Motherisk and Canadian Family Physician

Not supported by best evidence

The first question is relatively straightforward to answer. We agree with the conclusions of Persaud and his colleagues that there is not, at this time, clear evidence that the combination of doxylamine-pyridoxine is more effective in the management of NVP than pyridoxine alone and that the grade IA evidence recommendation in the Motherisk guidelines published in CFP and by the Society of Obstetricians and Gynaecologists of Canada is not supported by the current best evidence.⁵ Although in July 2016 Health Canada published a review of the safety of doxylamine-pyridoxine and concluded that its benefits continue to outweigh its risks when used as authorized,⁷ family physicians treating NVP could consider pyridoxine alone as first-line therapy. This recommendation is consistent with clinical practice guidelines from the United States⁸ and Australia.⁹ Family physicians could also consider following the recommendations from the National Institute for Health and Care Excellence¹⁰ or the Royal College of Obstetricians and Gynaecologists¹¹ in the United Kingdom, which recommend antihistamines alone.

Reflection on a long-standing relationship

The answer to the second question is more complex and deserves close scrutiny.

The relationship between CFP and Motherisk dates back 2 decades. No written record of the beginning of this relationship exists, but it is almost certain that, at the time, Canadian family physicians were looking for the best available evidence about the safety of prescription and nonprescription drugs for their pregnant patients. Motherisk was then perceived as a highly reputable organization dedicated to answering just such questions, and CFP thought it appropriate to help facilitate Canadian family physicians’ access to that information.

Over the past year or so the reputation of the Motherisk organization has been called into question as a result of concerns about the potential influence of Duchesnay, the manufacturer of Diclectin, the combination of doxylamine-pyridoxine, on the Motherisk NVP guidelines.¹²

Canadian Family Physician ended its long-standing relationship with Motherisk at the end of 2015. In part this was because of the concerns about the independence of the organization from industry raised by the work of Dr Persaud and his colleagues. The editorial staff and the Editorial Advisory Board of the journal reflected deeply on the issues raised by its long-standing relationship with Motherisk. Several lessons have been learned, which we wanted to share with our readers.

Influence and integrity

It is impossible to know to what extent the recommendations for the management of NVP in the guidelines were directly influenced by Motherisk’s relationship with a pharmaceutical company, but there is widespread influence of industry on the creation of clinical practice guidelines in medicine.¹³ Furthermore, reputable advocacy organizations like Motherisk might be especially attractive and susceptible targets for such influence.

It is important for us to recognize that CFP added to the validity of the NVP guidelines by reinforcing the credibility of Motherisk, allowing it a privileged place in the journal. Unlike most other manuscripts submitted to CFP, Motherisk articles were not subjected to a full double-blind peer-review process. This was based on assumptions about the quality of the work and the integrity of the organization. This approach was allowed to persist over the intervening years until the more recent concerns arose.

Evidence is not static

As generalists, family physicians will continue to use clinical practice guidelines, most of which are currently developed by non–family physician specialists or disease-specific organizations. In doing so we must take the best available evidence as we know it and apply it in our practices, but be constantly aware that we might be wrong or that the evidence might be flawed.

Would a more formal double-blind peer-review process have detected the problems with the Motherisk NVP guidelines? It is hard to know with certainty. It was only through a thorough re-evaluation of the literature, prompted by questions from a patient to a family physician researcher, that led to this discovery. Evidence is not static; re-evaluation of accepted truths should not be seen as a weakness as new information comes forward.

Canadian Family Physician will likely continue to have ongoing relationships with different organizations or institutions if these best serve the information needs of family physicians and their patients. However, this episode is a clear lesson that we must do so with greater scrutiny, with more formal agreements, and only with those that do not have any ties to industry or other entities that would create, or even appear to create, information or guidelines that have a purpose other than clear and science-based benefit to patients in our care.

Science and journals such as CFP that publish science in service to good care are not static entities. They are human endeavours dedicated to discovery and application of knowledge and have the imperfections that all human endeavours will demonstrate from time to time. It is vitally important to learn from those imperfections rather than deny they exist. We began with a quote from history underscoring the need for humility in all things. We close with words put in the mouth of Galileo by Bertolt Brecht in his eponymous play: The aim of science is not to open the door to infinite wisdom, but to set a limit to infinite error.Bertolt Brecht, Life of Galileo