Considering Compassionate Care and “Right to Try”

Hello Everyone,

For this post I want to transition back to a bit more topical discussion on health and drug discovery.  One of the issues that I’ve been reading about recently, and that you might have been reading about, Is the idea of the “Right to Try” Act that has just been passed.  This act of congress allows terminally ill patients to directly contact drug companies to receive drugs that have passed Phase I FDA clinical trials but do not have full FDA approval.  What’s been weighing on my mind is the thought of whether or not this is a good thing for the patients that it hopes to help.  There are two points that I think we need to discuss with this topic: whether or not there is a need and also whether or not it will work.  It’s hard to see exactly what might happen, if anything, as a result of this act being passed but it brings up the topic of clinical care vs clinical trials which I think we should discuss.

Firs let’s ask the question: “Is there a need for this act”.  According to the “Right to Try” website sponsored by the Goldwater Institute: “Over 1 million Americans die from terminal illness each year” (1).  That seems like a large number!  Furthermore, the Goldwater Institute also claims: “Fewer than 3% of clinically ill patients gain access to investigational treatments through clinical trials”.  Okay so what does this mean?  What’s being said here is that, of that 1 million or so people, only about 30,000 are getting drugs?  Does this mean that, without regulations, all 1 million people could get drugs?  The answer to that is a yes and no.  The writers for the website Biospace looked into the frequency of investigational drugs being given to patients through the current FDA “compassionate use” program.  They noted that “the FDA receives about 1000 annual requests for compassionate use and approves about 99% of the time” (2).  So while the raw numbers may be concerning (1 million people), the cases of terminally ill patients that can actually benefit from investigational drugs may actually be fairly low.

Regardless of the numbers, could these drugs actually help people?  We need to ask ourselves that question.  To answer this we need to think about the fact that we’re taking drugs that have passed Phase 1 FDA clinical trials.  Phase 1 clinical trials in humans means that the drugs will not actively kill or harm you at the doses that are potentially useful.  A recent review paper from Borysowski et al in 2016 summarized the frequency rates of these drugs going all the way through clinical trials.  The authors noted that from a compilation of other studies, “probability of a drug in clinical testing eventually being approved was as low as 11.83%” and furthermore that “lack of efficacy [accounted for] 35.3% of failures”.  This means that 35% of the drugs in these studies, that got past Phase 1 trials, failed because they were not efficacious; they simply did not work.  Still there is a non-zero chance of the drugs actually helping people.  It’s difficult to find information related to patient outcomes related to compassionate use because drug companies are not required to publish that information.  One could imagine however, that there are some cases in which patients have actually been cured by such drugs.

So what’s the verdict on Right to Try legislation?  I think that, as it’s written, the law makes sense and that there’s very little direct risk to patient’s health.  Drugs that pass Phase 1 clinical trials should be mostly safe to use if not particularly effective.  In my personal opinion the main problem comes from an increased blurring of the line between Clinical Care, and Clinical Research.  These are two entirely different things.  Clinical Care means that someone is proscribing you a treatment with the goal of improving your health. Clinical Research means that someone is proscribing you a treatment with the goal of getting a drug through the FDA approval process.  This is why the FDA and review boards exist: to make sure that people realize what they are getting themselves into with a clinical trial.  Now, with Right to Try, we’ve created a weird group that is not quite getting Clinical Care but also explicitly not involved in Clinical Research.  This puts doctors in a bit of a bind as well.  A doctor needs to consider the liability surrounding compassionate use.  They need to think about whether or not they have enough of an understanding of an experimental drug to recommend it to a patient.  This could lead to some grey areas concerning doctors with conflicts of interest such as being involved with the research itself.

In another recent review from 2017, Miller et al make a good point in suggesting that “  Legislative efforts should also aim to expand patient access to clinical trials, which in some cases could alleviate the need for expanded access and compassionate use programs” (4).  Perhaps this is a complementary way forward that we should consider as well.  Expanding patient sign up programs with subsidies, building avenues for patient transport to studies, and increase openness about the efficacy of clinical trials as they are happening could all lead to the same or better outcomes as compassionate use.  Overall, I personally find that this legislation probably provides both little risk but also little benefit.  It’s a good thing that we’re considering the role of regulatory agencies in drug development.  If nothing else we should keep the conversation going.

Thanks again for reading.  Again, I’ll be setting up the lab soon and meeting with new people.  I start sharing those experiences very soon as well!

 

Cheers!

 

GRW

 

  1. Goldwater Institute, 2018, http://righttotry.org/faq/ Accessed 06/01/2018
  2. Biospace, 2018, https://www.biospace.com/article/right-to-try-law-and-fda-face-criticism-from-law-s-author/?utm_campaign=Newsletters&utm_source=hs_email&utm_medium=email&utm_content=63436544&_hsenc=p2ANqtz-8L780WbA4697q2DeSbAg_lzRwrt6_FoPB1q_rky9t7i0HEh967ZID4vXUOTZWLaXlsdvasLuktDSxQVgs_isma6P5MBg&_hsmi=63436544 Accessed 06/01/2018
  3. Borysowski J, et al. Ethics Review in compassionate use. BMC MED, 15:136, 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523146/#CR30
  4. Miller JE et al. Characterizing expanded access and compassionate use programs for experimental drugs. BMC Res Notes 10:350 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534121/
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My Faculty Search is Over

Good News Everyone!

Firstly, I apologize for not updating in a very long time.  As I wrote about before, I’ve been on the hunt for a job in academia for the past year.  I’m happy to let you know that I’ve accepted a tenure track assistant professor position in the Chemistry and Biochemistry Department at Seton Hall University.  I feel extremely lucky to have this opportunity to become a Principal Investigator and teach and train young students to become scientists.  This was the end of a lengthy journey that again was fortunately shorter than most for myself.  I’d like to finally wrap up and share some of my experiences with the interview process and what went into my decision making.

In my search I submitted almost four dozen applications over the past year to departments in everything from Biophysics to Bioengineering to Biochemistry.  I felt that with my background and my goals I would fit well in a department that is focused on life sciences.  I knew that I only wanted to do this if I felt that I’d have a good chance of being able to get grants and support students.  I ended up interviewing at a few universities at both doctoral-granting institutions as well as undergraduate-only institutions.  It was a tough decision, but I ultimately decided that to really be able to ensure support for my students and my work that I had to go to a doctoral-granting institute.

Seton Hall is the ideal place for me to begin my career as an independent PI for a few reasons.  Firstly, the university is expanding and developing a new medical school program.  This opens the door to many clinical collaborations, something that is important to me because I’ve always wanted to do research that directly impacts people’s health.  Second, the university is located very close to my current work at PHRI as well as close to some collaborators at NYU and Columbia University.  I am therefore able to maintain the friendships that I’ve made while working as a postdoc and I’m able to provide even more opportunities to my students.  One final reason that SHU works for me is the atmosphere and the people working in the department.  There are so many places that you could get a job where you’re just filling a seat or a cubical or a desk.  I didn’t feel that way when I interviewed at Seton Hall.  It felt like the faculty and the students were genuinely interested in each other’s work and in helping each other develop their careers.  I’m excited to be able to work with the department and I believe that there’s a lot of room to grow at this place.

I’m so thankful for all of the support and encouragement I’ve received from my friends, family, and colleagues over the past few months.  I’ll try to update this blog more frequently as time goes on with my experiences as a young assistant professor.  In addition, I’ll be developing an official lab website with information on our projects and some of my student’s achievements.  Thank you so much for reading and please keep a lookout for new posts!  If you have any questions please feel free to ask away; I’d be more than happy to help others in their academic job search too!

Sincerely,

GRW

Happy Belated New Year

Hello Everyone,

I’ve been taking some time off from updating to prepare for a few upcoming interviews.  I’d like to mention briefly a few things about what’s expected of a scientist applying for a tenure-track faculty positions.

I’m taking my idea of “Molecular Yoga” on the road and it’s going to influence the first part of my presentation: my “Job Talk”.  Most positions expect you to give them a brief overview of your research interests in an initial Skype interview before they invite you to their campus.  The Job Talk is where I get to tell my story and describe the research goals for my lab.  It has to be both compelling and reasonable; finding the perfect balance is the challenge.  I promise to elaborate more on some of the successes and failures of my job talks in the future once I have some experience!

The second portion of the interview is usually a short teaching tutorial.  I’ve been asked to prepare lectures for specific topics.  I believe a key component here is to demonstrate my ability to 1) analyze a topic that is not directly related to my research, 2) develop learning goals centered on the key components of that topic, and 3) deliver a presentation that helps students achieve those learning goals.  This is, in essence, my chance to prove that I am both a scientist and an educator.  Again I hope to provide a breakdown of what i thought works and does not work as part of an interview in the future.

Thank you all again for reading this quick update.  I’ll be back soon with some more in-depth analysis.

Cheers,

GRW

Into the Fray of Faculty Position Hunting

Hello Everyone,

As I mentioned before about a month ago, I’m beginning my search for a faculty position.  This is my first attempt at looking for positions beyond postdocs so I wanted to give a sense of what I’ve learned and what advice I’ve been given up till now.

Where do you learn about faculty positions to apply for in the first place?  There are three main sources I’ve been using at the moment.

  • The first is through direct contacts. I met search committee members through the ACS Academic Employment Initiative in August and I’ve tried to keep in touch with them via Linkedin or direct email.  This, along with recommendations from colleagues, advisors, and personal friends, is probably the best place to start.  As with any job, getting your foot in the door is the first hurdle.
  • The second source I’m using is HigherEdJobs.com and other academic job listing websites. Here you’ll get a list of recent postings by HR departments at various colleges and universities.  This is nice because you know that these departments are actively recruiting a new faculty member and you get an idea of the timeline for hiring.
  • Finally, I’ve been perusing websites of specific departments from Universities at which I would like to be employed. This, I feel, can be the most difficult and possibly soul-crushing way of doing things.  It’s equivalent to a cold-call almost; you don’t even know if a department has an opening.  That being said, I’ve come to understand that the name of the game is “take every opportunity you can find” and these three sources provide opportunities.

Looking glass

What goes into an application for a faculty position in academia?  First up is the curriculum vitae or C.V. for short.  For those readers who are not in academia, a C.V. is similar to a resume but with heavier focus on academic accomplishments and education/teaching history rather than previous jobs.  These are the most crucial components to an academic position, hence why a C.V. is vastly preferred to a resume (something I might tackle in a later article).

All positions will require a cover letter.  This is where I’ve come to understand most people make their mistakes.  DO NOT use the same exact cover letter for each position.  It may seem tedious at first, but this is the first thing, other than the C.V. that a search committee will read.  The cover letter is a chance to make my elevator pitch for a position, I try to specifically bring up reasons for why I am interested in that position. Also, I make sure to specifically mention WHAT I am applying for: e.g. “I am applying for a position in X Department at Y University”.  I’ve heard a possibly apocryphal story where an otherwise spectacular candidate for NASA was rejected initially because their cover letter was addressed to the wrong agency.

The main body of the application is the Teaching Statement and Research Statement.  Here I’m laying out the evidence to show that I can be a successful faculty member in your department.  The Teaching Statement is a brief description of my Teaching Philosophy (how I approach a class), my experiences in teaching, and finally a brief description of classes which I believe I can teach for a specific department.  Again, DO NOT submit the exact same Teaching Statement for each position, especially in regards to the last point.  It makes no sense to be talking about my willingness to teach molecular biology if I’m applying to a mathematics department.  The Research Statement is my description of a few ideas I have for projects and programs in my new lab.  New faculty are always expected to secure “outside funding”, meaning that after a few years my lab work should be bringing in funding to sustain the lab members.  In many ways it’s like getting a start-up fund to start a new company, for good or for bad.  Knowing that search committees will likely go through hundreds of applications I’ve tailored mine to be 3-4 pages with figures and citations.  I hope that I’ve made it an exciting read and after a while I might even share it here as a templet.

The final components of an application for a faculty position in academia are the references and, at some places, a diversity statement.  The references are straight forward, make sure to ask former/current advisors if they could provide a strong recommendation and testament to your ability to work independently in a lab.  The diversity statement I find most interesting.  Some academics might write off a diversity statement as an unimportant, secondary component of an application.  I, however, think it’s a crucial part of explaining that ever-present, “Broader Impact” that we want to get at as scientists.  Diversity means inclusion in the scientific process.  In general I personally often forget that when I’m conducting research, when I’m making devices; this knowledge or these products are going to be used out in the world.  I’m not just doing this for other scientists like myself, I need to understand the communities that are impacted by my research.  I’ve learned this in Public Health, you need to have feedback and communication with people from all over the world.  Insights from as diverse of a group as possible are absolutely crucial.  This is the point that I stress in my diversity statement: I don’t want to make a small, isolated lab kingdom.  Our lab absolutely needs input and collaboration in the communities which its work is meant to serve which is underdeveloped or economically depressed areas.

These are the components of my application.  If anyone has insights to add or advice I would greatly appreciate it!  I hope that in going through this process for the first time I can get a better idea of what I’m doing and that I’ll have better advice to give in the future.  I will keep everyone updated on the results!  Thanks again for reading!

Cheers,

GRW

Moving on in Science

Hello Everyone,
For this post I wanted to make a brief comment on something that applies not only to science but also to any job in general: knowing when to move on from a particular position. Change is an inherent part of science. As new ideas come about, it becomes time to build upon them and move forward. Sometimes it’s also good to think about when to move on to the next phase of your career. The most successful scientists that I’ve known are able to adapt to changes. I’ve known people who started out in basic electrochemistry and who are now studying cancer biology. I’m always finding myself reading about new labs and new research and thinking “I wish I was working in this field”. I believe it’s that kind of drive, and that kind of enthusiasm that keeps a scientist alive.

For myself, I know I’ve always had to balance my devoting enough time to a particular project and my search for new projects. As I’ve said before, in getting your science funded even, the old joke is that you write a grant to get money for work you’ve already finished while you’re thinking about the next grant. Like anything there are ebbs and flows in science. Sometimes new data seems to be coming in easily and sometimes a direction I’m moving in just feels static. My advice would be to time the “focusing and dedicating time” in a particular area to the ebbs and to start thinking about new ideas during the flows. If I could possibly do so, let me coin the term “Data Drought” in this particular time. A Data Drought, being a time when you are not producing much, is NOT the time to be thinking about something new. That’s how you lose your focus; that’s the “grass is always greener” mentality. This again is broadly applicable; I’d like to think about why I’m not being productive rather than chalk it up to the field I’m in being dead. Again when times are easy and when you’re really productive: that’s the time to start branching out and to start thinking about moving on.

Personally I’ve always felt that the publication of a paper, the finishing of a dissertation, or the completion of a project is the time to starting thinking about what’s next. For me, I’ve just wrapped up several papers and it’s gotten me thinking about smaller side projects that I could complete while looking towards the next phase of my career. I also know that it’s just the type of person that I am; I can never seem to rest on my laurels. I don’t know if that necessarily makes for a happy life but it makes for a good scientist personality. Right now I’m putting together applications and I’ll be going through the process of looking for faculty positions and/or a second postdoc. I hope to write a post in the near future that compares it to my first experience applying for postdoc positions (and to applying for grad school) to give you some insight into the process. Thanks for reading again!

Cheers!

GRW

New Publication: An Aptamer-Based Biosensor for the Azole Class of Antifungal Drugs

Hello Everyone,

I’m excited to announce that our paper finally came out!  This was my first corresponding author paper and also my first decision to publish in an open source journal (meaning you should be able to read it for free).  This work is the culmination of what I’ve been doing for the past 2 years or so at PHRI as an independent researcher.  The patent for it is submitted as well.  Things have changed a lot for me very recently and left me wondering where to go with my career.  I’m considering branching out on my own and sending applications for PI positions to various places.  I’ll keep you all posted on how that process goes as well.

Cheers,

GRW

 

 

http://msphere.asm.org/content/2/4/e00274-17

Nature VS Patent Process

Hello Everyone,

I apologize for holding up my writing this month.  I wanted to mention the reason why: it has to do with submitting a patent for one of my projects.  I thought this would be a good opportunity to explain a little bit of the process as I’ve experienced it.  I had what was almost a 3 hour long conversation with our patent lawyer last week and got a few of the insights into the field of patent law and how it relates specifically to biomolecules.  This is the first time I will do this but I feel it needs mentioning: I AM NOT a patent lawyer myself.  Though you may like my opinions expressed on this blog please do not take any of what I say here as legal advice.

Patent

Patents have always been, and always will be, a source of contention and defensiveness amongst scientists.  You can look back to famous examples such as the long patent battles between Thomas Edison and Nikola Tesla for one example (1).  Another more recent battle that I’ve brought up before is the fight between The University of California at Berkeley and Harvard University over the rights to CRISPr (2).  But perhaps the oldest opponent bioengineers and biochemists have in patent battles is nature itself.  Our patent lawyer explained to me that the first hurdle to clear in patenting a molecule is determining whether or not it could be considered “A Product of Nature”.  This is to say, to some extent, molecules that exist naturally cannot be patented.  Imagine if someone held a patent on the 20 essential amino acids themselves or on the four nucleic acids that make up our DNA!  In my non-legal opinion it’s completely unfair to allow someone to try to claim a patent on something our bodies make naturally.  The ways to get around this involve, for instance, patenting a process to purify these compounds rather than the compounds themselves.  The main point, however, is that to secure a patent you need to make something new or to find a new way to make something old.  If you can prove you are not cheating nature then you get the Intellectual Property; you get to decide who makes this produce or uses this process

The power of Intellectual Property and Patent Law has driven the field of synthetic biology, Big Pharma, and yes, even my “Molecular Yoga”.  Scripps Research Institute points out, “Natural products remain the best sources of drugs and drug leads, and this remains true today despite the fact that many pharmaceutical companies have deemphasized natural products research in favor of HTP screening of combinatorial libraries during the past 2 decades.” (3). Note their use of the phrase “drugs and drug leads.  A drug lead, or more commonly called a lead compound, is a starting point for biomedical researchers.  These molecules can be altered and changed to improve the drugs by way of increasing the drug’s binding strength or decreasing side-effects (4).  As our patent lawyer pointed out: THAT is what you can patent, as long as you can prove that such changes and alterations were not obvious or already present in small quantities in nature.  This is why pharmaceutical companies are focused on screening or rational design of lead compounds; it makes them more easily patentable.

My job, in helping to craft this patent, is to turn what written for an upcoming paper into a set of claims on the patent.  Part my discussion last week was determining what we felt we could claim related to our molecules.  How, specifically do these molecules work?  How are these molecules made?  What variations, if any, can exist?  Biomolecular patents can have dozens, even hundreds of claims.  The goal is to make a patent as broad as possible such that someone cannot easily infringe upon that patent.  Would-be infringers might take your molecule and alter it in some nominal way and claim it as their own work.  If you can secure a patent with strongly enforceable claims, you can make money off of them through licensing, which will help you fund future research

When I started down the road of becoming a scientist I didn’t make patenting my work one of my main goals.  I wanted to create new molecules, things that were useful, but not necessarily things that would make me money.  In my opinion, patenting your molecules should be a means to an end, a way to sustain your research.  There are a few colleagues of mine who’ve made millions of dollars from patenting simple biomolecules.  I imagine it’s hard to prevent yourself from becoming consumed by the drive to make money over the drive to conduct research.  They seem to be doing well though.  They funnel a lot of that money back into their own lab.  This model works especially well for a soft-money driven research facility based on grant-funded rather than tenured positions (something I’d like to go into at a later date).  I was involved in creating another patent as a graduate student, which was subsequently accepted as a provisional patent.  It appears to me that his work will be heading in that direction as well.  I will keep you up to date with my feelings on patents and hopefully this will serve as a good reminder to myself if my views ever change drastically.

Thanks for reading again!

 

Sincerely,

GRW