Disruptive Strategies for Removing Drug Discovery Bottlenecks – My experiences of a closed access publisher

I felt like I have just stepped into something new.

Last December 23rd I and my fellow co-authors submitted a policy forum to SCIENCE.

Disruptive Strategies for Removing Drug Discovery Bottlenecks

Sean Ekins, Chris L. Waller, Mary P. Bradley  and Antony J. Williams

We felt this was a timely and important- here is the cover letter which explains some of our topics discussed.

Dear Sir,

Please find enclosed our policy forum “Disruptive Strategies for Removing Drug Discovery Bottlenecks”. This addresses how academic screening centers are taking on the screening that was once the focus of the pharmaceutical industry, yet this is counter-productive. We see public private partnerships happening in Europe but not the USA and this may be a way to surmount the bottleneck that has been created. We address other needs such as release of the data created with public funds, its quality, the need to reward collaboration, and how to find the best collaborators. There are potentially several disruptive nascent efforts in sharing precompetitive computational models and clinical trial data as well as new methods for mining healthcare data. As the healthcare industry has a major role in all our lives we question whether the US government is best serving us by shaping academia in the image of pharma.

Yours sincerely

Sean Ekins, Ph.D., D.Sc.

Here is the abstract as submitted

Drug Discovery is shifting focus from the industry to outside partners and in the process creating new bottlenecks, suggesting the need for a more disruptive overhaul. Technologies like high throughput screening (HTS) have moved to a larger number of academic and institutional laboratories in the US, with little apparent coordination or consideration of the outputs and creating a translational gap. While there have been collaborative public private partnerships in Europe to share pharmaceutical data, the USA has lagged behind. Sharing precompetitive computational models may be the next frontier to provide more confidence in the quality of the leads produced and attract investment. We suggest there needs to be an awareness of what research is going on in the screening centers, more collaboration and coordination. These efforts will shift the focus to finding the best researchers to fund and require a rethink of how to reward their collaborative efforts.

Jan 18th I recieved the following

Manuscript Number:1218399  
Dear Dr. Sean Ekins                                                                                           

Your manuscript is now being sent for in-depth evaluation. When your manuscript comes back from review, we will make a decision on the basis of general interest, technical validity, and our available space. We will inform you of a decision as soon as possible
Carolyn Kyle

I thought this was promising. But weeks went by with no notification. I emailed the editors Feb 2, 14th and 16th with no response. I called and basically found out that the paper went out for review. On the 28th Feb I emailed again and called and was told my comments would be passed on.

Today I received the following note and reviews.

Ref: 1218399

Dear Dr. Ekins:

Thank you for submitting your manuscript “Disruptive Strategies for Removing Drug Discovery Bottlenecks.” We have now received the detailed reviews of your paper. Unfortunately they are not positive enough to support publication of the paper in Science. Although we recognize that you could likely address many of these specific criticisms in a revised manuscript, the overall nature of the reviews is such that the paper would not be able to compete for our limited space. We hope that you find the comments below helpful in preparing the manuscript for submission to another journal.

We are grateful that you gave Science the opportunity to consider your work.


Barbara R. Jasny, Ph.D.

Deputy Editor, Commentary


Reviewer #1

The objective of a “Policy Forum” essay is to present analyses of policy implications of recent scientific results or studies or to discuss the intersection of science and society. This manuscript fits in the second category of science and policy issues. The title is “Disruptive Strategies for Removing Drug Discovery Bottlenecks.” Instead of presenting a cogent set of disruptive strategies for identifying and eliminating specific choke points in the drug discovery process, the text briefly diverges rapidly into partial analyses of a range of issues related to the current state of the pharmaceutical industry. The article lacks focus and does not achieve the goal to suggest solutions to the very important problems facing the pharmaceutical industry.

The analysis begins with a description of the limits of high throughput screening (HTS) and notes that many academice institutions are now actively engaged in HTS. The authors raise a very valid point – how can academia expect to succeed with HTS when big pharma has struggled with the strategy for many years and with far greater available resources. The authors do not propose any disruptive strategies for improving, accelerating, or changing HTS. The discussion largely restates the well known problems associated with HTS approaches.

After the cursory description of HTS problems, the article shifts to a discussion of how results of screening data (good and bad) might be shared more widely to better inform the communities involved in drug discovery. The authors identify the difficult issue of the need to protect intellectual property to preserve future profitability but do not offer a strategy (disruptive or otherwise) for promoting increased collaboration while protecting IP positions. This is indeed an important objective but no strategies or solutions are forthcoming here.

The article then moves on to discuss the importance of collaboration and the need to increase the efficiency of finding productive relationships that will promote research. The theme of the article then shifts focus to efforts to improve data sharing and the efforts of FDA to make historical clinical data available for study.

The summary begins with a bold statement of the obvious: “if we are to remove bottlenecks we need to provide more confidence that lead compounds will have efficacy in vivo and be safe.” The solution offered is to increase sharing of recompetitive data, without suggestions of a strategy for protecting the potential for return on investment. The second major conclusion is that “industry and academia should use computer software to “find the best researchers to fund and collaborators to work with on strategic priorities.” Again, this is a statement of the obvious without any real new proposal of the strategy to achieve the goal.

These arguments lack novelty and fail to provide significant new insight to policy makers. The arguments are difuse and do not culminate in an original synthesis that can guide industry, academia, or policy makers.

Reviewer #2

This commentary reviews the landscape quite adequately, something that has been the subject of many publications.It seems to miss the requirement of all NIH funded initatives to outline data sharing plans and does not describe how intellectual property rules and expectations might be altered to remove barriers to data sharing beteween commercial entities ( again something that others have commented on extensively).For example, the possibilities signalled by collaborations in rare diseases and in common diseases mainly afflicting poorer populations have been cited in Science and many other journals over the past few years.

Aside from a catalog of tools and possibilities however, the commentary is short of innovative solutions that have not been discussed by others elsewhere.

We waited over 2 months for these reviews..What were they doing? So what the heck I sent a response to Barbara.

Dear Barbara,

 Thank you for the reviews to the manuscript.

We do not agree with reviewer one that the article lacks focus. Unfortunately the industry and the NIH are putting all of their eggs into many academic HTS centers, while HTS was not successful in Pharma itself, it is worth repeating this point because that is where future drugs are expected to be derived from. There are also problems here for both quality of data generated and dissemination of data. As we suggested they could “work more closely with CROs and virtual pharmas to do more preclinical and development studies” which these groups do not do frequently. Also if pharma’s shared their computational models this may add more information that would provide confidence in the academic screening data. This does not routinely happen either.

Second as we outlined, collaboration and ways to find collaborators is a major bottleneck and we offered suggestions for this using software to connect researchers and their data.

 Third, perhaps most importantly we suggested how public private partnerships can help remove bottlenecks. Unfortunately these do not seem to be ongoing in the US, and Europe definitely has a lead in this respect.

 Fourth, we also suggested the need for a cross-pharma data sharing consortium to lower the costs associated with clinical trial recruitment and execution of placebo dosing. This has not happened yet.

 Although reviewer two rightly says that NIH funded work has to show a data sharing plan, this is not the same as what we suggest, data sharing should be mandated for anything funded by the NIH.

 Finally as we stated emerging and disruptive technologies are not on the agenda at the NIH and this will hold back progress.

With the limited space available we offered an overview of the problems and as many disruptive solutions as we could. While some of them may not have been new to the reviewers, we do not believe that anyone has suggested using a combination of as many efforts to try to improve the situation with drug discovery. The approach we have seen so far has tried to address individual parts of the process, when in fact there needs to be a complete overhaul. It is time for disruption across the board.

We offered our diverse perspectives to Science on this topic because we feel it is of vital importance to the health of the nation.


Sean Ekins

So we feel the manuscript has been peer reviewed and we do not feel like waiting a few more months or more to submit elsewhere and go through more peer review..It is after all a commentary/ perspective / thought leadership / policy forum piece..

So I have submitted it to the preprint server Nature Preceedings and just in case I have also put it on slideshare. So it will be free and open for all. I am not sure how long Nature Preceedings will take to list but I will update this blog with a link. Decide for yourself whether we are saying anything of value. If someone wants to publish it or commision a more extended review from us just get in touch.

My experience with Science certainly was not encouraging anyway, lets see what this more open approach brings. Based on my recent experiences of peer review at other Journals including Pharmaceutical Research and Molecular Pharmaceutics with it taking over 5 months, I am becoming more convinced that this model is unsustainable. I think it too is undergoing a disruption of its own.

UPDATE. As of today the preprint is now available here at Nature Preceedings.



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