Study Design Flaws Led to Conclusion That Statins Lengthen Cancer Patients’ Lives, Researchers Say

Study Design Flaws Led to Conclusion That Statins Lengthen Cancer Patients’ Lives, Researchers Say

Starting cholesterol-lowering statin therapy within six months of a cancer diagnosis does not improve patients’ survival at three years, according to a study that found scientific bias in previous research.

The study, “Examining Bias in Studies of Statin Treatment and Survival in Patients With Cancer,” was published in JAMA oncology. It dealt with the findings of previous observational research — studies that are more prone to bias because they do not include control groups.

A number of previous studies have reported that cancer patients who use statins do significantly better than those who don’t. In fact, research has shown that 18-44 percent of prostate, breast, and colorectal cancer patients who are on statins survive longer than those who aren’t on them.

Statins also lengthen the lives of people without cancer, studies have shown. This has intrigued the scientific community and ignited further research in the area.

Researchers decided to look at whether two kinds of scientific bias could have played a role in studies that suggested statins increased cancer patients’ survival.

Actually, three types of bias could have creeped in, they said.

One is bias from confounding variables. This could have occurred if the results were not properly adjusted for factors associated with the start and completion of statin therapy.

Another possibility is selection bias. Those conducting the studies could have included many people who were using statins at the time of their cancer diagnosis.

The third possibility is immortal-time bias. It could have surfaced when researchers classified study participants who died before receiving statins as non-statin users. This bias would make a connection between statins and cancer survival appear stronger than it actually is.

While confounding variables bias is inherent in an observational study, the other two kinds would have come from flaws in the study design.

The researchers decided to investigate whether selection bias and immortal-time bias could explain the correlation between statins and cancer patient survival.

They looked at the records of 17, 372 cancer patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The registry covers people with colorectal, breast, prostate, or bladder cancer.

The team first analyzed the data in a way that would reduce selection bias. Then they analyzed it in a way that would reduce immortal-time bias. Finally, they analyzed it in a way that would reduce both selection and immortal-time bias.

They discovered that when selection and immortal-time bias is eliminated from the study design, there is no difference in cancer survival between statin users and non-users.

The bottom line, the team said, was that bias can lead to the wrong conclusions in observational studies.

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One comment

  1. Stephen B. Strum, MD, FACP says:

    I am flooded with papers that are departing from actual patient chart in-depth reviews & are relying on “data” such as insurance billing, based on diagnostic codes. In addition to the morass of the above papers, we also have papers that are not being “vetted” insofar as selection bias as pointed out in the important publication by Emilsson et al (Emilsson L, Garcia-Albeniz X, Logan RW, et al: Examining Bias in Studies of Statin Treatment and Survival in Patients With Cancer. JAMA Oncol, 2017.) Medical decisions of importance are often based on publications that turn out not to have confirmation in the context of patient context (i.e., the clinical world). This is a serious issue, not only so far as misleading information, but often in terms of adverse side-effects generated by drugs that in fact are ineffective, and by healthcare costs & the misdirection of clinicians. In my focused world of prostate cancer I noted a flurry of papers on dramatic prolonging of PSA doubling time (PSADT) from the use of POM Wonderful’s pomegranate product that was used by millions (Pantuck AJ, Leppert JT, Zomorodian N, et al: Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res 12:4018-26, 2006). Yet 9 years later that initial report was refuted by the same original authors (Pantuck AJ, Pettaway CA, Dreicer R, et al: A randomized, double-blind, placebo-controlled study of the effects of pomegranate extract on rising PSA levels in men following primary therapy for prostate cancer. Prostate Cancer Prostatic Dis 18:242-8, 2015). How many millions of dollars were spent on that supplement & how many men might have been treated with something that was actually effective?

    In the world of statin therapy I am perplexed by the studies that continue to use baseline & follow-up standard lipid panels instead of the valuable information provided by the NMR lipoprofile. I see patients with elevated total cholesterol with normal NMR lipoprofiles and those with normal standard panels with abnormal NMR lipoprofiles. We live in a world of informational “glut” but also in a world where information itself is not vetted. I have rejected papers that were grossly unfit for publication only to see the same paper, with no significant editing, published a few months later. Pathology diagnoses of cancer are not read by experts in the pathology of that particular tissue; imaging exams are read by general radiologists and not experts in PET/CT or in multi-parametric MRI (mp-MRI). What we have is the Trumpian medical counterpart of “fake news”.

    Even reputable centers publishing on advances in the imaging of cancer are not reporting on head-to-head studies comparing that new advance with the so-called gold standard. So how do I as a MedOnc tell a patient that 68Ga-PSMA PET/CT is superior to NaF PET/CT in the diagnosis & assessment of bone metastases when no such head-to-head studies have been published? Simple. I can’t. The Emilsson et al paper is a major red flag warning us of the slew of similarly designed papers. But these findings are relatively ignored, and progress that can be made is diluted with medical jetsam & flotsam.

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