PRP: Platelet Rich Plasma, or just Profit Rich Placebo?

I am continuing in the same vein as my previous blog about BMP (yet another TLA: Three Letter Abbreviation).

Platelet Rich Plasma is another example of a product that sounds so good, it must work. You would think that if doctors were scientific, they would not be influenced by the name of a product, but you only have to talk to anyone employed in marketing for about 5 minutes before you understand that the name of a product can be as important as its performance. Results are important of course, but so is the presentation (name, packaging, advertising, etc.), and we know that doctors are definitely influenced by advertising (another topic, but click here for a good starting point).

PRP has been around for a while. The product is actually fairly simple: take some blood from the patient, and spin it down until you have the plasma with all the platelets in it, and inject it into the diseased tissue. Platelets help blood to clot, but they also contain other factors (that have equally impressive names, like PDGF: Platelet Derived Growth Factor) that have been shown in laboratory settings to do all sorts of amazing things (don’t get me started on the mismatch between lab research and real life). PRP is being used by doctors to inject around sore tendons, bones that aren’t healing, and anywhere that hurts. Tiger Woods had it, as have many other high profile sports stars. Claims from the internet are often positive, like this NY Times article which includes quotes from academic surgeons such as “PRP has the potential to revolutionize not just sports medicine but all of orthopedics” and “I call it a growth factor cocktail”.  To their credit, they published an article a year later that was not as effusive.

But does PRP really work? Where is the science that can reveal the truth behind the hype?

You need to look at randomised controlled trials (RCTs) for something like this, and particularly ones that compare it to a placebo. Like with BMPs, the lack of a placebo can be confusing and lead to incorrect conclusions. So let me review the evidence.

For injections around the Achilles’ tendon, two RCTs (click here and here) compared it to placebo injections and found no benefit.

Similarly, two RCTs (click here and here) tested it against placebos in anterior cruciate ligament reconstructions and found no benefit.

In the shoulder after rotator cuff surgery it also doesn’t help in the long term (click here and here) and the topic was reviewed in a stem cell journal. These studies are illustrative of the prevailing bias. The first article showed a benefit at 3 months that did not extend to 6, 2 or 24 months, and the post hoc subgroup analysis that showed a benefit in one particular group of patients should be discarded. You can always find a subgroup in which your treatment worked, but if you didn't design your study to test that hypothesis, then scientifically, you can't go there. Even the second study, that showed no benefit in small and moderate tears seemed to want it to work. Instead of concluding that it didn’t work, they said: “it is possible that [PRP] may be beneficial for large and massive rotator cuff tears [which weren't even part of the study, so why would they believe that?]. Also, given the heterogeneity of [PRP] preparation products available on the market, it is possible that other preparations may be more effective”.

The only surgical study I could find on the topics above that showed PRP to be helpful was when it was compared to corticosteroid injection (link). That tells me that steroid injections might be bad for you, and I back the placebo studies over alternative treatment studies every time.

For dentistry, there are a lot of studies, with most of them being for bony defects (cavities in the bones around the teeth after (say) dental extraction. I searched all of the articles in the National Library of Medicine (using Medline) focussing on randomised trials of platelet rich plasma and found 66 studies, mainly dental. Rather than read every study and weigh them up (I am not a dentist) I have just taken a direct quote from the results or conclusion from every study that compares PRP to something else for bony defects, and listed them below to give you a flavour. They are roughly in chronological order, and are printed small so skip over them if you like.

“the use of PRP has failed to improve the results”

“A progressive extinguishment of the PRP effect is recorded”

“results also suggested that PRP added no clinical benefit”

“using PRP with BG has no additional benefit”

“the use of PRP failed to enhance the results”

“The use of PRP to support bone regeneration cannot be recommended”

“PRP had no effect on hard tissue fill or gain in new hard tissue formation”

“No statistically significant differences in any of the investigated parameters were observed”

“failed to increase the osteoblastic activity”

“no positive effect of PRP on bone density”

“PRP did not improve the results”

“implies a limited role of autologous PRP as a regenerative material”

“PRP is not a determining factor for implant survival”

“the use of PRP failed to improve the results obtained with ABBM alone”

“There were insufficient data to support the use of PRP to promote bone healing or to enhance the quality of life of patients”

“No appreciable clinical effect could be observed when using PRP”

“No significant differences in the postoperative (pain, swelling, trismus and infectious events) were observed”

“The addition of PRP to bone graft appeared to enhance bone regeneration considerably”

“Combination of PRP and beta-TCP led to a significantly more favorable clinical and radiographic improvement”

“PRP gel has a beneficial effect in enhancing socket healing”

“PRP may be an alternative treatment”

“No statistical differences were observed on the seventh day and sixth month of investigation, yet there were higher means of radiographic bone density in sockets treated with PRP”,

“[PRP] significantly reduces postoperative bone resorption”

It should be noted that the more recent studies tended to be favourable, possibly reflecting improved PRP quality over time, but the treatment differences were small, and study numbers were small in all studies. But the reigning bias in favour of PRP in dentistry is summarized by RE Marx 2004 in his 2004 article, written before any of the positive studies (above) were published. He summarises: “The value of PRP is its proven effectiveness”

A lot of the RCTs have looked at wound healing, where it doesn’t fare much better. While it might help with some types of foot ulcer, and acute traumatic wounds, it failed to make a difference in vein harvesting wounds, hernia wounds, tonsillectomy wounds or toenail surgery.

But why am I reviewing it? Somebody has already reviewed the use of PRP in orthopaedic surgery and published it this year in the Journal of Bone and Joint Surgery (American volume) here. They conclude: “There is uncertainty about the evidence to support the increasing clinical use of platelet-rich plasma and autologous blood concentrates as a treatment modality for orthopaedic bone and soft-tissue injuries.”

Finally, you are probably saying that if Tiger Woods wants to have it injected, what’s the harm? And this is where I go back to my recurring theme of how doctors (and the public) don’t just overestimate the benefits (as described above), but they also underestimate the harms. One injection by Tiger Woods supports the sales of PRP enormously. But it is more than just sales, it also makes the next ineffective treatment seem more likely to work, and diverts money from being used more effectively. Wouldn’t be a problem if you weren’t paying for it, but you are. Whatever health system you live under, you are contributing. It might be taxes, premiums or salary offset but trust me: you are paying for it.

Worst of all, it makes doctors look gullible and it shows how doctors can practice without  scientifically evaluating the available evidence. Sometimes without even being aware of the available evidence, except that supplied by the company rep. But embracing techniques that are later shown to be ineffective is what doctors do, and because of the stranglehold they have on public trust, they still manage to come up smelling like roses.

It is interesting to observe that much of the activity of skeptic organisations is directed toward alternative medicine – homeopathy, naturopathy, acupuncture, etc., based on the fact that they are practicing without scientific evidence. I think the skeptic organisations need to turn the spotlight onto traditional medicine for a while.

Addit, 22 June 2012:
A recent systematic review of 5 trials of PRP use in rotator cuff surgery in the shoulder concluded: "PRP does not have an effect on overall retear rates or shoulder-specific outcomes after arthroscopic rotator cuff repair".

Addit, 14 August 2012:
A 2012 systematic review of PRP in orthopaedic surgery concluded "there is uncertainty about the evidence to support the increasing clinical use of platelet-rich plasma and autologous blood concentrates as a treatment modality for orthopaedic bone and soft-tissue injuries"