It’s the Dose, Stupid

Author:

Seth Peterson, PT, DPT, OCS, FAAOMPT

The Motive Physical Therapy Specialists

Oro Valley, AZ

We learn from our failures more than our success. In other times, we learn from our “almost failures.” These close-calls are the best events to learn from, really, because they can carry almost the same weight as a failure without the tragic consequences. Police officers hint at their knowledge of this fact every time they let you go without a ticket. There is a hill on my way to work that I always brake while going down, 8 years later; It is a location where I got off with a ‘warning’.

When I think of “almost failures” in the clinic, I think of what I learned from my patient, Sarah (pseudonym). She was a glowing, bubbly middle-aged woman with a daily headache casting its shadow over her for about 6 months. She had been improving, but her improvement had stalled out over the past few visits. Her within-session change was consistent, but her between-session changes had stalled out. She was screened and cleared of “red flags.” Finally, we took a step back and analyzed her daily routine and her home program. Each exercise she was doing seemed to offer some benefit in reducing her pain when it was bad, but it did not eliminate it, and was getting less and less effective. We settled on one change: increasing the hold times in her “SNAG” stretch from 3 seconds to 30 seconds. Nothing fancy, but when Sarah came back, her headache was gone. I saw her at a Starbucks a few months ago and it was still gone. In her case, the difference between success and failure was 27 seconds.

It turns out that dosing is important. We all know that one ibuprofen might help but 100 ibuprofen is a bad idea. Chlorine in drinking water is okay, but too much in a swimming pool can aggravate your skin and drinking it can kill you. What is the appropriate dose for manual therapy or exercise? Moreover, are we doing a good job monitoring it?

What is Dosing in Physical Therapy?

When people talk about dosing, they are usually talking about the frequency, intensity, duration, and timing.¹ Dosing is seen as complex, and for good reason. Prescribing a dose of manual therapy or exercise requires you be able to assess the patient’s response to that dose or at least have a good understanding of what the outcome will be. The intent is to find the “therapeutic dose,” or the minimum dose that influences the patient’s symptoms without causing undesirable side effects. This can require some fiddling until the right amount is found. To track dose and response in manual therapy, it’s advised that we report:²

• The rate of force application (i.e. how fast were you moving the thing?)
• The location in range (mid-range or toward the end of the range, i.e. how much were you moving the thing?)
• Direction of force (i.e. where were you moving the thing?)
• Relative structural movement (i.e., what was moving?)
• Patient position.

It seems obvious that the time and frequency should also be recorded somewhere. With these basics, however, you can get a good idea about what the dose is and adjust that dose with time. With exercise, a similar thing may happen in physical therapy flow charts.

When Does Dosing Matter?

            The fact is, the dose typically matters. How much it matters depends on the situation. Of course, rehabilitation following stroke is an example where exercise dosing matters greatly.³ The frequency of physical therapy visits seems to be important in several orthopedic conditions, including spinal stenosis,⁴ neck pain,⁵ and knee pain.⁶ In manual therapy, they have found that higher forces are more likely to lead to better outcomes in neck pain⁷ and hip osteoarthritis,⁸ among others. When it comes to descending pain modulation, dosing also seems to matter, but can be achieved relatively easily through treadmill walking (at least in healthy participants).⁹

Other examples abound, such as the dose required for muscle hypertrophy versus muscle strength and maintenance versus improvement of that strength. Researchers have studied for decades the relationship between cardiovascular exercise and longevity and heart benefits. The fact is, dosing clearly matters, and we all know it.

Is Research Doing Dosing Wrong?

Despite its clear importance, dosing has not received much attention in the physical therapy research. For example, exercise dosing is wildly inconsistent for knee pain⁶ and likewise for manual therapy dosage for hip osteoarthritis.¹⁰ Despite us knowing that rehabilitation for spinal stenosis should consist of certain things (exercise, manual therapy, a walking program) and have a certain frequency,¹¹ studies continue to be performed that have no standardization whatsoever of nonoperative treatment arms.

Another factor to consider is that many prescriptive trials do not allow the treating physical therapist to adjust the dosage based on patient response. This is completely contrary to how patients are treated in the real world. If a patient like Sarah (mentioned previously) was enrolled in a trial, you have to think that she would have ended the trial with her headache improved, but still present. The thing is, there are numerous patients like Sarah. I shared an example on Twitter of another patient who got over a plateau after the intensity and direction of a manual therapy technique was changed.

One potential solution to this problem is the emerging concept of adaptive trial designs. In these designs, information collected during the study is used to adjust the treatment. For example, the trial may allow the physical therapists to adjust their dosing (within reason) when treating patients based on the response that patient has had (Figure).¹² These designs are very uncommon in physical therapy, although some researchers are beginning to plan trials using them.

Another consideration with research, and perhaps why dosing is all over the place, is because researchers often fail to identify the target of their intervention.¹³ I wrote about this in a previous blog post. Think about this from the perspective of dosing. If you are attempting to decrease someone’s pain, the dosage might be entirely different from if you are trying to improve his or her fear or physical functioning. Maybe you are trying to improve quadriceps strength in someone with knee osteoarthritis. Well, we have a good idea of the dosage required to increase strength in trained and untrained individuals. If we don’t know the dosage required to elicit a certain change, it makes sense for the researcher to do what clinicians would do and adjust it based on the patient’s response. This would seem particularly obvious for something like fear, which would seem to be highly contextual and individualized.

Conclusion

As a clinician trying to make decisions about patient care, we need to be clear in our thinking. Part of the reason that clear thinking is important is so we can reflect and learn from our “almost failures.” To do this, it is important to identify what you are trying to change in your patient and then to modify treatment based on the patient’s response. For some reason, research in physical therapy does not appear to be following the same line of thinking. It rarely identifies the target of treatment and usually doesn’t allow for adjustment of the dose based on patient response. The importance of dosing is already known to most of us, but for some reason physical therapy trials continue to dose interventions with a high degree of variability. When Bill Clinton’s campaign workers in 1992 were unsure what to focus their message on, James Carville is quoted as saying “the economy, stupid.” It seems just as obvious to me that making decisions based on research in physical therapy will never be quite as informative until more attention is paid to the elephant in the room: dosing. In other words, “it’s the dose, stupid.”

REFERENCES

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3. Klassen TD, Dukelow SP, Bayley MT, et al. Higher Doses Improve Walking Recovery During Stroke Inpatient Rehabilitation. Stroke. 2020;51(9):2639-2648. doi:10.1161/STROKEAHA.120.029245
4. Minetama M, Kawakami M, Teraguchi M, et al. Therapeutic Advantages of Frequent Physical Therapy Sessions for Patients With Lumbar Spinal Stenosis. Spine (Phila Pa 1976). 2020;45(11):E639-E646. doi:10.1097/BRS.0000000000003363
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8. Estébanez-de-Miguel E, Fortún-Agud M, Jimenez-Del-Barrio S, Caudevilla-Polo S, Bueno-Gracia E, Tricás-Moreno JM. Comparison of high, medium and low mobilization forces for increasing range of motion in patients with hip osteoarthritis: A randomized controlled trial. Musculoskelet Sci Pract. 2018;36:81-86. doi:10.1016/j.msksp.2018.05.004
9. Polaski AM, Phelps AL, Szucs KA, Ramsey AM, Kostek MC, Kolber BJ. The dosing of aerobic exercise therapy on experimentally-induced pain in healthy female participants. Sci Rep. 2019;9(1):14842. Published 2019 Oct 16. doi:10.1038/s41598-019-51247-0
10. Shepherd MH, Shumway J, Salvatori RT, Rhon DI, Young JL. The influence of manual therapy dosing on outcomes in patients with hip osteoarthritis: a systematic review. J Man Manip Ther. 2022;30(6):315-327. doi:10.1080/10669817.2022.2037193
11. Minetama M, Kawakami M, Teraguchi M, et al. Therapeutic Advantages of Frequent Physical Therapy Sessions for Patients With Lumbar Spinal Stenosis. Spine (Phila Pa 1976). 2020;45(11):E639-E646. doi:10.1097/BRS.0000000000003363
12. Pallmann, P., Bedding, A.W., Choodari-Oskooei, B.et al. Adaptive designs in clinical trials: why use them, and how to run and report them. BMC Med 16, 29 (2018). https://doi.org/10.1186/s12916-018-1017-7

1. Wood L, Bishop A, Lewis M, et al. Treatment targets of exercise for persistent non-specific low back pain: a consensus study. Physiotherapy. 2021;112:78-86. doi:10.1016/j.physio.2021.03.005