Rational reform of new drug research and development: Transformation of medicine instead of pipeline mode is the general trend.
2018-4-24 source: unknown clicks: 2 Author: unknown
The new drug research and development in China is in the initial stage. Because most local pharmaceutical companies are still in the stage of "imitation" and "heel", and the property in the R & D pipeline is not rich, the strategy of copying transnational pharmaceutical enterprises is not the best way. For a long time, pipeline development, milestone goals and parallel tasks may still be the best way for local enterprises to improve their efficiency.

(rational reform of new drug research and development: Transformation of medicine instead of pipeline mode is the trend of the times. Photo source: Baidu pictures)

1. Moore's law and the crisis of productivity

In recent decades, almost all the important technologies involved in the development of new drugs have been improved exponentially. The DNA sequencing of new targets was one billion times faster than in 70s; combinatorial chemistry made chemists 800 times more molecules per year than in 80s; the three-dimensional structure of protein was calculated by three orders of magnitude less than the time spent 50 years ago.

In view of this, the productivity of drug research and development should be at the highest point in history.

But the industry's embarrassing reality is that at the same time, drug development was faced with a serious "productivity crisis": candidate drugs were more likely to fail in clinical trials than in 70s; during 1950~2010, the cost of research and development of a new drug doubled every 9 years. This trend was very stable in 60 years... New drugs were developed. This dilemma is called the "Eroom 's Law, the reverse spelling of Moore's law, and Moore's Law means that the performance of a computer chip turns 1 times every 18 months, and the price falls by half).

Since 90s, some scholars have repeatedly proposed the possible explanation of the law of inverted Moore, which can be roughly divided into three conjectures:

(1) drooping fruit hypothesis: the drugs found before are easy to find, and the rest is difficult.

(2) the regulatory obstacle hypothesis: after the reaction stop incident, the regulatory agency's demand for new drug declaration has been increasing, resulting in certain obstacles.

(3) the problem of R & D model. The first two, whether they are objective facts, are difficult to change.

So, where does the R & D model come out?

2. "line factory"

With the development of high throughput screening and combinatorial chemistry in 80 and 90s, and the view that a variety of "omics" can bring a large number of new targets, pharmaceutical companies have set off a trend of change to the R & D model of the "industrial line". In this period, some of the management strategies practiced by the mature and efficient auto industry, such as TOYOTA's "Lean Six Sigma" approach, seemed to give the pharmaceutical industry a trace of inspiration. Many companies are working on similar strategies to improve the efficiency of drug discovery.

The core points of these R & D management strategies include: strict stage division of labor, overall process optimization, shortening cycle, controlling variation, and eliminating delays. However, is this development strategy really suitable for new drug development?

2.1 milestone objective paradox

As the R & D process is strictly divided into different stages, the goal of reaching a milestone in the setup phase seems to be the most direct way of efficiency management. The theoretical basis behind this model is rather rough: if one of the 10 projects that enter clinical trials will succeed, the candidate drugs that will enter the clinical trials will double and eventually get 2 listed drugs.

It is worth noting that there may be an embarrassing fact behind this: in order to achieve a milestone goal, researchers and managers inevitably need to consider meeting quotas and bring some of the bad projects to the next R & D stage. This drive mode of "quantity" actually damages the quality and sustainability of R & D pipelines.

2.2 parallel task paradox

Another important trend in 90s is to decompose each stage of research and development into several parallel tasks, and strive to shorten each cycle. First, we can expect to shorten the whole cycle and secondly, to maximize the duration of patent protection.

In fact, the development of parallel tasks seriously undermines the opportunity for rapid decision-making at each stage. This not only increased meaningless research and development activities, but also made it possible to terminate an unsuccessful molecule for a longer time. Clear data show that sequential strategies are actually more advantageous than parallel tasks for R & D industry with high risk and high wastage.

2.3 Back-up paradox

In order to avoid possible later failures, researchers tend to prepare several similar Back-up for a candidate drug to avoid taking longer time from scratch.

In fact, the current data show that Back-up's strategy basically does not help the success rate, but it consumes resources. Because Back-up has the same structure, the same mechanism and the similar PK as the candidate drugs, it is basically dead.

A lesson for 2.4

2.4.1 "Innovation Studio" or "assembly line factory"?

Pipeline research and development model has been repeatedly questioned in the practice of drug research and development. More and more organizations have realized that drug research and development has its special rules and needs to find the mode suitable for drug research and development itself. For example, the development of a new type of vehicle, a reduction of 0.5 of fuel consumption per hundred kilometers, can be defined as success, and the results of new drug research and development are often "0" or "100".

If it is studied