来自汤诗语的雪球原创专栏

Pharma’s broken business model: An industry on the brink of terminal decline

制药业破产的商业模式：行业已濒临致命的衰退

by kelvin stott — on November 28, 2017 08:44 AM EDT

Updated: 08:56 AM

（作者Kelvin Stott，系诺华制药公司的研发组合投资管理经理）

Like many industries, pharma’s business model fundamentally depends on productive innovation to create value by delivering greater customer benefits. Further, sustainable growth and value creation depend on steady R&D productivity with a positive ROI in order to drive future revenues that can be reinvested back into R&D. In recent years, however, it has become clear that pharma has a serious problem with declining R&D productivity.

像许多行业一样，制药公司的商业模式从根本上依靠有成效的创新，通过为患者提供更多利益而创造价值。此外，可持续的增长和价值的创造依赖于稳定的研发效率和正数的投资回报率，以此方可推动未来的收入，并将收入重新投入研发。然而，近年来，一个现实越来越清晰：制药业在研发效率方面下滑严重，存在着严重的问题。

Various analysts (notably Deloitte and BCG) have tried to measure Big Pharma’s R&D productivity in terms of the internal rate of return (IRR) on investment, but in each case the analysis is highly complex and convoluted (and thus subject to doubt), as it depends on many detailed assumptions and forward-looking forecasts at the individual product level. Here for the first time, I introduce a far simpler, much more robust methodology to calculate pharma’s return on investment in R&D, which is based only on reliable and widely available high-level data on the industry’s actual historic P&L performance. This new analysis confirms the steady decline reported by others, but here I also explore the underlying drivers and make concrete projections, which suggest that the entire industry is on the brink of terminal decline.

很多分析师（主要有德勤和BCG）都试图用投资的内部收益率（IRR）来衡量大型制药公司的研发生产率，但在每个案例里，分析都是高度复杂和令人费解的（因此存在疑问），因为它取决于许多详细的假设和个别产品层面的前瞻性预测。在这里，我首次引入了一种更简单、更健全的方法来计算制药公司在研发方面的投资回报，这种方法以业内真实的历史损益数据为基础，而这些数据非常可靠和详尽，并易于获取。这一新的分析证实了其他分析师的结论，即整个制药行业的处于下滑之中，但在本文中我也探讨了潜在的驱动因素，并做出具体预测：即整个行业已濒临致命的衰退。

A simple new method to measure R&D productivity / IRR

一种测算研发效率/内部收益率（IRR）的简单新方法

Pharma’s business model essentially involves making a series of investments into R&D and then collecting the return on these investments as profits some years later, once the resulting products have reached the market. However, the situation is complicated by the fact that both investments and returns are phased over many years for each product, and not all products make it to market; in fact, most products fail to reach market at all and they fail at different times and costs during their development.

制药公司的业务模式主要包括对研发进行一系列的投入，若干年后，这些产品投放市场时将会产生回报，作为这些投资的利润。然而，由于每种产品的投资和收益都是多年分期付诸实施，也并不是所有的产品都投入市场，情况比较复杂。实际上，绝大多数产品根本不能上市与客户见面，它们会失败在研发的不同阶段，并产生投入成本。

Now we can greatly simplify this picture by considering only the average return on investment across the industry as a whole, which is what interests us in any case. We simply assume that all profits in any given year come from investments made within a single previous year, where the gap between these two years represents the average investment period, from the midpoint of R&D investment to the midpoint of returns at peak sales. As it happens, this average investment period is relatively stable and well-defined, as it is largely driven by a fixed standard patent term of 20 years, as well as a historically stable R&D phase lasting roughly 14 years from start to finish. Thus, the average investment period is about 13 years, from the midpoint of the R&D phase after 7 years, plus another 6 years to reach peak sales before loss of exclusivity.

现在我们可以通过仅考虑行业整体的平均投资回报率来大大简化这一情况，而这也是我们最感兴趣的。我们简单地假设，任意一年的所有利润都来自上一年度的投资，这两年即为平均投资周期，即从研发投入的中期到销售高峰期。恰好，制药企业平均投资周期相对稳定和明确，因为一个新药标准的专利期固定为20年，而且从历史数据看，从始至终的研发周期稳定在约14年左右。因此，平均投资期约13年，从研发阶段的中期后有7年，再加上另外6年来达到销售的高峰期，随后专利到期，排他性保护消失。

There is one potential argument against this method, which is that the later phases of R&D tend to cost many times more than the earlier phases. However, we must also remember that we need to invest in many more projects at the earlier phases than we invest in at the later phases, due to natural attrition within the R&D pipeline. Thus, the total R&D investment is actually distributed quite evenly throughout the development timeline. And, as I show below, the calculated return is not very sensitive to this single assumption in any case.

对这种方法，人们可能会存在一个潜在的争论，那就是一个项目研发后期的支出往往要比研发前期多出许多倍。尽管如此，我们必须记得，我们在前期投入的项目数量要比研发后期多得多，这是研发管线的一个自然属性。因此，总研发投入在整个研发时间表上的实际表现为均匀分布的状态。而且，正如我下面所显示的那样，在任何情况下，计算出的回报对于这个单一假设也不是很敏感。

Before we use this simple method to calculate the return on investment, there is one more small but important detail to remember: The net return on R&D investment includes not only the resulting profits (EBIT), but also the future R&D costs. This is because future R&D spending is anoptional use of profits that result from previous investments.

在我们用这个简单的方法计算投资回报之前，还有一个小而重要的细节需要记住：研发投资的净收益不仅包括由此带来的利润（EBIT），还包括未来的研发成本。这是因为未来的研发支出是以前投资创造的利润的可选用途。

So now we can calculate the average return on investment (IRR) as the compound annual growth in the value of past R&D investments to the value of resulting profits (EBIT) plus future R&D costs, as illustrated here with industry P&L data from EvaluatePharma:

因此，现在我们可以将平均投资回报率（IRR）计算为这三者的年复合增长率：过去的研发投资、由此产生的利润（EBIT）、并加上未来的研发成本，如下图所示，来自EvaluatePharma的行业损益数据：

Now we get the following simple formula to calculate the Internal Rate of Return (IRR) on pharma R&D in any given year x:

现在我们得到以下一个简单的公式来计算任何一年制药企业研发的内部收益率（IRR）x：

IRR(x) = [ (EBIT(x+c) + R&D(x+c)) / R&D(x) ]^(1/c) - 1

Where c is the average investment period of 13 years.

其中c是平均投资期13年。

Return on investment in pharma R&D is rapidly declining

新药研发的投资回报正在迅速下降

Applying this simple formula across multiple years of P&L data from EvaluatePharma, we see the following downward trend, which is fully consistent with reports published by both Deloitte and BCG:

应用这个简单的公式去拟合由EvaluatePharma汇总的多年损益数据，我们可以看到下图所示的下降趋势，这与德勤和BCG发布的报告完全一致：

Now the scariest thing about this analysis, is just how robust, consistent and rapid is the downward trend in return on investment over a period of over 20 years. But moreover, these results confirm that return on investment in pharma R&D is already below the cost of capital, and projected to hit zero within just 2 or 3 years. And this despite all efforts by the industry to fix R&D and reverse the trend.

从这个分析中看到的最可怕的事情是，20多年来，投资回报率的下降趋势非常的稳定和持续，且速度很快。而且，这些结果证明，目前制药企业的研发投资回报率已经低于资本的成本，并预计在仅仅2到3年后就将归零，尽管整个行业都在极力尝试改进研发，试图扭转这一趋势。

I mentioned earlier that this analysis is based on one assumption, the average investment period which is quite stable and well-defined, but here below we see that the results are not sensitive to this single assumption in any case. The downward trend is just as clear, as is the projected IRR of 0% by 2020:

我在前文提到，这个分析是基于一个假设，即平均投资周期是相当稳定和明确的，但下面我们看到结果对这个单一假设不敏感。下降的趋势、以及2020年的预期内部收益率降到0％都很清楚：

So what is driving this trend, and why haven’t we been able to do anything about it?

那么是什么推动了这个趋势呢，为什么我们对此还无能为力呢？

Law of Diminishing Returns

边际效益递减规律

Many different causes and drivers have been suggested to explain the steady decline in pharma R&D productivity, including rising clinical trial costs and timelines, decreasing success rates in development, a tougher regulatory environment, as well as increasing pressure from payers, providers, and increasing generic competition, however there is one fundamental issue at play that drives all these factors together: The Law of Diminishing Returns.

有许多不同的原因可以用来解释新药研发效率稳定的下降趋势，包括临床试验的成本增加和时间拖长、研发成功率的下降、监管条件更加严格、来自付款人及供应商的压力增加、更多仿制药的竞争，等等。但有一个根本性的原因将所有这些因素结合在一起：边际效益递减规律。

As each new drug improves the current standard of care, this only raises the bar for the next drug, making it more expensive, difficult and unlikely to achieve any incremental improvement, while also reducing the potential scope for improvement. Thus, the more we improve the standard of care, the more difficult and costly it becomes to improve further, so we spend more and more to get diminishing incremental benefits and added value for patients which results in diminishing return on investment, as illustrated here:

由于每一种新药都提高了当前的标准，这只会提高下一个药物进入这个市场的标准，使研发更加昂贵，难度更大，也不太可能实现任何渐进式的改善，同时还减少了未来可能的改善空间。因此，我们越是提高医疗标准，继续改善疗效就越发困难和昂贵，所以即便我们花费得越来越多，却也只能获得越来越少的疗效改善，为患者带来的收益也越少，从而导致投资回报率递减，如下所示：

But why does the analysis above suggest a linear decline that will hit 0% IRR by 2020? Shouldn’t the decline slow down and curve away so that it never reaches 0% IRR?

但为什么上面的分析显示，内部收益率将线性下降，在2020年时会达到0％？会不会下降速度逐渐放缓，呈现出曲线状，这样内部收益率永远不会达到0%？

No. 0% IRR corresponds to breaking even and getting exactly your original investment back, but as anyone who has worked in pharma will know all too well, you can easily lose all your original R&D investment as most drugs fail without making any return at all, so the minimum theoretical IRR is in fact negative 100%. There is no reason why the IRR should stop declining before it reaches 0%, or even -100%, besides the limited patience of investors.

不。0％的内部收益率就是盈亏平衡，即你能拿到的等于此前投入的，但是任何在制药公司工作的人都会很清楚，你很容易损失掉所有之前的研发投入，因为绝大多数药物的研发都会失败，没有任何回报，所以理论上，内部收益率的下限可以是负的100％。没有理由认为内部收益率应该在0％甚至-100％之前停止下降，除非投资者的有限耐心被耗尽。

To further illustrate how the Law of Diminishing Returns applies to pharma R&D, let us consider a limited set of 200 potential drug development opportunities defined by a random exponential distribution of expected costs (investments) yielding an independent random exponential distribution of expected values (returns) after an average investment period of 13 years. The expected IRR of each opportunity is given by the formula:

为了进一步说明边际效益递减规律如何作用在制药企业的研发中，我们假设有200个潜在的药物开发机会，为开发该机会而投入的期望成本（投资）由随机指数分布来定义，经过平均13年的投资期后，产生收益的期望值（回报）也由独立的随机指数分布来定义。每个机会的期望内部收益率（IRR）由以下公式给出：

IRR = [ eReturn / eCost ] ^(1/13) - 1

Now we rank and prioritize all these potential opportunities by their expected IRR over time, just as we select and prioritize drug development projects by their expected return on investment in the pharma industry, and this is what we get:

现在，我们按它们预期的内部收益率为所有这些潜在的研发机会分级并排优先级，就像在制药行业里，我们通过的预期投资回报率来选择药物开发项目并排优先级一样，这就是我们看到的结果：

Notice how the midsection of the IRR plot of prioritized opportunities follows a perfectly linear downward trend that passes right through 0% IRR, which is exactly what we have seen with our analysis of pharma R&D productivity above! The implications of this are rather striking:

请注意，这里的内部收益率曲线也是保持完美的线性下降趋势，直接穿越了0%的内部收益率，这正是我们上面对制药研发效率的分析所看到的！ 这个影响是相当惊人的：

Return on investment in Pharma R&D is declining because that is precisely how we prioritize investment opportunities over time.

制药企业研发投资回报正在下降，而这正是因为我们反复考虑投资机会的优先级所致。

In essence, drug discovery is rather like drilling for oil, where we progressively prioritize and exploit the biggest, best, cheapest and easiest opportunities with the highest expected returns first, leaving less attractive opportunities with lower returns for later. Eventually, we are left spending more value than we are possibly able to extract:

本质上，新药的发现就像石油钻探一样，我们不断地排优先级，把最大、最好、最廉价、最容易、且预期回报率最高的机会放在最前面开采，而那些吸引力较小的地方将留待以后开发。到最后，遗留下来可供开采的资源会令我们入不敷出：

Implications and projections for the pharma industry

对制药行业的启示和预测

Now given that the steady decline in return on investment in pharma R&D follows the Law of Diminishing Returns as the natural and unavoidable consequence of how we prioritize R&D investment opportunities, where does that leave the industry?

考虑到制药企业研发的投资回报率的稳定下滑遵循着边际效益递减规律，而这又是我们给研发投资机会排优先级而造成的自然而然的、却又不可避免的结果时，那么，这个行业最终又会如何呢？

We can simply extrapolate the robust linear downward trend in IRR, and then apply the same formula we used above to calculate IRR based on past performance in reverse, to predict how the industry will evolve in the future. This is what we get:

我们可以简单地把内部收益率稳定的线性下降趋势进行外推，然后应用之前我们用来计算过去内部收益率的相同公式，反过来去计算，以预测未来行业将如何演变。我们可以看到：

Wow! What we see is that the entire pharma industry is on the brink of terminal decline, and will already start to contract within the next 2 or 3 years!

喔！如上图所示，我们看到的是，整个制药行业已濒临无力扭转的下降趋势，并将在未来的2到3年内开始萎缩！

This seems incredible, but remember that this is not some arbitrary bleak forecast. It is the direct mathematical result of the Law of Diminishing Returns which we have already seen in our analysis above, and which we have been able to exactly replicate by prioritizing a limited set of random investment opportunities.

这似乎不可思议，但请记住，这并非武断地唱淡。这是边际效益递减规律的直接数学结果，我们已经看到了前面的分析过程，而且我们也已经通过生成有限投资机会的随机数、再为此排优先级来模拟这一过程。

So what is going on here? Can this really happen?

那么，随后会发生什么？这些真会发生吗？

Pharma’s broken business model

制药业破产的商业模式

The situation is illustrated nicely by this schematic here below:

下面的示意图很好地说明了这种情况：

What we have here is an industry that is entering a vicious cycle of negative growth and terminal decline as its fundamental business model has run out of steam by the Law of Diminishing Returns: Diminishing R&D productivity and return on investment leads to diminishing growth in sales. Eventually, growth turns negative and sales start to contract. Reduced sales then reduces the amount of money available to invest back into R&D, which causes sales growth to decline even further. And so on, until the industry is gone altogether.

我们所看到的是一个正在进入恶性循环中的行业，该行业正在负增长，并且无力扭转下滑趋势，因为它的基本商业模式已经被边际效益递减规律所淘汰：研发效率的降低和投资回报的减少导致销售额增长的减少。最终，增长变为负数，销售开始收缩。 销售额的减少会导致重新投入到研发中的资金的减少，导致销售进一步下滑。恶性循环不断持续，直到这个行业萎缩到消失。

This principle is further illustrated here, showing how value creation is turning negative:

下图进一步展示了这个原理，即创造的价值是如何转向负数的：

Industry life cycles and regeneration

行业的生命周期和重生

So can this happen? Will pharma really shrink out of existence, and is there anything we can do to stop it?

那么这会发生吗？制药公司是否真的有一天会萎缩到消失，我们还能做些什么来阻止其发生？

In short, yes, it can and will happen. Pharma as we know it will shrink out of existence, and no, there is nothing we can do to stop it. We know this because the steady decline in IRR is an unavoidable consequence of prioritization, and has continued despite all our efforts to slow, stop and reverse the decline to date.

简而言之，是的，这会发生、并且将要发生。我们知道制药企业将要萎缩到消失；而且，没有，我们没有办法阻止它。我们知道这一点，是因为内部收益率的稳定下滑是排优先级而造成的不可避免的结果，尽管我们一直在努力尝试减缓、阻止、和扭转这种下滑趋势，但下滑仍然会继续下去。

We should not be surprised by this. All industries and business models follow the Law of Diminishing Returns, and many industries have come and gone through history. In fact, the Pharma industry itself sprouted out from the terminal decline of the chemicals and dye industry as it was slowly commoditized. Out of the ashes grows the new.

我们不应该为此感到惊讶。所有行业和商业模式都遵循边际效益递减规律，而且许多行业业已成为历史。事实上，制药行业本身就是从化学和染料行业的致命衰退中慢慢生长起来的。在大火中涅槃才能灰烬里新生。

And therein lies the only real hope for the pharma industry — or at least the companies and hundreds of thousands of people working within it.

这是制药行业的唯一真正的希望——或者至少对于那些在该行业的公司里工作的成千上万的人来说是如此。

Just as the pharma industry evolved from the chemicals industry, and the biopharma industry has evolved from the pharma industry, the pharma and biopharma industries together will evolve into something quite different, most likely continuing the historic trend of increasing complexity towards more complex biological solutions to pressing healthcare problems, such as cell & gene therapy, tissue engineering and regenerative medicine:

正如制药行业从化学工业衍生出来，生物制药行业也已经从制药行业衍生出来，制药和生物制药行业一道将会衍生出完全不同的东西，而这正是不断增加复杂性的历史趋势。我们需要解决的那些紧迫的医疗难题倚赖于更复杂的生物医学手段，比如细胞与基因治疗、组织工程和再生医学：

But who really knows?

但谁又真正知道呢？

What is clear is that pharma (and biopharma) will not be around forever, and Darwin’s theory of evolution applies to companies and industries just as much as it applies to the species of life:

清晰的现实就是制药（和生物制药）行业不会永远存在，达尔文的进化论不仅适用于物种，也适用于公司和行业。

It is not the strongest of the species that survives, nor the most intelligent, but the one most adaptable to change.

生存下来的不是最强壮的物种，也不是最聪明的，而是最适应变化的物种。

Indeed. Adapt or die!

确实如此。要么适应，要么死亡！

作者：汤诗语

## 评论

重要提示：警惕虚假中奖信息