Bad statistics and science at MDS


The FDA sent a “warning letter”:http://www.fda.gov/cder/warn/2006/MDS_Pharma.pdf to a company called MDS Pharma late last month (posted to the agency’s website yesterday) basically saying that MDS Pharma lied with statistics. (Please note that I have not seen or review the company’s response.) Apparently, the agency found the following issues:

* Studies weren’t appropriately auditible
* The company failed to investigate outliers and other anomalous results.
* Some outliers and other anomalous results were deemed not to matter, but sufficient reasoning was not given.
* They failed to account for differences in some test-retest situations of aberrant results.
* The company used inclusion and exclusion criteria that biased their results.
* The company inappropriately documented their review of studies.
* Calibration points for their standard controls were included and excluded in a biased way and did not follow their procedures, and apparently not standard quality control procedures. (There is a Society for Quality Control for a reason.)
* Some measurement methods they used did not give repeatable results (repeatable means that the results should be very similar under very similar conditions). They took a long time to discontinue the method, but failed to inform the right people that the results coming from the method were unreliable.
* All of the above problems were widespread, over many studies of many products over several years.

And these are _nonclinical_ bioequivalence studies, not even clinical trials. (Bioequivalence studies are designed to confirm that two different formulations of the same active drug reach the sites of action in similar concentrations after they enter the body, and are “proof in the pudding” of generic drug applications.) In clinical trials any of these infractions can be very serious. According to an “article”:http://www.theglobeandmail.com/servlet/story/LAC.20060913.RMDS13/TPStory/Business in ??The Globe and Mail??,This company apparently performs bioequivalence studies for generic drug makers. This sort of behavior will have these consequences:

* You will not be able to determine if drugs are bioequivalent, if you don’t appropriately follow up anomalous responses. This endangers the regulatory submission for the generic drug maker clients.
* “We conclude that you failed to systematically investigate contamination and anomalous results” — inability to appropriately detect and handle contamination can have obvious serious effects if this is done in a clinical trial or post-marketing setup and, in a premarketing nonclinical setup, can skew results so that inappropriate or dangerous dosages are given to human subjects.
* “demonstrate that your retrospective review is capable of discriminating between valid and invalid study data,” — need I go further?

Furthermore, the company left out whole studies when communicating with the agency.

Now, what does this mean for MDS Pharma? I’ll let a securities analyst speak:

bq. UBS Securities Canada analyst Jeff Elliott said in a report that he was “concerned about the timing of a resolution of the FDA issues at MDS Pharma Services and a potential recovery of this unit.”

The markets also speak:

bq. Shares of MDS fell 64 cents or 3 per cent to $19.86 on the Toronto Stock Exchange yesterday.

Shall I issue my own “sell” recommendation (boring disclosure: I don’t own stock in pharma or life sciences companies except perhaps through mutual funds)?

My comment on this is that it doesn’t take a Ph.D. or a familiarity with standard quality control procedures to see the serious nature with these problems. I hope for the sakes of their clients that MDS can salvage some of the studies they’ve done in the last few years, and that no one has suffered due to these problems.

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One Response

  1. FDA Finds Problems in Studies by Pa. Firm…

    Federal regulators said that they have found problems with a Philadelphia firm’s review of new medicines and said that the drug companies who hired it will have to re-evaluate test results. MDS Pharma Services had been working with the Food……

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