Effect of home-based "Kangaroo Mother Care” on infant intake of breast milk, intestinal inflammation, and signs of mothers’ birth depression and stress

Saksnr. NEM 2019/114, REK Vest 2019/31 | [Complaint]

Universitetet i Bergen

Halvor Sommerfelt 

REK vest

Appeal against the decision by Feb.19th 2019 where REC West rejected application for post-approval of the subproject. The subproject was submitted for approval at first, but REC found that the project was started in 2017 and the application had to be considered as an application for post- approval.

This is a subproject of a project that has been evaluated and approved by REC in 2015 (2015/1486). The main project was approved as a randomized controlled trial of the effect of kangaroo mother care method on early child deaths in India. In the subproject the aim is to explore the effect of (KMC; skin-to-skin contact and exclusive breast feeding) on intake of breast milk, infant gut inflammation and postpartum depressive symptoms.

REC West found that the conditions for post-approval was not fulfilled and denied approval of the study.

The Principal Investigator appealed the decision on March 3rd 2019. The main reasons for appeal are as follows:

The protocol for the main project states that sub-studies will be applied for to a local REC. In case of a discrepancy, the wording in the protocol has priority over the wording in the application form. In accordance with wording in the protocol, the project has received approval from at local Indian REC.

REC considered the study to be of interest and had no remarks to the quality of the project, but still considered that the conditions were not met. REC forwarded the case for considerations to The National Committee.

With some doubt, The National Committee considers that the condition of “good faith” is met. The committee considers that the study should be approved.

Kangaroo Mother Care promotes survival in low birth weight infants through mechanisms yet to be elucidated. A large trial in India estimated the effect of community initiated Kangaroo mother care (ciKMC) on neonatal mortality. Within the trial, PhD student Bireshwar Sinha assessed the impact of ciKMC on infant breast milk intake, maternal postpartum depressive symptoms, a biochemical marker of maternal stress, and infant gut inflammation.

Infant breast milk intake is measured by a stable isotope method using salivary samples. Maternal depressive symptoms were identified using the Patient Health Questionnaire (PHQ-9) and salivary cortisol levels were measured to reflect maternal stress.

The primary objectives of the PhD studies are to estimate the effect of ciKMC on: 1. infant milk intake 2. prevalence of moderate to severe postpartum depressive symptoms and salivary cortisol levels 3. Gut inflammation as reflected in levels of fecal neopterin, myeloperoxidase, alpha-1-antitrypsin.

REC west has considered for afterwards approval in the committee Feb.6th 2019.The project is a substudy of a project that has been evaluated and approved by REC in 2015 (2015/1486).The sub-study was submitted for approval by Jan. 8th 2019. REK found that the project was started in 2017 and the application had to be considered as an application for post approval.

The rule of the Health Research act is that application for ethical approval of health research projects shall be submitted and approved before a project is started, Health Research act § 10.

It is, however, possible to get an afterwards approval, but on strict conditions, which are that

a) at the project start there was doubt whether the project is applicable to the REC;

b) the principal investigator was in good faith to whether the project was applicable to the REC;

c) the mistakes committed in the process were minor and not serious;

d) there are no reasons to think that the project would not have been approved if applied for at the right time;

e) consideration to the research participants suggests that one should proceed and fulfil the study.

REK west found that the conditions for afterwards approval was not fulfilled and denied approval of the study. The Principal Investigator appealed the decision on March 3rd 2019. The main reasons for appeal are as follows: The protocol for the main project states that sub-studies will be applied for to a local REC. In case of a discrepancy, the wording in the protocol has priority over the wording in the application form. In accordance with wording in the protocol, the project has received approval from at local Indian REC.

The PI considered that the Norwegian REC, by approving the main study, also had approved that a sub-study could be approved by a local REC. The PI considered himself in good faith and that approval from a Norwegian REC was unnecessary in view of the Indian approval. The PI also points out that there is no doubt that the study may be of use to other low births weight babies, and therefore believes that the project would have been approved if it had been applied for before it was started. There is also no doubt that the study is of great use for the participants. In addition, the PI argues that the lack of approval from Norwegian authorities could have been prevented if it was not for the institution’s lack of routines.The PI therefore believes that the conditions for an afterwards approval are fulfilled and asks that the decision to deny approval on grounds of too late application is changed.

REC considers the study to be of interest and has no remarks to the quality of the project, but still considers that the conditions are not met. The decision states that amendments to the main study shall be submitted to REC via the amendments form. This of course indicates a Norwegian form and a Norwegian REC. This consequently rules out good faith.

The lack of routines in the institution cannot be an argument for an afterwards approval.

REC has also considered this case in the light of an earlier changed decision by the National Committee but finds that the considerations in that case is applicable to this study.

In a meeting April 10th 2019, the REC declined to change the decision, and forwarded the case to The National Committee for considerations.

The Committee takes the case into consideration, referring to the act on ethics and integrity in research § 10 subsection 3, and the public administration act § 34.

According to the health research act § 10, a health research project shall be approved by a REC before the project starts. It is, however, possible after a concrete consideration, and as an exception, to approve a project after it has been started. The conditions for doing so are meant to be strictly interpreted.

The Committee agrees with REC that this project should have been submitted for consideration for prior approval by a REC, as stated in the Health Research act § 10. The case therefore is about whether the conditions for an afterwards approval are met. The Committee also agrees that the lack of routines by the institution cannot be a basis for any precedence for afterward approval. It is also the responsibility of the PI to know the laws and regulations.

The Committee also agrees with the REC that the case «Registerbasert studie av tidstrender i svangerskapsutfall i Tanzania», where the RECs decision was changed by The National Committee, is not applicable to this case.

The Committee has considered the case by the same criteria for afterwards approval as the REC, but have assessed the conditions differently. The main study is approved by a Norwegian REC and the sub-study is approved by a local Indian REC. This means that the procedures described in the protocol for the main study are followed by the project. Therefore, the Committee considers the fault of the project to be minor and of no consequence for the participants.

There is no report concerning problems with the main study, and there is no reason to believe that the sub-study would not have been approved.

Low frequencies of breast feeding and under nourishment are big problems in many countries, and the usefulness of the study for society is of no doubt. In this case, the participants also have a highly probable use of participating in the study, and it must be considered a disadvantage to discontinue the study.
In addition, the Committee notices that in the protocol of the main study is a sentence which indirectly points to this sub-study. The PI argues that he has misunderstood that «must be approved by REC» meant a Norwegian REC, not a local Indian one, and therefore have believed that when the main study was approved by a Norwegian REC, this meant that sub-studies could be approved by Indian RECs. As such approval is given, this suggests that the PI has related to the understanding he maintains.

With some doubt, the Committee considers that the condition of «good faith» is met, although one has a certain degree of sympathy with REC's interpretation.

In the Committees view, it is not necessary that all the conditions for afterwards approval are met at the same time. Consequently, the Committee considers that the study should be approved.

The appeal on REC west’s decision not to give an afterwards approval of the sub-study “Effect of home-based «Kangaroo Mother Care” on infant intake of breast milk, intestinal inflammation, and signs of mothers’ birth depression and stress”, is accepted.

The project is approved according to the health research act § 10.

According to the new personal information act and GDPR article 24, the controller, i.e. the head of the institution, must be able to demonstrate that the processing of information in the project is performed in accordance with the Regulation.

If substantial changes in the project are to be made, an application must be submitted to the REC that has granted the prior approval.

The project manager must submit a final report to the regional committee for medical and health research ethics when the research project is finished. The final report must present the findings objectively and methodically, ensuring that both positive and negative findings are presented.

The approval is valid until December 31st 2023. The project manager must submit a final report to the regional committee for medical and health research ethics within six months after the research project is finished. Information that are necessary for auditing the project can be kept until 2028.

The Committee’s decision is final and cannot be appealed.