How to avoid becoming a casualty of the other Drug War — for profits at the expense of your health:

A striking feature of modern medicine is the debilitating and lethal consequences of adverse drug reactions (ADRs), which rank as one of the top 10 causes of death and illness in the developed world

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With an estimated 2 to 4 million serious injuries each year, drug therapy stands as one of the most significant perils to health resulting from human activity.

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833,076 adverse drug events reported to the U.S. Food and Drug Administration during 2014. …Although drug adverse effects are estimated to account for 100,000 to 200,000 patient deaths and 1 to 2 million hospitalizations each year

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[O]ne in every five [new drugs] eventually caused enough serious harm in patients to warrant a severe warning or withdrawal from the market

Drug companies are supposed to prove safety and efficacy in multiple clinical trials. These are then reviewed by the FDA before approval. So why do we have such a high casualty rate? Cheating.

Falsifying the Scientific Record

There is good evidence of selective outcome reporting in published reports of randomized trials…. We examined reporting practices for trials of gabapentin …We identified 20 clinical trials for which internal documents were available … of these trials, 12 were reported in publications.

A company is not going to ignore a good result. The 8 trials that went unreported were hopeless failures and swept under the rug.

For 8 of the 12 reported trials, the primary outcome defined in the published report differed from that described in the protocol. …
For a trial result to be valid, the criterion for success has to be specified ahead of time. If you can pick and choose after the fact, that is no different from shooting an arrow at the side of a barn and painting a target where it lands. So only 4 of the 20 trials actually succeeded.

For a trial to be regarded a success, there must no more than a 1 in 20 likelihood of a positive result due to chance. If you design a trial to this minimum standard, and run 20 trials, the likelihood that at least one of them will have a successful outcome by accident is 64%. So the sponsor left little to chance. If the medication actually worked as claimed, the vast majority of the 20 trials would have been successes.

But selective reporting is by no means the only method of falsifying the evidence. If the sponsor is designing a “me too” drug, it is necessary to show the drug is at least as good as the competition:

[S]ome physicians had so far forgotten their professional ethics that, again at the behest of their sponsors, they were getting the results their sponsors wanted in drug trials by hobbling the other horse in the race, the competitor’s drug, which in the trials was administered in the wrong dose by the wrong route

Or better yet:

Empirical evidence suggests that … industry-sponsored trials are more likely to compare the sponsored intervention against an inactive or straw man comparator.

If companies are going to cheat when it comes to efficacy, should we expect any better with regard to safety?

GlaxoSmithKline would not face prosecution for deliberately withholding trial data, which revealed not only that Seroxat was ineffective at treating childhood depression but also that it increased the risk of suicidal behaviour in this patient group. The decision not to prosecute followed a four and a half year investigation and was taken on the grounds that the law at the relevant time was insufficiently clear.

A depressed child is unlikely to recognize a drug is causing his or her suicidal impulses, and is in a poor position to refuse the medication. The emotional devastation wreaked upon a parent who has lost a child is horrific. Selling an ineffective drug that instead increases suicide risk among children is about as low as one could possibly go. Ethics? If a human were to behave like a corporation, he or she would be regarded as a sociopath. Unlike corporeal persons, corporate persons have no empathy, compassion, remorse nor fear of punishment. Pharmas will strive to hide any risk and claim any benefit that they can get away with.

What about whistleblowers?
Meanwhile sponsoring companies threatened the researchers to prevent them from publishing unfavorable results.

They had signed non-disclosure agreements. To complete the picture:
Metaanalysis is a rigorous technique whereby all the literature concerning a particular drug could … be identified, and … the efficacy of the drug in all comparable high quality trials, could be worked out… it was found that companies were paying physician scientists to publish the same results of the same trials in different journals, under different authors’ names, with no crossreferencing.
Since they were also paying scientists to publish only the positive results, and bury the negative ones, this systematic obfuscation had the effect of creating artificial scientific support for a drug, both before regulatory agencies, and, of course, to impress the prescribing physician.

And afterward:

Post-Marketing Surveillance

As for post-market surveillance — “the single most important function…for protecting the public against the dangers of harmful drugs” — it is put largely in the hands of the manufacturers

What do drug companies do with this awesome responsibility? Fox, meet henhouse...

Damage Control After Approval

Damage control for them means damage to us. Their tactics are:

• Once serious adverse effects become known, minimize the risk.
• Place convenient, seemingly impartial and well-referenced summaries in places doctors will look
• Persuade patients to take, and keep taking the offending drug in spite of risks and warning signs.

Their means toward this end is to employ physician “experts” to write convenient, comprehensive, well-referenced reviews of the medication. Convenient for a busy doctor because everything s/he needs to know is all in one place instead of having to chase through the literature to find different details. These seemingly respectable pieces show up in seemingly respectable places, like Mayo Clinic and Medscape.

As an example, let’s try Google Scholar to search for “adverse effects” and Fosamax. The first result is an impressive looking article from Mayo clinic. Google thinks this is the most relevant result because it is the most frequently visited. Clicking on it, we get this full text for free instead of an extortionate fee. Now heading to Subtrochanteric Femoral [i.e.,hip] Fractures:

Although these bisphosphonate-associated fractures are uncommon, several case reports have described some of their typical clinical features. .... Recently, the association between such fractures and bisphosphonates has been questioned, and these fractures were suggested to be merely an uncommon subtype of osteoporotic femur fracture

Oh OK, uncommon. Just a few case reports, maybe not drug related at all. Nothing to see here (to be continued).

Uncommon? Underreported:

It is estimated that as few as 5% of all adverse drug reactions are reported to appropriate agencies. Underreporting is likely related to ... failure to recognize adverse drug reactions when they occur. Children are particularly vulnerable.

Underreported because physicians think drugs are safe:

Factors associated with under-reporting [drug adverse events] were ...indifference (the one case that an individual doctor might see could not contribute to medical knowledge) and insecurity (it is nearly impossible to determine whether or not a drug is responsible for a particular adverse reaction) in 67%; and complacency (only safe drugs are allowed on the market) in 47% of studies.

Damage Prevention

We have seen that the record is thick with false information. If you are so inclined, there is a wealth of information to be found at Google Scholar. Be properly skeptical of the vast number of studies praising a drug’s benefits and minimizing its drawbacks. If you are looking for adverse effects there, best to search on the drug class, for example, bisphosphonates for Fosamax. If you don’t know what effect you are looking for, use “adverse effects”. Then search individually on a specific adverse effect. Exactly how to search in this manner is narrated in the Statin research below.

Always Check the FDA label — you can get this via a web search for “FDA label” and the drug name. Pay special attention to listings of adverse effects, drug interactions, whether to take with or without food, and the effect of mineral supplements.

This is not enough though, because information regarding important adverse effects is likely to have been concealed by the manufacturer. At the other extreme, there are alarmists out there with websites long on outrage and short on facts. This will not do either.

Useful sites:

askapatient.com— Compiles patients’ ratings of medications on a scale of 1-5 and presents their individual commentaries. Compares ratings of different medications in the same class. Provides a summary of adverse events reported to FDA. Excellent site. Only caution: in some cases the average rating is derived from a small number of individuals. (Originally suggested by SSK in the comments)

patientsville.com — Lists side effects by frequency of patient reports, by individual medication. It also displays individual patient reports. The downsides: it is extremely slow, and the user interface is uneven. It takes scrolling down to get side effects by frequency. Note that this does not tell you how severe the side effect is. In the case of “femur fracture” this is self-evident, but in the case of myalgia it is not. It looks like they are using reports submitted to the FDA as well as reports submitted to the site.

Attorney websites are a good source of information. Attorneys will not hide any problems, nor will they make alarmist claims that would not be actionable:

• Drugwatch — They have a list of drugs and adverse effects. Not comprehensive — none of these attorney sites are. Some additional information showed up via google site search.
• Lawyers and Settlements — They’ve got lists of lawsuits, past and present. They set forth the allegations in the suit, and the result if the suit has been decided.
• American Injury Attorney Group > Lawsuits > Bad Drugs — A list of drug lawsuits. They tell you what the drugs did to cause the suit.

Consumer Reports has a list of 10 drugs to avoid.

Here is a database intended for doctors that lets you search for drugs indexed by adverse reaction. From their front page:

The sole fact that the patient knows that ADRs [adverse Drug Reactions] can occur is enough to discourage the patient let alone if the individual should actually experience such a reaction during therapy

The implication being the doctor should not warn patients of possible adverse effects, and should minimize them if reported. We already know that some physicians believe only safe drugs are allowed on the market. This is bad news. For some medications the onset of certain side effects is a dire event. In such cases the medication should be stopped immediately lest really serious damage ensue. Two examples are:

• Fluoroquinolones (Cipro, Levaquin, etc.) — tendinitis or neurological symptoms
• Dopamine Agonists (medications for Parkinson’s and Restless Leg Syndrome) — lightheadedness or impulse control disorder (established users must taper slowly)

Impulse control disorder? That refers to compulsive gambling, sexuality, or eating. Some patients who had previously been responsible citizens have lost everything due to dopamine agonist induced compulsive gambling. Many patients did not realize the drug was causing it.

​So when taking a new medication, be on the alert for any adverse effect. It may occur immediately, or be delayed for quite some time. If you experience some new symptom, get to work and search askapatient, patientsville, Google Scholar and the web to see if the medication may be the cause, and the possible outcomes. In any event, ask your doctor for a different medication. If you can quit the medication safely, do so.

Just Say No to Bad Drugs

BISPHOSPHONATES

(Fosamax, Reclast, Zometa, Actonel, Boniva, Aredia)

[S]ubtrochanteric and diaphyseal fractures occurred at a rate of 13 per 10,000 patient-years in untreated women and 31 per 10,000 patient-years in women receiving alendronate [Fosamax]

The subtrochanteric is the top of the femur near where it enters the hip socket. If it breaks, this is a hip fracture. The diaphyseal is also the femur but lower down. So according to this study, Fosamax more than doubles hip fracture risk. The authors go on to speculate that maybe the increased risk is due to osteoporosis in Fosamax patients, Hence the comment in the whitewash posted at Mayo Clinic:

these fractures were suggested to be merely an uncommon subtype of osteoporotic femur fracture
Fosamax was supposed to solve that problem. Yet the FDA label says:

FOSAMAX increases bone mass and reduces the incidence of fractures, including those of the hip and spine
It does increase bone mass but that is not the same as bone strength. How did this happen? From that same label:

In the Three-Year Study ...fractures of the hip occurred in 22 (2.2%) of 1005 patients on placebo and 11 (1.1%) of 1022 patients on FOSAMAX, p=0.047.
The cutoff is p