Thursday, 26 April 2012

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

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, 12 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 Marx 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, 5 May 2014:
A recent Cochrane review of PRP in soft tissue musculoskeletal injuries concludes that there is insufficient evidence to support the use of PRP.

12 comments:

  1. THe first clue to core of the problem is in the phrase "if doctors were really scientific . . . " Somehow doctors get this idea, even though many haven't the first clue what science really means. Here in the U.S., getting into medical school generally means getting good grades in college science classes, but that doesn't necessarily mean the student has actually learned to think like a scientist -- and it certainly doesn't mean they have learned to look at a clinical trial and take it apart, to look for validity. Is that the case in Australia?

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    1. Exactly the same, I'm afraid. The deficiency in structured teaching of critical thinking is a problem for universities across the board, and you would think that if universities were to teach ANYTHING, it would be that.

      Many doctors are amazingly unscientific. I ought to know: I was (and I still struggle).

      For those interested in learning, I recommend a website devoted to teaching doctors the principles of critical thinking (https://sites.google.com/site/skepticalmedicine/).

      Thanks Shannon, for your support. And I loved your book, by the way.

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  2. What's the harm with charging the poor folks with tendonopathies $500 dollars out of pocket for an injection? Like you said, if all of those famous athletes are getting it, I want it too. Just like I want the same day MRI for my fill-in-the-blank-joint pain like the pro's do too.

    Dr. Skeptic, I just wish we could REALLY, and I mean REALLY, convince the public that all of the arguments against using evidence based medicine are bogus and whether intentional or not, are self-serving those interests and not the patients'.

    I worry that when we sound the alarm about spending money on things we don't need, or harmful things, or doctors doing too many non-indicated stents or knee scopes etc... that we get lumped with the anti-science people, the anti-vaccination crowd and the like.

    It really stinks when we do have things that are helpful but then get bastardized by overuse (eg stents do save lives during heart attacks but not at any other time).

    Thanks for your hard work.

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    1. Thanks Michael - all good points.

      I think the way to avoid being lumped with the anti-science leagues (for want of a better term) is to be scientific: weigh up each treatment on its merit. Be critical of ineffective treatments and accept the good treatments (and I agree that there are good treatments out there, I just don't cover them in this blog).

      As far as the cost, this is a common question. I really don't mind if somebody wants to pay for placebo treatment. As long as they are made aware of the evidence, and as long as I am not paying for it indirectly (premiums, taxes, etc.). There are millions of people around the world paying a lot of money to healers of all types, for nothing more than placebo. I only have a problem if it is harmful, or if I am (or society is) paying for it.

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  3. Replies
    1. A treatment has to be pretty bad to not work at all. Comparison with placebo is the real test of a specific therapeutic effect, and in that regard, PRP fails.

      Things that 'work' like that are commonplace in the medical world. I accept that PRP works. I object to the claim that there is a specific effect, and I object to paying for it.

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  4. I've been digging through articles and posts on PRP for a few days in hopes of finding something relating to what I'm hearing it recommended for for my wife. Back problems: Specifically lower back with degenerated, bulging, and torn discs.

    Almost everything I'm finding on it is related to Sport Medecine, but one article mentioned it being used for back/spine issues(or similar) since the 90s, but questioned efficacy for sports medicine use (which seems to be the universal result for PRP as Sports Medicine). Neither it, nor any other I've seen, seems to say it does or doesn't work for the spinal issues.

    Any thoughts? insights?

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    1. Thanks Charles,

      PRP is largely ineffective for any condition, compared to placebo. I am not aware of any such trials in the spine. Nor does it make any sense.

      Back pain is common, the association between pain and severity of degenerative changes is weak, and treatments aimed at reversing age-related changes are fighting nature. Looking for a 'cure' might not be the best way to direct your energies. Learning to deal with the symptoms and being reassured that it is not dangerous might be better.

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  5. i have had adductor tendonitis for the last 15 months and tried everything from rest,physical therapy and cortisone injections and got a prp injection 5 weeks ago. i was told to rest for 5 weeks and returned to my doctor for a consultation. i was told my tendon had healed and i could start swimming at this point. the injection seemed to reduce my pain dramatically but once i went jogging in the pool the pain returned but not as bad as before. why is this?

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    1. Conditions fluctuate. When you rest they often get better (like you did after the injection) and when you exercise they often get worse. All I can say is that the probability of the PRP injection doing anything directly is very low.

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  6. Can prp be used for skin rejuvenation specifically for removing dark circles around the eyes?

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    1. Yes it can. This is one of the many things that PRP is used for.
      Whether it works, though, is a different matter. It is most likely that it will not work any better than placebo for just about anything.

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