Scientists from Australia and America called for open access to prostate cancer-specific clinical data from the two major and highly influential European trials conducted on prostate cancer screening. This was done to settle controversies around the test policies in an article published in The British Medical Journal (BMJ) on May 25th, 2016.
The United States Preventive Services Task force (USPSTF) recommends against screening men aged 55 to 69 for prostate specific antigen, marking it with a D grade which represents moderate to high certainty that the service would not provide any net benefit or harm that will outweigh the good. An urology association in Australia and New Zealand however recommends testing for the same aged group of men.
When seeing these varying recommendations, along with facts like 1) 2 – 3 % of the men die from painful prostate cancer at an average age of 80, 2) the incidence of the disease is nearly 25 % within the generally accepted range of prostate specific antigen, 3) overdiagnosis and overtreatment can result in little benefits and exponential side effects like impotence and urinary incontinence; in these cases the physicians are bound to turn to other evidences.
Three major trials come into play, the European Randomized Study of Screening for Prostate Cancer (ERSPC), the Gothenburg trial and the US Prostate, Lung, Colorectal and Ovarian (PLCO) trial. The United States PLCO trial has already made its data public and has found no benefit for the prostate specific antigen. The other two European trials however have not disclosed their data.
The European trials have given their recommendations in favor of the prostate testing with significant association between relative risk reduction in death from prostate cancer and the prostate specific antigen screening.
The authors of the article however want the data from these two trials which influence public health policy recommendations for prostate cancer to a large degree and also influence many men around the world to have regular screenings.
Ian Haines and his colleagues raise several points on why they need that particular set of data like the fact that it has not been answered whether the improved outcomes associated with the screening are a result of differential treatment or assessment criteria? or are they, in fact, a direct result of the screening effort itself?
Both European trials and respective institutes are funded by tax payers and philanthropic efforts, which dictates the public sharing of the data with relevant personnel, institutes, and especially funders of the trials. World Health Organization (WHO) and European Medical Agency (EMA) have policies in place which dictate that data recipients should have complete access and freedom to reanalyze the said data.
Carlsson and the team for the Gothenburg trial have maintained that the data from the trial is ‘not available for outside investigators’.
On the other hand ERSPC trial team of scientists has stated that the data is still undergoing analysis and it would only be available when their analysis would be complete.
Evaluation efforts done independently have raised questions as to why some key issues were not directly discussed and explored in the ERSPC trial like-
- Extent of the contaminated evidence from previous screenings conducted in the seven countries from Europe.
- Was use of androgen deprivation monotherapy for the control group associated with increased mortality? This could potentially affect the answer to the question, did the screening efforts reduce deaths?
- Was the data pooling between the seven countries accurate or not when five of the seven studies did not even find any benefit for the screening?
- Whether the research groups claims are valid and why the reduction was not significant in a wider age group than 55-69?
- Whether there was an awareness bias in the groups?
- Extent of harm that screening and treating men for early stage prostate cancer can impart.
Harlan Krumholz, MD, and Eric Peterson, MD, MPH, have previously highlighted how open access to clinical trial data, when reanalyzed, can help and change already perceived public health policies. They have observed that since 1966 only 37 reports meet the criteria for the reanalysis of a randomized control trial and 84 % of them have overlapping authors which means that the reanalysis attempted were not independent.
Krumholz stresses that reanalysis of clinical data is significant as discordance between reported data in clinicaltrial.gov and the data published in the journal articles is present on a large scale. A random sample of phase three and four trials showed that the primary end points (outcomes) of 15 % of the trials were different in the journals and at the site.
The researchers called open science and replication ‘a standard for all trials’ and especially for those with high potential to influence practice and policy.
Cancer.org reports that besides skin cancer, prostate cancer is the most common cancer in United States’ men , with every 1 in 7 men receiving a diagnosis during his lifetime.
The American Cancer Society estimates also suggest that 180,890 cases of prostate cancer and 26,120 deaths due to it will occur in the country in this year.