Swine Flu, Vaccines, and Mathematical Models

The recent swine flu outbreak in Mexico reminds me that, although lately I’ve been working on other things, I should also continue my work in health policy research and related areas.

Here we consider the problem:  in a flu pandemic, what strategies can we use to conserve scarce vaccine?

Let’s assume, for example, that during the first 3 months of a flu pandemic, a country has 1 million doses of flu vaccine.  How can this quantity, which is not sufficient to immunize the entire at-risk population, be used as effectively as possible?

First we need to decide what “as effectively as possible” means.  Is the objective to minimize total mortality, to minimize mortality and morbidity, to maximize what are called QALY’s (quality-adjusted years of life), or to reduce negative economic impact?  All of these are defensible criteria.  This requires some careful analytical modeling and work.

As just one example related to this, should scarce vaccines be direct more towards children, young adults, or older adults?  Older adults are a likely target, as they have the highest mortality rates in a flu pandemic.  However they are, unfortunately, least likely to exhibit a positive immune response to flu vaccines.

Conversely, children respond well to the vaccines; and by potentially saving a child’s life, one theoretically gains  many years of productive life. Further, while this may require further epidemiological study, children, who attend school along with dozens or hundreds of other children, are probably disproportionately both at risk for flu and involved in transmission once they catch it.   However school-age children also tend to have fewer complications and lower mortality rates with flu.

In the end, an optimal allocation of flu vaccine may require a fairly complex analysis and/or computer simulation.  Various parameters that feed these analyses would need to be quantified beforehand.  For this we would have two choices:  (1) either estimate the parameters based on a combination of guesswork and literature review, or (2) to conduct small experimental studies aimed to supply more realistic values.

The choice between (1) and (2) could itself be made by performing mathematical sensitivity analyses within the simulation models; highly sensitive parameters — those for which small differences have a large effect on results — would be worth investing more money to quanity precisely.

In general, it should be noted that everything discussed here — simulations, literature reviews, mathematical analyses, etc. — are extremely inexpensive compared to the costs of large-scale population immunizations.  Half a million dollars, say, buys an immense amount of mathematical research.  And it could easily save tens or even hundreds of millions of dollars by preventing disease or streamlining immunization efforts.

Predicting Individual Response to Vaccine

Another productive area of mathematical modeling here would be to try to predict individual  response to vaccines.  For a given flu vaccine, only a certain proportion of people develop the intended antibodies.  For a particular population and vaccine, for example, this rate may be only 70%.  It would be worthwhile to know in advance whether a given person is among the 70% that respond to a vaccine or the 30% that do not.  If someone won’t probably won’t respond, spare the vaccine dose and give it to someone who will.

Such analyses can be performed using routine predictive statistical methods, like logistic regression, or perhaps more modern techniques.  Possible predictor variables might include:  subject age, sex, immunization history, flu history, ethnicity, overall health, weight.

Other predictive variables might be measured via blood tests or even DNA testing.  The choice concerning how heroically to collect predictive variables would depend on factors unique to the pandemic, such as the virulence of the strain, and the amount of existing vaccine.  In theory, if a flu strain is dangerous enough, and if vaccine is scarce enough, literally every available dose must be directed to someone it can potentially benefit.  In that case even as expensive (currently) a procedure as micro-array DNA screening could be utilized.

Other benefits from mathematical modeling and prediction in a pandemic might come by analyzing cross-reactivity of previously-developed vaccines for the current flu strain.  In the past vaccines have been developed for perhaps dozens of flu strains.  In theory, each of these vaccines is unique.  The usual assumption is that a vaccine for one flu strain offers little or no protection for a new strain.
However, that is not always the case.

The only way to be sure would be to test old vaccines against the new flu strain.  In theory, this could be done using human subjects in only a few days, at the outset of a pandemic.  All that is required is to administer an old flu vaccine to a subject, wait a few days, and then see if their blood contains antibodies effective against the new strain.

Perhaps this is a long-shot, but we might get lucky, and would lose nothing by trying.

An even more elaborate strategy would involve trying to predict cross-reactivity of previous flu vaccines to the new strain in a particular patient.  That is, by considering demographic, biological, or genetic variables of a given subject, we might identify those will exhibit favorable crossreactivity.

In addition, we could probably make some good guesses about crossreactivity simply by comparing the genetic composition of the new strain to previous ones, and applying mathematical or artificial intelligence models.

More broadly, there’s a lot more we can do at the behavioral level to prevent or limit a flu pandemic.  Public information aimed at teaching people how to prevent spread of flu is effective and cost-effective.  The pharmaceutical company GSK, for example,  has produced some excellent web-based presentations that teach people about flu prevention.  People need to learn, for example how to wash their hands correctly (30 seconds; warm water; wash both sides and between fingers).

Personally, I would like to see studies done on the potential preventive effects of wearing surgical masks on airplanes or subways.  Or perhaps, in the case of airlines, does anybody know what’s going on with the air recirculation system?  Is it filtered, and, if so, can the filters trap virus-bearing dust particles?  Airlines might be reluctant to address this issue.  Pictures of mask-wearing passengers isn’t exactly good advertising.  But on the other hand, people now are already avoiding air travel because of flu fears.  If the airlines could show that masks significantly reduce risk of contagion it might actually be good for them.

Nothing to Fear but Fear Itself – 2009

Nothing to Fear but Fear Itself – 2009

The famous words, “The only thing we have to fear is fear itself” come from the first inaugural address of Franklin D. Roosevelt (March 4, 1933). These comments, of course, were made in the midst of the Great Depression. The parallels between those times and the current economic crisis are worth considering.

Roosevelt’s address contained some other remarks applicable to our times:

“This is preeminently the time to speak the truth, the whole truth, frankly and boldly. Nor need we shrink from honestly facing conditions in our country today. This great Nation will endure as it has endured, will revive and will prosper. So, first of all, let me assert my firm belief that the only thing we have to fear is fear itself — nameless, unreasoning, unjustified terror which paralyzes needed efforts to convert retreat into advance.”

and also:

“Yet our distress comes from no failure of substance. We are stricken by no plague of locusts. Compared with the perils which our forefathers conquered because they believed and were not afraid, we have still much to be thankful for. Nature still offers her bounty and human efforts have multiplied it. Plenty is at our doorstep, but a generous use of it languishes in the very sight of the supply. Primarily this is because the rulers of the exchange of mankind’s goods have failed, through their own stubbornness and their own incompetence, have admitted their failure, and abdicated. Practices of the unscrupulous money changers stand indicted in the court of public opinion.”

and, further:

“Happiness lies not in the mere possession of money; it lies in the joy of achievement, in the thrill of creative effort. The joy and moral stimulation of work no longer must be forgotten in the mad chase of evanescent profits. These dark days will be worth all they cost us if they teach us that our true destiny is not to be ministered unto but to minister to ourselves and to our fellow men.“

Unfortunately (in my opinion), Roosevelt was correct in his diagnosis but wrong in his response. He leapt to the conclusion that the correct solution was to supply the federal government with massive new powers. It was correct to conclude that the solution was to be found in new commitment to service of others, but arguably incorrect to assume that the federal government must be the primary agent of this. We have paid the price of that decision ever since. Indeed, some suggest that the current economic problems are partly the result of ill-advised government policies and regulations in the 1990’s. Thus, Roosevelt also said in the same speech:

“But in the event that the Congress shall fail to take one of these two courses, and in the event that the national emergency is still critical, I shall not evade the clear course of duty that will then confront me. I shall ask the Congress for the one remaining instrument to meet the crisis — broad Executive power to wage a war against the emergency, as great as the power that would be given to me if we were in fact invaded by a foreign foe.”

However this is no place to criticize the policies of FDR. The goal, rather, is to make two points about the current situation.

The first is that things now are not necessarily as bad as people (especially the media and governments) are making it out to be. What really counts in life are love, happiness, kindness, friendship, respect, virtue, education, and, above these all, religion and spirituality. Not only are these things money can’t buy, there is general agreement that unnecessary concern for money interferes with them.

In reality, at least those of us in the United States and Western Europe, things right now are, comparatively speaking — not that bad. Perhaps life is not (or superficially does not appear) quite as nice as 15 years ago. But, overall, it’s still better than it was 100, and probably even 50 years ago. (Recall that 50 years ago we didn’t have computers, the internet, mobile phones, compact discs, or color televisions.)

The most important of today’s problems have nothing to do with the recent economic crisis. They concern things like insufficient planning, inept government, easily preventable chronic disease, and loss of moral direction. In short, we are today experiencing a “values crisis” which far exceeds in importance any kind of economic crisis.

Further, one must seriously question whether the crisis is being exaggerated for the express purpose of producing fear in the citizenry. Fear, and its companions, anxiety and anger, have the effect of reducing the ability of the mind to focus on and solve problems. Were it not for incessant fear in modern society — a fear actively fed by popular media — perhaps we would wake up and realize how good we actually have it.

Yes, the current economic “bailout” is equivalent to placing each US citizen two or three thousand dollars in debt. So what? Before that happened I had to wake up each morning, go to work, and earn a living. It can be difficult, but it can be rewarding, too. And today nothing changes. I still do the same work, and in most outward ways my life is the same, yet somehow there’s this ominous word “crisis” floating about.

It is a blessing to be alive. It is a blessing to be in the midst of other people. The only problem is our own inability to see what great, miraculous things these are!

But this post isn’t a simple morality sermon. Yes, I would indeed exhort all to discover the immense potential of love and joy in their lives. But I am more really more concerned here with drawing attention to what prevents this, which is fear.

The System creates fear. The System wants fear. That is the problem we have to face and overcome.

But what is the System? We know it exists. We suspect that in involves interacting levels of government, economic institutions, and the media. But we can’t define it exactly. Its very ambiguity, in fact, is one of its most problematic features.

But fear is its greatest weapon, because once the mind is occupied with fear, the two things the System most wants to prevent — namely love and reason — are crowded out.

At least we can say this much with some confidence: whatever produces fear, especially in a widespread and systematic fashion, is likely a direct manifestation of the System. Knowing this we may remain alert, prepared to defend ourselves, and able to avoid getting drawn into fear. We know the face of the enemy.

However it is too simplistic to merely to see an external System as the cause of all our problems.

While, again, the details are not clear, it is nevertheless a consistent empirical observation that the System is somehow connected with our own internal states.  To some extent the System is a projection or external manifestation of our own personal disorder.  Thus our primary weapon against the System consists in self-improvement, growing in virtue, and purifying the ego.

Here we have alluded to two related but distinct issues.  There is fear, but there is also failure to appreciate the good things in life.  It is not only that fear makes us unable to see the good things.  To a certain degree the reverse is also true:  by failing to remember and see the good things, we leave ourselves open to fear.

Thus, fear and failure to appreciate the important things interact:  fear reduces mental clarity, and lack of mental clarity makes us unable to consciously direct our attention to positive things and away from fear.

However living in a community of other human beings works to our advantage here.  We should use every opportunity to build up others, to encourage them, and to direct their attention to positive things.

Libertarian Tea Parties

Libertarian Tea Parties

On April 15, 2009 (the date that US tax returns are due) dozens of libertarian groups around the country will stage protests, called Tea Parties (named after the famous Boston Tea Party of 1773). The purpose is to “voice opposition to the out-of-control spending and taxation started by the Bush administration and carried on by Obama.”

This sort of grassroots activity is exactly what’s needed these days. The organizers are to be commended. It’s only in the United States that something like this would happen. More Americans need to mobilize, organize, demonstrate, and express themselves in this way, because: (1) it’s the right thing to do; (2) it’s effective; (3) it keeps the flame of Liberty alight; and (4) it serves as an example for the rest of the world.

My one suggestion is to not personalize this by blaming President Obama. The problem isn’t the president, it’s the economic-political System in the US. The System *wants* people to personalize things, and to express hostility. That insures that accusations merely flow back and forth, and nothing constructive gets accomplished.

Flat Income Tax

And while we’re at it, let’s not forget the idea of income tax reform, and, in particular, the idea of a flat tax. To adopt a flat tax would go a long way towards getting the US economy back on track. The flat tax is a winning proposition for everybody. It can lower the marginal tax rate across the board, yet generate more tax revenue. This happens because:

1. People and companies don’t need to waste so much time (days, weeks) merely figuring out their taxes and doing the necessary accounting on an ongoing basis;
2. Compliance will be improve because everybody will view the system as fair and positive;
3. Companies and the rich will spend less time finding clever ways to avoid their taxes and more time producing what they’re in business to produce.
4. In an economy stimulated by the flat income tax there would be more business activity, more income, and more total income tax paid, even though the marginal rate is reduced.

Advice for President Obama: Let America Reach Out to Developing Countries

Advice for President Obama:  Let America Reach Out to Developing Countries

Yesterday I saw a photo of Obama’s face.  His expression looked concerned.  It looked like a man who is truly idealistic and trying hard, but finding all his best efforts frustrated.

That’s probably the case.  Obama seems like a genuine idealist at heart.  Unfortunately, he’s also, in a de facto sense, a “company man.”  The fact is that he still fronts the status quo political system, and the economic-corporate structures that control that system.

Obama received much more in corporate campaign contributions than his Republican rival, John McCain (that’s a little ironic, given that the Democrats are always complaining about how it’s the Republicans that are controlled by big business.)

We also need to remember the debates, which are controlled by corporations along with the Democrat and Republic parties.  Third parties — and the new ideas that they might present — are excluded.

He can’t easily ignore corporate special interests now; he’s beholden to them.

But I don’t want to rant on that.  These facts are true, but it also seems true that Obama is an idealist.  In his mind, perhaps, he ‘used’ the system to get elected, hoping that once in power he could accomplish good.

So, assuming that’s the case, and that Obama truly wants to do what’s good for America, here’s a suggestion.

The first priority for Americans is a change of heart.  We need to understand (1) what great gifts we’ve been given, and (2) how great an opportunity, honor, and responsibility we have to share these with the rest of the world.

We were given a blessed land.  A land of plenty.  We were given security.  Most of all, we’ve been given a country founded from its beginning on principles.  We are indeed a shining city on the hill — if only we could see this.  The hopes of countless generations came to fruition when a true democracy, a “government of the people, by the people, for the people” was founded on our shores.  The rest of the world wants to learn from us, to follow our example.  If only we would give them good reason to!

What we must do now is to reach out our hand to help other countries, especially the poor and underdeveloped countries.  We have to stop being so selfish and self-centered.  “In losing your life you will find it.”  That is as true at the collective level as at the individual one.

There’s no need for me to pursue this topic at length here.  It’s only common sense.  But for some reason people seem to think common sense no longer applies.  That’s a mistaken assumption.   We can and must do what is right.  Some specific suggestions along these lines are found in previous blog entries, The American Library at Leuven and Forgotten Wisdom: Eisenhower’s Vision of America.

Rlated posts:

America’s Malaise:  What’s the Real Problem?

The Commission on Presidential Debates:  A National Scandal