I wonder if any efforts have been made to conduct a deep review of clinical trials to see if there are patterns of protocol design that are likely to lead to underreporting of adverse effects.
As (unfortunately) a user of a number of prescription medications, I have encountered adverse effects that were considered uncommon, yet heard about similar issues from fellow users. Of course, this is anecdata, so one can draw no conclusions, but I have a nagging suspicion that enough digging by people who truly understand statistics will find flaws, perhaps major ones.
There are a number of reasons why problems can slip through clinical trials, even with proper clinical trials design.
Some side effects are extremely rare, so rare that even with “large” clinical trials groups the problems don’t occur. Or they might occur, but at rates no greater than what the placebo group experiences. Some side effects only show up with repeated long-term use of a drug. That’s why there exists “post approval monitoring” to watch for these problems. Some side effects only show up when a drug is taken concomitantly with other drugs. Some side effects only show up when users have certain diets. Some side effects (and some efficacies) only show up for certain ethnicities and sub-populations. Some side effects only show up when patients take much larger doses than were tested in clinical trials.
Larger statistical samples would help to reduce these problems, but it’s often not as easy as you might think to recruit large numbers of people for your study. First, it is quite expensive to put a large test group together. Some diseases / conditions are quite rare, so it can be difficult to even find enough people with the condition. As the test runs through, some fraction of the participants will drop out for one reason or another. Some people will just stop taking the medication for one reason or another. How you treat these “dropouts” is not a simple question and can have a huge impact on your clinical trials conclusions. Some test measures are highly subjective and experts will disagree on how efficacious / dangerous a drug is when presented with the same exact data.
The bottom line is that drug approval is extremely complicated. Better test design and monitoring helps but it will not catch all problems. Regulators have to balance safety with benefits in the face of uncertainty.
See my other comment quoting Marcia Angell on how most of the clinical literature is rife with conflict of interest and, in general, questionable science. Some other related links:
http://en.wikipedia.org/wiki/Bruno_Latour "In the laboratory, Latour and Woolgar observed that a typical experiment produces only inconclusive data that is attributed to failure of the apparatus or experimental method, and that a large part of scientific training involves learning how to make the subjective decision of what data to keep and what data to throw out. To an untrained outsider, Latour and Woolgar argued the entire process resembles not an unbiased search for truth and accuracy but a mechanism for ignoring data that contradicts scientific orthodoxy."
"Lies, Damned Lies, and Medical Science" http://www.theatlantic.com/magazine/archive/2010/11/lies-dam... "Much of what medical researchers conclude in their studies is misleading, exaggerated, or flat-out wrong. So why are doctors -- to a striking extent -- still drawing upon misinformation in their everyday practice? Dr. John Ioannidis has spent his career challenging his peers by exposing their bad science."
"Fat, Sick, and Nearly Dead" is a funny documentary about someone who got off all his prescriptions medications by changing his diet and then helped others to do the same: http://fatsickandnearlydead.com/
This may not apply in your case, but in general, as Dr. Joel Furhman says, many prescriptions are essentially just "permission slips" to avoid lifestyle changes.
http://www.meatlessmonday.com/articles/mm-interviewwith-dr-j...
"Our healthcare system has evolved into an industry where doctors mostly provide drugs, instead of being teachers of healthy living. The medical profession is not predominantly focused on preventing disease. They are a profession that’s diagnosing and treating disease, and the reality is, the treatments hardly work and the small benefits place people at significant risk, while the underlying disease process continues to advance."
Dr. Mark Hyman and Dr. Andrew Weil are other good resources.
>> Not owning up to that uncertainty, when it is legitimate, likely will only slow scientific progress. In the controversial realm of vaccines, it will also create fodder for conspiracy theorists spreading overblown or unfounded fears among an already distrustful public.
Just when did "the realm of vaccines" become "controversial"?
Also, one thing I couldn't figure out from the article is whether Lyng and the other women who suffered after taking part in the vaccine trials actually received the vaccine, rather than a placebo. Is that information even recorded?
On conflict of interest during Gardasil's testing in India: http://www.corpwatch.org/article.php?id=14401
"JayaJan Pharmaceutical Research in India was one of the companies with which Merck had a contract to test Gardasil. Like most of the industry, Merck increasingly outsources its clinical trials to Contract Research Organizations (CROs) in areas of the world where trial subjects are plentiful, operating costs are low, and regulations lax. .. Critics point out that CROs can come with built-in problems. Conflicts of interest can arise when CROs are paid royalties only after a drug is approved rather than being paid a set fee that is independent of how safe or effective the drug turns out to be. Problems can also arise because CROs know that favorable findings mean that research into a test drug will continue, and they may also believe that results that please the hiring corporation can lead to future contracts. "[C]ompanies know that the farther the compound moves through the research cycle, the more money they can raise," Nature reported."
In general from Marcia Angell: http://www.nybooks.com/articles/archives/2009/jan/15/drug-co...
"The problems I've discussed are not limited to psychiatry, although they reach their most florid form there. Similar conflicts of interest and biases exist in virtually every field of medicine, particularly those that rely heavily on drugs or devices. It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor of The New England Journal of Medicine."
I feel like a lot of people on HN don't want to promote "vaccine denialism," but the reality is that you cannot put all vaccines, nor can you put all drugs, in the same category.
Many vaccines have done a lot of good. Many of the people who question some of the more recent vaccines are not against the standard MMR.
I don't think it's wrong to question newer pharmaceutical products, including drugs, devices and vaccines. Remember Vioxx?
Clinical trials have a lot of safeguards, but we've seen how business interests can side step these. A lot of money goes into studying new compounds. If during the animal trials, if a single monkey dies, your entire compound is often scraped and has to go back quite a but. At the human side of testing, potential issues can mean a lot of money being scrapped.
It's a bigger problem with how we develop drugs, and it's also a bigger problem with how we see science, especially the mixture of science and funding. James Corbet has a great video about the "Weaponization of Science" which is worth considering: https://www.youtube.com/watch?v=yecefLsE44U
As a general note, the validity of claims from Mercola should be taken with a large grain of salt. He publicly holds a number of frankly dangerous opinions which he bestows upon anyone who reads his website, and has made many millions of dollars from such claims and tactics.
Among other things:
Questioning whether HIV is the cause of AIDS, claiming manifestations of AIDS (including opportunistic infections and death) may be the result of "psychological stress" brought on by the belief that HIV is harmful.
Claims that microwaving food alters its chemistry, despite consensus that microwaving food does not adversely affect nutrient content compared to conventionally prepared food.
*Claiming cancer risks arise from mobile phone radiation, which is pseudoscientific.
> Like most of the industry, Merck increasingly outsources its clinical trials to Contract Research Organizations (CROs) in areas of the world where ... regulations [are] lax...
Everybody outsources to CROs, that’s what CROs are for. Yes, people do trials all over the place but by and large those investigative sites tend to be pretty good with decent controls. The study population (per FDA regulations ) has to be reasonably representative of your treatment population btw, so you couldn’t get approval for a drug in the US bas d solely on studies done in Sweden, Nigeria or India.
Some countries are pretty lax (won’t name the ones I’m thinking of because I don’t want this to come off as a slur) but the agency is going to look askance at any data you get from there and try to use for approval. But they can be OK for some early investigation (within your safety protocol) as long as you aren’t foolish enough to go ahead with a program based solely on it.
As (unfortunately) a user of a number of prescription medications, I have encountered adverse effects that were considered uncommon, yet heard about similar issues from fellow users. Of course, this is anecdata, so one can draw no conclusions, but I have a nagging suspicion that enough digging by people who truly understand statistics will find flaws, perhaps major ones.
Not likely to happen, though.