**6. Transference of scientific knowledge to clinical practice persist in LAG**

One of the most important advantages of basic research is the possibility to transfer knowledge to improve clinical practice. However, in the case of PE, new information regarding new biomarkers and new opportunities of intervention emerge every year, but these are not implemented by the treating physicians. Moreover, clinical practice guidelines are lagging too, and many years pass before a new intervention reaches the level of recommendation within them. On the one hand, this occurs because the information that is generated seems to be isolated and fragmented, there is no body or work team or expert committee that focus their efforts on trying to solve the problem or on generating a line of research on the subject. Another part of the transforming knowledge problem is that for this to be carried out it is necessary that the information obtained may be applicable to different populations at different times and with different characteristics, this is very complex to achieve in the first place because, as mentioned previously, there is no focus group to this and separated efforts generate a bias in the study population. Another bias that impedes transfer is that the risk factors presented by each population are different in the developed countries than those in the developing world, so information generated on the one side is not necessarily applicable in other parts of the world. Because the origin of PE is not well understood, the approaches with which the different studies are developed differ, while some may determine that the cause is oxidative stress, some others may argue that the cause is genetic. The truth is that so far it is considered multifactorial and because of this the international guidelines are more discreet about which recommendations to accept, in the sense of being able to verify which actions will have an evident weight in clinical practice.

greater benefit, reason why stabilizing grades at first instance could help the obstetrician make a better clinical decision. Finally, although its justifiable not using a control group, this type of design (before and after), not having a reference group, leads to a lower internal validity [11]. In the study titled "Oral Progesterone and Low Dose Aspirin in the Prevention of Preeclampsia", the main inclusion criterion is having a history with preeclampsia. Nevertheless, other factors of high risk were not taken account. Even though the study propounds that a deficiency of progesterone could lead to PE and in consequence, supplementation with progesterone could reduce the incidence of PE, serum values as an indicator to identify patients whom could benefit with progesterone supplementation were not taken into account. The comparison

between before and after instead of vs the placebo group is also an inconvenient [11].

comparison against a placebo group, creating the same limitations [11].

ysis, because of premature termination of the study [11].

the study, which go unnoticed.

54 Clinical Trials in Vulnerable Populations

**in LAG**

In the study titled "Oral Progesterone and Low-Dose Aspirin in Preeclampsia Prevention," the main inclusion criterion is the antecedent of PE in previous pregnancies; however, as in the previous study, other factors that increase the risk are not taken into account. The study assumes that a deficiency of progesterone could be the cause of PE, this argument seems to be the rationale to reduce the incidence of PE using supplementation with progesterone; but in the study, they did not take serum values in consideration as a marker to indicate which patients could benefit from supplementation. This study, as the previous one, also lacks the

In the study entitled "Safety and Efficacy of RLX030 in Pregnant Women with Pre-Eclampsia" proposed by the company NOVARTIS did not have sufficient information to perform an anal-

In the study entitled "CPAP in Preeclampsia", the main objective is the evaluation of fetal wellbeing using nasal continuous positive airway pressure (CPAP) as a basis to increase fetal oxygenation; however, monitoring fetal movements is a scarce strategy to evaluate fetal well-being and it could be enhanced, according to the advances in fetal medicine to allow us to get closer to knowing the well-being of the fetus. The study did not make a distinction on the severity of PE, and if a clinical benefit of using CPAP is demonstrated, a distinction on the severity might

In several studies, narrowing gestational age as inclusion criteria perhaps increases internal

It is worth noting that the protocols registered in clinical trial go through variations during

One of the most important advantages of basic research is the possibility to transfer knowledge to improve clinical practice. However, in the case of PE, new information

be useful for clinical decisions. Therefore, the rationale to use CPAP is not clear [11].

**6. Transference of scientific knowledge to clinical practice persist** 

validity; however, the results cannot be extrapolated to other groups [11].

Finally, one of the most worrying aspects that delay the transfer of knowledge is the lack of medical update on the subject. A very obvious example is that in practice, physicians do not intentionally seek pregnancies with a high risk of PE, and when a patient is classified with high risk, the first action of the doctor is an expectant management, without any intervention, although in the guidelines of clinical practice the administration of acetylsalicylic acid, calcium, and l-arginine is recommended, this happens because evidence of acetylsalicylic acid's efficacy in reducing the risk is contradictory, while calcium intake is reserved for those women with low risk and low calcium intake, and l-arginine, although it is part of the Canadian guide, no dosage or time is specified.

Other evidence in the lack of management of the subject in some specialists is the lack of communication they generate with patients who are at high risk. Patients are not informed of their situation and expectant management "poor surveillance" continues even after the patient develops PE, which is when the symptomatic management begins, and it seems that the physicians are waiting for a complication to occur, to make the decision of taking a more active management. It is true that during the 1st weeks of the PE, there are not many recommendations, and that most focus on the final stages in which fetal viability can be achieved, but this same reason should be what drives medical doctors to have a closer monitoring in research opportunities and new information to improve the outcome of the pregnancy, remembering that once PE is presented, there is no curative treatment, beyond the interruption of pregnancy. Efforts should be directed at preventing the occurrence of PE or, failing at that, occurring late in pregnancy.
