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Drug Development

Gaps Where a Book Might Fit?

So what, in your opinion, are the biggest gaps in knowledge that new people entering drug research have? I ask because I had a request from a publisher, who’s wondering if there’s room for a new title addressing that market. (It may be that the knowledge involved doesn’t fit well into the textbook category, but maybe it does).  And I’d like to expand the question a bit – what areas are there that aren’t well served by any current text? The publisher involved would be glad to hear about these, as no doubt would others. And I’m getting ready for my annual series of posts on book recommendations, etc., so that fits in as well. Suggestions very welcome in the comments!

(Update: I should mention, since some have asked, that this is indeed one of the big reputable publishing outfits).

62 comments on “Gaps Where a Book Might Fit?”

  1. VZ says:

    Speaking as a cell biologist and from my own experience:
    – necessity to think about PK and ADME as soon as possible,
    – necessity to think about transition to in vivo from cell line models,
    – necessity of good statistics.

    Haven’t seen it all covered in one book – usually scattered in many places.

  2. Michael says:

    This may not fit your category, but the Andy Grove Fallacy surely deserves a more in depth exploration.

    1. Kris says:

      Absolutely agree with Michael. Andy Grove fallacy needs be dealt with an unbiased outlook. Yes, drug design is really hard, but there has to be more than few characteristics that we can adopt (quickly) from the computer tech industry that will help us reach our goals quicker and more efficiently.

  3. SoCalToBoston says:

    Building on the recent antibiotics discussion, there are huge hurdles in moving from something that works in a dish to something that works in animals, let alone humans. PK/PD issues are definitely important. However, academic training rarely addresses this.
    Another important and related problem comes from tox. Even if you have a compound that bound biochemically and hit in cellular anti-proliferation, we have a long way to go to weed out potential warts that could crop up in vivo that are completely unrelated. Conversely, I have seen proposals to overcome tox by increasing potency and selectivity when the problem is all but certain to be on-target. Again, this is rarely covered in grad school or post doc work.

  4. Isidore says:

    I assume that you will get as many responses as different areas of research, with each person bemoaning new people’s lack of knowledge in his/her particular area. From my perspective, as an analytical chemist/mass spectrometrist doing peptide and protein work, I think it would be nice if biologists and biochemists had a better understanding of analytical and characterization methods and instrumentation so one does not have to spend too much time educating them on the basics but can move on to more involved discussions. Actually I enjoy talking about what I do and what can be done with the technology and I have frequently offered lunch seminars and such discussing analytical and characterization topics, but a nice book for the particular audience would be quite helpful, in my opinion.

  5. The most needed book is fitting the gap between the table and a receiver flask. 🙂

  6. watcher says:

    How about topics that involve predictable reasons for failure or misalignment. For example, failure would include the lack of understanding of formulating for human use compared to the type of things often used in early pharmacology work. Misalignment would include the lack of appreciation that great biology and a great target does not by itself make a small molecule drug.

    (I’ve just had to explain these examples, yet again, to a group that is enamored with a target and insoluble compounds that have been using terrible formulations to do pharmacology work, and they did not want to believe my comments.)

  7. Mike says:

    In my experience, medicinal chemists newly entering the drug discovery field should be taught that potency against your target is the easy part. Focusing on finding a chemical series that has good drug-like properties (ADME, etc.) early in the process is more important. Building in the required potency later on is generally not difficult.

  8. Kelvin says:

    Fundamentals of risk management, including portfolio and decision theory, probability, statistics, return on investment, etc.

    After all, R&D *is* risk management. Understand risk management, and you’re more likely to ask the right questions (or ask the right people), and take/address the right risks at the right time.

    Everything else is pure chance. 🙂

    1. Chemjobber says:

      Is there a book that you think get close to talking about these issues?

      1. Kelvin says:

        None that I know of, at least none that apply specifically to R&D/drug discovery, and most are virtually unreadable (too mathematical). Daniel Kahneman’s book, Thinking Fast and Slow, is along the right lines.

        Otherwise I have put together one or 2 ppts myself on the topic, hope they help:

        http://www.slideshare.net/KelvinStott/working-with-risk-in-pharma-rd
        http://www.slideshare.net/KelvinStott/kelvin-stott-risk-and-uncertainty

          1. Phil says:

            Agree that Kahneman’s book is a good start on the kind of thinking that will help people understand how to appropriately think about risk in R&D. I would add the “value of information” to Kelvin’s list of concepts that are crucial to risk management in drug discovery research. Sam Savage’s “Flaw of Averages” and Doug Hubbard’s “How to Measure Anything” both address this concept nicely, but again, not in a way that is specific to drug discovery.

          2. Kelvin says:

            Definitely the Value of Information. Also the Black Swan and the Signal and the Noise. But someone really ought to write a book that applies these principles specifically to drug discovery, perhaps illustrated with lots of examples of unexpected outcomes (both good and bad), as suggested below. I think demonstrating the lack of predictability in R&D is a lot more useful than putting too much focus on explaining rules of thumb, because it encourages more exploration and experimentation, and hence innovation.

          3. Phil says:

            Kelvin, I agree. Based on the work you linked in the slideshares, you’re a lot closer to writing one than I am!

    2. Matt says:

      I agree completely with Kelvin! As an early career med chemist I find this topic to be the most important and somewhat difficult to understand. I find that learning biology, PKDM, tox etc. are easier than the business side of R&D. Risk assessment and management would allow me to try and identify the greatest risks for failure and address them as early as possible in the research stage so as to minimize time spent on a project bound to fall short in the near or long term (i.e research/discovery to commercialization). This skill will also be necessary if you ever want to move into management and have to convince your company’s upper management that a project should move forward or not.

  9. Andy II says:

    I would like to have books about:
    – Not successful examples of drug development that covers: disease area, MOA, chemical structure, list of preclinical publications, clinical studies (# patients, endpoints) and efficacy and safety summary, and reason of the failure.

    I have been following and tracking whatever available but my search has limitation. I think it is always nice to have those data for R&D people next generation.

    PS. the math problem is getting harder as I see now multiplication. Wonder if I put a wrong answer in, what would happen…

  10. alchemist says:

    I second the comment on PKPD. Not sure if/how it is adressed in books, but I have seen way too many projects (not only in academia, but also in biotech) with compounds going straight from the cell assay to a disease model, with no understanding if the compound can actually modulate the target at the dose given (no PK, even less PD, and a joyous lack of understanding of the concept of protein binding and free fraction).

  11. anon says:

    How to manage CRO’s in China/India.

  12. Tim Carlton says:

    Only a slightly tangential note, the publishers call reminded me of an article I read in September on the academic book scam. How earnest is your publisher?

    http://www.theguardian.com/higher-education-network/2015/sep/04/academics-are-being-hoodwinked-into-writing-books-nobody-can-buy

  13. Sid says:

    Would be interesting to have a book(s) on industrial drug product development. There are several discipline-specific books available, but they IMO cover only 20% of the story. To have a book providing a more holistic overview of drug development would be quite instructive, not only for budding graduate students, but also for a lot of folks in the industry.

  14. Cellbio says:

    Complimenting the PK/PD and ADME suggestions, the fundamental aspect of concentration driven pharmacology in dynamic systems that clearly lays out concepts like Cmax and AUC as important elements of target pharmacology and toxicology. This will also have to be rooted in binding kinetics as the basics of drug-target interactions are poorly understood. WAY too often otherwise productive researchers think of binding events in terms of stoichometry or for targeted therapies as if the molecules have a personal will to bind the target. I can’t count how many times I have had to use Avogadro’s number to calculate the vanishingly small concentration required to occupy a target site, or describe the basics of a Ki or Kd, noting the requirement that target saturation is not changing ligand concentration. One can also add biological half-lifes of proteins and cells to increase the fun complexity of dosing considerations.

    This discussion would obviously have some relevance for the general public in thinking about “toxin” exposure, and for researchers that screen or dose animals while only measuring desired outcomes. Maybe the book could draw upon some ancient history for a title: Dose Makes the Poison, Pharmacology makes the Drug.

  15. Mark Thorson says:

    Not what you asked for because it wouldn’t be very useful to anybody, but it would be very entertaining. How about a book about oddball compounds?

    Cisplatin is a good example. The first really powerful cancer chemotherapy drug. And there’s a bizarre story behind it. It was discovered by accident when a really stupid idea for an experiment succeeded, but not for the anticipated reasons.

    Lithium in psychiatry is another. It’s a rare example of a drug that was popular, fell out of use, almost forgotten, then made a comeback. The doses they were using in the 1880’s are about the same as used today.

    Some of these drugs have good stories behind them, which could make for enjoyable reading.

  16. Susan says:

    I think VZ hit it. Most academic/newbies in drug dev are pretty good when it comes to synthesis and making more potent cell based inhibitors (lead discovery). However – taking the steps to make something drug-like (not just a “cell killer”) is a black box to many. Help is needed on how to map out the right ADME + PK + PD proof of concept studies. How to prove Mode or Mechanism of Action? Lastly – what do those studies suggest and how might they drive SAR and new compound series?

  17. Ted says:

    Hi all:

    I don’t keep up to speed with the area quite so much anymore, but Repic’s “Principles of Process Research and Chemical Development…” is getting a bit long in the tooth.

    -t

  18. I think a very useful book would be one that talks about how to integrate thinking in drug discovery across various disciplines and prevent yourself from getting billeted in silos of highly specialized knowledge. One of the paradoxes of modern drug discovery is that even as the field becomes more and more multidisciplinary the scientists in it become more and more specialized and master of only one domain.

    I am thinking that a book with a title such as “What Every Drug Discovery Scientist Should Know” would be very useful. Chapters would have titles like “What every drug discovery scientist should know about assays”, “What every drug discovery scientist should know about ADME/PK” etc.

    1. Bagnar says:

      Start writing right now ! I do pre-order it immediatly ! 😉

    2. PharmaNewbie says:

      I agree.

      I have recently moved into pharma from an academic position.
      Since then, I have come across very detailed texts on very specific issues.
      But an overview text discussing various drug development issues in an integrated fashion seems to be lacking (at least, I have not found one yet).

      Start writing and I guess you have two pre-orders in the bag.

  19. luysii says:

    The following is a gap in knowledge that we all have, not just newcomers to the field of drug research and discovery. The protein/protein interface is a huge and tantalizing drug target about which we know relatively little. There are zillions of them in every cell –helping huge macromolecular machines (ribosome, proteasome, mediator, spliceosome, RNA polymerase and general transcription factors) stay together and function. Pathologic examples abound — the senile plaque, the Lewy body etc. etc. For details see https://luysii.wordpress.com/2015/10/12/the-next-big-drug-target-ii/

    1. Crocodile Chuck says:

      + 1

  20. SN says:

    A good textbook appropriate for 4th year undergraduates or 1st year MSc students focused on process chemistry. I think a course on this topic could be excellent, but piecing together various OPRD papers isn’t sufficiently pedagogical.

    1. Chemjobber says:

      Anderson’s “Practical Process Research and Development”?

  21. PorkPieHat says:

    The state of the art in high througput in-vivo screening methodologies (that work).
    But I have to ask, what value are BOOKs for such fast-evolving technologies? Wont they be outdated by the time they’re published?

  22. PorkPieHat says:

    I also think that the importance of choosing the right dose for the target patient population is a HUGE under-discussed problem. A major reason for clinical PoC failure due to lack of efficacy. A book of case studies, esp on failures and successes of similar drugs or even the same drug as a function of dose could be instructional, wherein it describes best practices to identifying proper dose selection. Comes back to what many have been saying about PK/PD in this thread.

  23. Chrispy says:

    Here are a few topics that would be worth covering:

    Case studies in drug discovery: the stories behind how drugs were discovered and developed. An interesting example of this is Happy Accidents: Serendipity in Modern Medical Breakthroughs (now a bargain book on Amazon, I see). This book focuses (as the title would indicate) on the outlandish cases, but it would be interesting to hear the real stories behind “normal” drugs. Also, it would be interesting to hear about efforts that crashed and burned, say in Phase III.

    Therapeutic antibodies: more case studies here. Also, there is a general ignorance about how antibodies are generated (e.g. why has phage been such a disappointment? Why don’t antibodies have predictable PK?)

    Ion channels: This is a daunting field for people new to it.

    Holy grail targets and the failed efforts to hit them. MMPs, p38, RAS take your pick — I’d love a book with a chapter on each!

    Career guidance: This industry can be very rewarding but can also be very difficult to stay employed in. A guide for the aspiring drug discoverer would be useful.

  24. Hap says:

    When are your books coming out?

    1. Kevin Prker says:

      I second that.

  25. Diver dude says:

    Speaking as a clinical pharmacologist, I d say my biggest problem was persuading my early phase development teams to think about developing a drug to treat humans rather than whatever species that was used in the available models.

  26. Casual Observer says:

    Disease models, clinical hypotheses, and all the ways that a high-affinity drug molecule that hits its target with good PK can still turn out to be ineffective. With specific examples, and some discussion of common failure modes.

  27. Christophe Verlinde says:

    For ADME/PK one of the best books out there is:
    KERNS and LI
    Drug-like Properties: Concepts, Structure Design and Methods: from ADME to Toxicity Optimization
    Academic Press, 2008
    552 pages, chock-full of info by real practitioners of the art, now for about $80.

  28. John Wayne says:

    Lots of good suggestions here; I’ll add one that is a little too real: how to know the company you work for is done and it’s time to get a new job. I had to learn this the hard way.

  29. z says:

    Things I Won’t Work With

    😛

  30. z says:

    More on topic:

    How to recognize failures

    or more bluntly:

    How to recognize your biases on the success/importance of your projects

  31. Mark Thorson says:

    Now that I think about it some more, case histories are not a bad vehicle for education — they are widely used in medicine and law for that purpose. Being entertaining helps the reader plow through the education. A couple more examples would be artemisinin which was described as an anti-malarial in ancient Chinese medical books, researched in Mao’s China, and ultimately made it to clinical use as part of combination therapy. Another example would be paclitaxel found during a screening program in the Pacific yew tree, then developed for production using a rather complex plant and fungal cell suspension culture method, and then developed into the improved semi-synthetic derivative docetaxel. Yet another example would be trabectedin found during a screening program of marine products in the sea squirt, initially developed for production in a large-scale sea squirt farming operation (ha!), but then developed into a more practical production method using bacteria to make a precursor and synthetic chemistry to complete the process. Salvarsan is interesting because the arsenicals might make a comeback one of these days, and because its true structure was not known until nearly 100 years after its first synthesis. There’s lots of really interesting stories out there, and they can be used to illustrate important educational points. If they were cool enough stories, maybe The New Yorker would serialize them like they did in their original Annals of Medicine series.

    1. Dave Newman says:

      The story (stories) behind taxol have been given in a variety of reviews mainly from people at NCI’s Natural Products Branch who were involved in it from the get-go. Likewise the stories on Yondelis were given by Carmen Cuevas in Natural Product Reports and that of Halaven in the same journal by Melvin Yu who ran the original chemistry.

  32. CMCguy says:

    Because frequently happens as fragmented approach where info may already exists in a few good references most people rarely get exposed to or maybe people receive via in-house training but often first bit of worthwhile re-education might be on “Lab Safety- what school did not teach you (or even mislead you on)”

  33. Shanedorf says:

    I’ll echo the comments on PK/PD and add PBPK modeling & biosimulation

  34. Mark Thorson says:

    Nice quote from this article about Salvarsan:
    http://pubs.acs.org/cen/coverstory/83/8325/8325salvarsan.html

    “The drug made its way to the clinic with speed unheard of in this day and age: Discovered in the fall of 1909, Salvarsan was in clinical use by 1910.”

  35. SRSchow says:

    I would like to second the call for a book on detailed case histories, including insider’s views, and analyses of drug programs that failed to go forward at the various stages of development. These are very difficult to find. When I give talks about these things, I am left looking back over my now ended career for such examples of drug leads that did not go forward at the discovery stage, development candidate declaration stage, or failed in preclinical development, or failed in Phase 1, 2 or 3, or failed to get FDA approval. A book with lots of these examples and the human stories accompanying them would be terrific, that is if these tales from the crypt can be liberated from the dark matter bowels of companies.

    I, too, would like to see a contrarian book on the development successful molecules that violate medicinal chemistry dogma in general and specifically show successful nondrug-like molecules, the ugly drug molecules, the supper low bioavailability drugs, reactive drugs, toxic molecules (i.e., BOTOX), short half-lived drugs, CNS drugs that are too large or protein bound or display the wrong PSA number to access the brain, drugs that display no PK-PD correlation, drugs that would not pass today’s safety standards but saved a lot of lives, etc. You know, the real world drugs that make the drugs-by-rules, RO5/3, the drug-like molecules and must-have good ADMET worshippers uncomfortable.

    Finally and most importantly, I would like to see a how-to formulation book for medicinal chemists and biologists. I am constantly being asked about laboratory formulations for bioassays, pharmacology studies and safety/tox studies. In the past I just would ask my 75 year old technician to prepare one and like magic an animal acceptable formulation of our difficult drug would appear, but she never explained to me how she did it. I guess magicians don’t tell.

    What are viable alternatives to DMSO? What are useful formulation excipients for formulation drugs for biology/pharmacology studies? What is the logic tree the formulation jockey’s use to identify biocompatible formulations for injection/IP, S.C. or PO dosing in animals. Is there a listing of these acceptable excipients with detailed discussions of the good, bad and ugly properties of each, and the what and why they can or can’t be mixed? What are the limits in using a particular excipient. What is the strategy to create a dosage form for a lead that is brick-dust. What if I need do cell/tissue or animal studies and need a formulation that will not cause confounding results? How is a successful formulation evaluated/analyzed? What are the tricks of the trade? Show me lots of examples of successes and problems overcome.
    Of all the topics, this is the greatest black-box for me, and we need a good how-to reference book. The book: Handbook of Pharmaceutical Salts – Properties, Selection and Use, ed. Stahl and Wermuth is an excellent example to ape.

    As for the requests for books on ADME and drug-like properties, there are actually a lot of excellent volumes on these topics, almost as many as on Combichem (and yes you can infer an editorial comment).

    I suggest looking at the following excellent volumes:
    Evaluation of Drug Candidates for Preclinical Development, ed. Han, Davis and Wang, Wiley 2010
    Early Drug Development, ed. Cayen, Wiley 2010
    Hit and Lead Profiling, ed. Faller and Urban, Wiley 2009
    Lead Optimization for Medicinal Chemists, Dorwald, Wiley 2012
    Drug-like Properties: Concepts, Structure Design and Methods, Kerns and Di, Academic Press 2008
    Pharmaceutical Profiling in Drug Discovery or Lead Selection, ed. Borchardt, et.al., AAPS Press 2004
    Optimizing the Drug-Like Properties of Leads in Drug Discovery, ed. Borchardt, et.al., AAPS Press 2006
    Pharmacokinetics and Metabolism in Drug Design, 3rd edition, ed. Smith, et.al., Wiley 2012
    Pharmacokinetic Profiling in Drug Research, ed. Testa, et.al, Wiley-VCH 2006
    ANMET for Medicinal Chemists a Practical Guide, ed. Tsaioun and Kates, Wiley 2011
    Drug Bioavailability, 2nd edition, ed. van de Waterbeemd and Testa, Wiley 2009
    Blood-Brain Barrier in Drug Discovery, ed. Di and Kerns, Wiley 2015
    ADME-Enabling Technologies in Drug Design and Development, ed. Zhang and Surapaneni, Wiley 2012
    Absorption and Drug Development, 2nd edition, Avdeef, Wiley 2012
    The Blood Brain Barrier (BBB), ed. Fricker, et.al. Springer 2014
    Oral Bioavailability, ed. Hu and Li, Wiley 2011
    Drug Transporters, 2nd edition, ed. You and Morris, Wiley 2014
    Drug Metabolism, ed. Kirchmair, Wiley 2014
    Predictive Toxicology, ed. Pfannkuch and Suter-Dick, Wiley 2015
    Drug Safety Evaluation, 2nd edition, Gad, Wiley 2009
    Drug Metabolism in Drug Design and Development, ed. Zhang, et.al. Wiley, 2008
    Metabolism, Pharmacokinetics and Toxicity of Functional Groups, ed. Smith, RSC Publishing 2010
    Reactive Drug Metabolites, ed. Kalgutkar, et.al. Wiley 2012
    Metabolism of Drugs and Other Xenobiotics, ed. Anzenbacher and Zanger, Wiley-VCH 2012
    The Biochemistry of Drug Metabolism, in two volumes, Testa and Kramer, Wiley-VCH 2008
    Discovering and Developing Molecules with Optimal Drug-like Properties, ed. Templeton, et.al., Springer 2015
    Predictive ADMET, ed. Wang and Urban, Wiley 2014
    Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays, ed. Vogel, Springer 2006

    Likewise there are many newer volumes on process development including case histories, but for a beginner in the field, you cannot go wrong starting with the excellent volume by Neal Anderson – Practical Process Research and development: A Guide for Organic Chemists, Academic Press 2012 edition

    For people just entering the field of drug R&D, the must-read volumes are:

    Real World Drug Discovery, by Rydzewski
    The Practice of Medicinal Chemistry, 3rd edition by the great medicinal chemist Camille Wermuth

    There are several hundred volumes that focus on various aspects of drug R&D, including volumes with case histories of drug successes and multivolume comprehensive surveys of drug R&D available in libraries. Plus there are a lot of great older text books on drug R&D with long forgotten insights that one might find useful even today.

  36. Kevin Parker says:

    How about bioinformatics?

    Projecting out 10-20 years, drug R&D may look very different. Those versed in systems biology, modelling, and data analysis will be the most valuable. It seems underserved today.

    I suppose machine intelligence should be thrown in as well.

  37. Charles U. Farley says:

    Statistics, or “How to use and love error bars: The Chemist’s Primer”

    /nuff said

    1. NJBiologist says:

      Take a look at Harvey Motulsky’s latest, Essential Biostatistics: A Nonmathematical Approach. It’s designed to be accessible, which also makes it a pretty quick read (you could probably knock off a chapter after lunch, and have the book read in a few weeks).

  38. Benonymus says:

    I teach an undergraduate med chem course. I would like to see a series of small bite size books (like the old Oxford chemistry primers) of 30-70 pages on key topics in med chem/drug discovery. Molecular interactions, physchem properties and absorption, metabolism, in silico methods… Maybe I should just write one. Standard med chem texts are too big, bulky, impenetrable. And often out of date (“new” case studies from 1980s…you know who you are, textbook). Although kerns and Di is great and thoroughly recommended for the adme stuff, a 50page version for undergraduates and newbies might be good?

    1. I would be interested in discussing your idea further. I work for a credible publisher (not like the one highlighted in the article posted above) and would be keen to see whether we could develop a series of books as you describe. Can you get in touch with me via LinkedIn?

  39. Erebus says:

    Something out of left-field: Formulation chemistry.

    Elka Touitou’s “Enhancement in Drug Delivery” and Pensé-Lhéritier’s “Formulation” are really the only two modern books on the subject — at least insofar as I can tell! — and they’re both very partial and incomplete. I don’t think that there’s a single book which offers a complete overview of the current state of the art in formulation chemistry. (Especially with respect to formulation considerations for proteins and biological drugs, pulmonary drug delivery, nanoparticles and other modern “enhancement” techniques, and the stuff that short reviews tend to leave out.)

    …Are there any good books I’m missing? Or does one need to be written?

  40. Soon-to-be-former BMS person MOLS says:

    Something like a combination of:

    (1) the best comments from this blog ,

    (2) PB Medawar’s classic book Advice to a Young Scientist (published in 1979; handed to me by a grad school professor circa 1986) ,

    (3) Drug-like Properties by Li and Kearns , and

    (4) Up The Organization (1970) by Robert Townsend .

    The biggest lesson a new pharma researcher needs to learn is just how many different issues there are that can sink a drug discovery program, and how easily a Discovery Working Group can paint itself into the proverbial corner by chasing potency alone. You will be part of a team, indeed probably many teams, so you’ll be expected both to offer insights from your specialty (the easy part) AND see how your specialty relates to the others (the part I sometimes had to learn the hard way). Almost without exception, among your current lead molecules, none will be the best by all your metrics and you therefore need to think about trade-offs.

    Unless you’re a chemist yourself, you don’t need to understand all the structural details. But you do need to understand what issues the chemists are trying to address. Only the chemists can make new molecules; everybody else is basically helping them decide what to make.

    If a Senior Vice President asks you in the elevator, “so what’s the biggest issue right now for the Foobar Kinase Inhibitor Program,” every Working Group member should be able to give a succinct reply.

  41. Ann O'Nymous says:

    There are books for the early-career researcher, say, just leaving grad school, and books for the general reader.

    In the first category: a book that covers the process and pitfalls of taking a drug from lead discovery through to market. The tendency (and I don’t say this to slight PIs and their hard-working students) is to think that a brilliant insight into how compound X acts on system Y is the hard part and everything else is reasonably simple: making sure it doesn’t kill people, replicating the synthesis at industrial scale and thinking up a cute name. Educate the reader on the process as it really is (eg how FDA approval *really* works), and point out case studies where things broke down (thalidomide enantiomers, …). Give the reader tools to understand how the pharma business works so they are not worker bees reacting to some suits upstairs but can understand and participate in their own futures.

    For the general reader, I would love to see a spirited defense of the chemistry industry along with acknowledgement that pharma often shoots itself in the foot. Chemical science has given us amazing things. Drug pricing is harder than a soundbite. Shrkeli and co are nut jobs and here’s why. A book that contained all three of those aspects would be a must-read.

    C’mon Dr. Lowe, we’re all waiting on you to hit the word processor.

  42. Jeff says:

    I also second a book of case studies.

    Beyond that I’m more later stage development than most of the other comments. In my new hires and even in people who have been in the field years, I note a huge lack of understanding of bio statistics. There are many people designing trials that will cost millions of dollars but lacking even a basic understanding of the statistics that are behind them. Generally I find this is because the statisticians don’t understand the nuances of clinical development, and the clinical development people’s eyes glaze over when the statisticians start talking math. So my suggestions:

    1. A plain English approach to bio statistics, discussing endpoint variance, missing data handling, covariates, sample size selection/powering, parametric versus non (and general model fitting) impact on results, and the key differences between time to failure, continuous variable, or categorical endpoints.
    2. Not really worth a whole book, but also lacking is expertise on designing EDC/CRFs to maximize clinical information collected. There is a stunning gap between what is collected in studies versus the data you will want to answer those questions which inevitably rise once you start analyzing the results.

    1. diver dude says:

      Biostatistical Analysis by Jerrold H Zar has been saving my sanity for decades.

  43. Scholander says:

    A lot of people are saying case studies, but many Medicinal Chemistry texts are pretty much made up of case studies. I used to teach with Silverman’s “Organic Chemistry of Drug Design and Drug Action”, and I actually had students tell me they were annoyed with the development examples because it was hard for them to glean an MO from them – it was always “they made this 20 or so sequential variations of this compound until they hit one with acceptable potency and PK”. (Which is kind of the point…!) Textbooks may not have the rich, personal history side of things, and I agree that that’s fun to read, but I’m not sure it’s not well-covered already (ala Billion Dollar Molecule).

    Reading about failures – that would be interesting. And I really like CuriousWavefunction’s interdisciplinary idea.

  44. Overthetop says:

    What about a “An Idiot’s Guide to Surviving Endless Rounds of Pharma Layoffs”? There is a huge gap in knowledge here.

  45. Bruce Long says:

    I am a non-chemist. I am an electronic engineer developing new technology and products in a start-up. I don’t have much to add to this conversation but I agree with those who have suggested inclusion of case studies. It is really useful to understand what others have done right, what they have done wrong and when they where just plain (un)lucky.

    It might be possible to write a text so that it addresses two markets. Put enough meat on the bones to address the specific questions of drug development/discovery professionals and make the skeleton large enough through the addition of illustrative case studies for the text to be useful at the other end of the reader spectrum, such as business students and med school students.

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