The era of trial and error medicine needs to be over | Critical care |

We always want to get it right the first time when treating patients, but the truth is this is difficult. When there is uncertainty of disease course and prognosis, multiple treatment options, and variable responses to therapy this becomes even more challenging.  Our typical strategy to making it “just right” isn’t too different from Goldilocks. We have mild treatments (too cold), and aggressive treatments (too hot), and even in the face of ambiguity, we need to start somewhere. This “trial and error” medicine can work, but we need to do better when the stakes are high, disease pace is rapid, and cost-effectiveness a major factor.


With chronic disease this is particularly hard.  As a provider, when I meet a patient late in the course of their disease it is easy to tell if they have had a mild course, or more complicated disease by learning what has occurred over the past 10 years. However, when meeting a patient soon after diagnosis — the course is uncertain, patients are not yet educated about the treatment options, and choosing therapy with which both provider and patient are comfortable isn’t easy. We could just quickly cycle through the options, like Goldilocks, but when the implications of using the wrong drug include rapid progression of their illness or significant potential treatment side effects, this is far from optimal.

For example, I am a gastroenterologist and my practice is dedicated to the care of people with Crohn’s disease and ulcerative colitis. For Crohn’s disease in particular, getting the first therapy right is critical. Crohn’s is a chronic inflammatory bowel disease that can cause complications including bowel narrowing (strictures) and rupture (perforation) of the intestine — both leading to surgery, sometimes even multiple surgeries. In people with the most aggressive disease – an ostomy (bag on the abdomen to collect stool) may be needed. These complications can occur within the first months after diagnosis or many years later.

Fortunately, many people with Crohn’s will never get a complication, and there is a broad range of disease severity. In fact, I am part of a research group called BRIDGe that set out to build an algorithm for how to manage patients with Crohn’s disease.  Even with trying to simplify the project, we identified 134 different “types” of Crohn’s patients we see in the office.  Since one size does not fit all, we realized that we can’t give a treatment guideline that fits all people with one disease, but that we need to treat them as individuals and make a personalized treatment plan. Guidelines are a nice starting point — but typically miss the nuances that are so important in getting it right for individuals.

Since tools to develop individualized treatment plans are not available most of the time, we are often left with making an educated guess. Providers often consider if they would rather be wrong under-treating or over-treating a disease process. Under-treatment typically avoids side effects and cost, but at the expense of a rapidly progressive disease causing more problems before we can get it under control — or sometime losing control completely. Over-treatment usually has a higher chance of working (stronger therapy), but at the literal and figurative cost of treatment, which may even include life-threatening side effects.  Engaging our patients in this decision making progress is critical, but exposing our uncertainty of the right thing to do may only make these big decisions more overwhelming.

As providers we are constantly working with our patients to make these difficult decisions. A typical presentation of someone with Crohn’s disease could be a 25 year old with abdominal pain, diarrhea and weight loss. The natural history of a patient like this could range from spontaneous resolution of symptoms to an emergency surgery with ostomy within 6 to 12 months. Using a mild drug like mesalamine will be reassuring to this patient and provider because it is safe and easy to take — but comes with a real risk of their disease progressing. The right treatment is probably more intensive therapy with a combination of a biologic drug (like infliximab) and a second drug (such as azathioprine).

The trouble is that although these are overall safe and effective, when reading about side effects of this treatment regimen, patients hear about things like cancer, tuberculosis and other life-threatening infections. Think about the last TV commercial you saw for one of these drugs — and that mumbling at the end that sounds like a side effect sub-machine gun going off.  If you are offered one of these meds — how can you possibly feel comfortable filling the prescription if you don’t understand if you really need it?

Progress is being made. Fortunately in a number of fields, mostly in cancer, we are starting to use genetics, blood tests, and patient characteristics to predict how a disease may behave and respond to therapy. In our work at Dartmouth we have built a tool to show patients with Crohn’s disease their individualized disease course so that they can consider this while reviewing the medication options they are being offered.

But progress is not being made fast enough. The pharmaceutical industry needs to fully invest in personalized medicine, even if this means fewer people will be ultimately eligible for their drug.  Academic institutions need to collaborate with industry to take medicine to the next level. The era of trial and error medicine needs to be over.  It is time for Goldilocks to have the thermometer that would have allowed her to get it “just right.”

By the way, the first publication of the story of the Three Bears in 1838 appeared in the collection of prose called The Doctor. Way ahead of their time.

Via Technical Dr. Inc.