www.blogger.com/profile/14993805391653267639noreply@blogger.comBlogger10125tag:blogger.com,1999:blog-9633767.post-16004005366175131112012-09-11T10:52:10.381-07:002012-09-11T10:52:10.381-07:00Completely agree. Although Med chem campaigns are ...Completely agree. Although Med chem campaigns are hardly holistic in terms of the SAR they want to address, likening drug development to that of air craft is belittling the wonderful complexity of life itself. If biological systems were less complex, drug discovery would have been easier and by that token all life would have been wiped out from the planet long back. It is the complexity that helps life survive all odds, so what if it makes drug discovery tough. We'll take it.manmeramhttps://www.blogger.com/profile/11227563598514883853noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-2532775130189530182012-08-21T06:29:11.411-07:002012-08-21T06:29:11.411-07:00That's correct, the liability and reward aspec...That's correct, the liability and reward aspects are often underemphasized. And I think it's precisely this fuzzy assessment of rewards that leads drugs to sometimes be unfairly (in my opinion) withdrawn from the market. I do think that way about Vioxx for instance.Wavefunctionhttps://www.blogger.com/profile/14993805391653267639noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-58728101212669412682012-08-18T15:55:05.434-07:002012-08-18T15:55:05.434-07:00If Hawk-Eye misses a shot, people are unhappy and ...If Hawk-Eye misses a shot, people are unhappy and money might even change hands if it's important enough.<br /><br />If toxicological studies (for example) misassign the risk of a new drug, people could die, either from taking the drug and dying of something they would not have had otherwise or dying from a disease from which the drug which failed falsely could have saved them. There are plenty of other possible mistakes, most of which are likely to be costly.<br /><br />Risk-reward is a concept not well publicized to drug users, and is difficult for any of the many groups in the field to accurately assess. You might be able to assess the risk of a drug, but reward is probably going to be specific to each user, and dependent on emotions and other factors not predictable from first principles.<br /><br />If the key inputs to drug approval are not only highly fault-intolerant but also poorly quantifiable, people are likely to be loath to change anything for fear of what could happen. We do overestimate the cost of mistakes, though, and it is a caveat that not adopting good technology for drug development and approval also costs lives - but there is a big barrier to surmount.Hapnoreply@blogger.comtag:blogger.com,1999:blog-9633767.post-40662105296238200322012-08-15T10:30:33.689-07:002012-08-15T10:30:33.689-07:00I would be surprised if they are not regulated at ...I would be surprised if they are not regulated at all although it's clear that the differences are vast. I found it remarkable that the Boeing 777 was the first airplane to be completely designed on a computer. In 1995. You are quite right about not being able to measure drug levels in real time, a fact that may be responsible for many of our woes including complex clearance and distribution events.Wavefunctionhttps://www.blogger.com/profile/14993805391653267639noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-68675859564389790782012-08-14T19:50:36.952-07:002012-08-14T19:50:36.952-07:00I'm not sure that aircraft manufacturers are a...I'm not sure that aircraft manufacturers are actually regulated and that might be one reason that for the differences. Also I don't think we actually design drugs and that might be another reason for the differences. It is also worth remembering (and reminding the systems biology folk) that it is not generally feasible to measure physiologically-relevant concentrations of drugs in live humans unless the targets are directly exposed to blood. I looked at some of this in a blog post last year: http://fbdd-lit.blogspot.in/2011/09/dans-la-merde.htmlPeter Kennyhttps://www.blogger.com/profile/12180360326821860667noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-77222290673684374372012-08-10T14:47:23.282-07:002012-08-10T14:47:23.282-07:00"Cost to benefit ratio" is a subject in ..."Cost to benefit ratio" is a subject in itself. It makes Drug Regulation (DR) a complex affair. Less predictive nature of biology makes DR more of philosophy than just a quantitative science. This can be fairly illustrated from example of drug "thalidomide" which was withdrawn as a sedative due to side-effects of inducing phocomelia. However, same molecule is used nowadays for treatment of a skin disorder called ENL. Pharmaceutical companies have witnessed several such cases in history. <br /><br />On the other hand, airplanes cannot be used for some other purpose, ones they are proved to be a failure for public safety.Anonymoushttps://www.blogger.com/profile/11363603927414414911noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-26415478138981703682012-08-10T06:25:06.449-07:002012-08-10T06:25:06.449-07:00Either physics or - in Rutherford's words - st...Either physics or - in Rutherford's words - stamp collecting. Given its complexities I am leaning toward the latter...Wavefunctionhttps://www.blogger.com/profile/14993805391653267639noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-17105663621097304832012-08-10T06:24:22.543-07:002012-08-10T06:24:22.543-07:00Yes, as you indicated there are no easy answers he...Yes, as you indicated there are no easy answers here, but don't you feel it's difficult to contrast the heart attacks caused by Vioxx with the millions who were living a pain-free life? I am not saying that the withdrawal decision was premature, only that these issues are indeed thorny.Wavefunctionhttps://www.blogger.com/profile/14993805391653267639noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-89163189848019319702012-08-09T20:21:38.334-07:002012-08-09T20:21:38.334-07:00I've worked in regulatory for both pharmaceuti...I've worked in regulatory for both pharmaceuticals and research-only companies and I am aware of some of the frustrations of regulatory affairs. The concern with cost/benefit related to strict compliance with the rules sometimes results in lost business.<br /><br />While it would propel business forward to lessen the regulatory requirements in pharmaceuticals I keep thinking of medications in which safety concerns were not caught in the clinical trials. How would I feel if someone in my family were affected by Vioxx? Clearly regulatory affairs failed the market in this case- we didn't know the adverse events well enough when it was released on the market.<br /><br />I'm also aware of how sometimes regulations become out-of-date or are irrelevant to particular situations. It is frustrating to spend time tracking something on a spreadsheet that is just busywork- not relevant but required by law. This is a waste of effort and makes everybody want to ignore regulatory affairs.<br /><br />There are no easy answers here..... lessen the requirements and suffer from adverse events (with a booming business culture). Increase the requirements and thwart the progress of science....but definitely fewer risky drugs on the market!<br />Hot topic to write about here Ash- thanks for your thoughts!Juliehttps://www.blogger.com/profile/00340547422474716630noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-42212159639775128412012-08-09T13:01:50.653-07:002012-08-09T13:01:50.653-07:00"For Hawk-Eye to track tennis balls is a simp..."For Hawk-Eye to track tennis balls is a simple matter of physics..."<br /><br />...and what is biology, of course, than a simple matter of physics? ;-)Chemjobberhttps://www.blogger.com/profile/15932113680515602275noreply@blogger.com