The science surrounding vitamin D presents both challenges and opportunities. Although many uncertainties are associated with the understandings concerning vitamin D, including its physiological function, the effects of excessive intake, and its role in health, it is at the same time a major interest in the research and health communities. The approach to evaluating and interpreting the available evidence about vitamin D should be founded on the quality of the data and on the conclusions that take into account the totality of the evidence. In addition, these activities can be used to identify critical data gaps and to help structure future research. The Office of Dietary Supplements (ODS) at the National Institutes of Health has as part of its mission the goal of supporting research and dialogues for topics with uncertain data, including vitamin D. This review considers vitamin D in the context of systematically addressing the uncertainty and in identifying research needs through the filter of the work of ODS. The focus includes the role of systematic reviews, activities that encompass considerations of the totality of the evidence, and collaborative activities to clarify unknowns or to fix methodological problems, as well as a case study using the relationship between cancer and vitamin D. Vitamin D remains a major research focus. No doubt there is great interest in the question of vitamin D, ranging from the reason for the presence of its receptors in many body cell types, to the relationship between intake and overall health outcomes. Vitamin D is a component of the diet, but it is a unique nutrient in that it functions as a prohormone, which may be endogenously produced under conditions of sun exposure. Regardless if whether obtained from food, supplements, or sun exposure, it functions similarly in the body and must undergo further processing by the body in order to become the physiologically active hormone . The active hormone has potent cell signaling abilities and is tightly regulated at the tissue level.Yet, there remains considerable uncertainty surrounding vitamin D—a nutrient that is characterized by emerging science. Despite much conjecture about its role beyond bone health, the science does not reflect an agreed-upon trajectory for many conclusions about vitamin D. Some have identified vitamin D as a notable nutrient that is responsible for many benefits that are associated with reducing chronic disease risk, and some advocate for greater health through a increased consumption of vitamin D. Yet, others conclude that the interest surrounding vitamin D may be similar to an earlier experience, which is referred to as the “beta carotene phenomenon”, in which supplementation with beta carotene  was initially purported to be beneficial and widely recommended. Subsequently—after clinical trials—beta carotene was found to have unanticipated detrimental effects or a spurious benefit. In any case, it is evident that the science surrounding vitamin D is far from settled. At the same time, research continues to accumulate. A key question is how such data are evaluated, enhanced, synthesized, and incorporated into scientific conclusions and related recommendations about vitamin D so that these are reasonably stable over time and ensure public confidence in health guidance. The Office of Dietary Supplements (ODS) at the National Institutes of Health (NIH) has a mission to foster dialogue and research related to scientific uncertainties. During recent years it has worked to address vitamin D, both as a supplement and within the context of total exposure. The underlying interest of the office is to encourage the development of systematic reviews along with consideration of the totality of the evidence when reviewing the science surrounding vitamin D. An additional ODS focus has been collaborative activities to support research and foster improved methodologies and scientific understandings. These activities reflect the types of efforts that help to deal with uncertain data, identify knowledge gaps to be addressed, and work to move the science to the next step. The systematic review process within the field of nutrition has been described by others ,5. BriefSystematic reviews evolved from the field of clinical medicine, for which questions tend to be more straightforward than issues related to nutritional topics. Nutritional questions are by their nature more complex because there is often a high degree of uncertainty as well as considerable variability among nutrition studies. In short, there may be considerable data on a specific nutrient, but cumulatively the data do not lend themselves to merging for increased statistical power . For theThe development of nutrient reference values illustrates the nature of the steps that are necessary to ensure that the totality of the evidence is taken into account when making scientific conclusions or underpinning public health recommendations, an approach that is central to the ODS perspective on addressing emerging science. In the United States and Canada, reference values, known as Dietary Reference Intakes (DRIs), are established by expert committees that are convened by the Institute of Medicine (IOM), now the National Academy of Medicine. The approach used by the IOM to establish vitamin D reference values demonstrates a process that takes into account the totality and strength of the evidence ,11. The In 2008, ODS and other federal sponsors co-funded IOM’s efforts to convene an IOM committee to establish DRIs for vitamin D, as well as calcium, with a final report being issued in 2011 . The comFor ease of its consideration of the totality and strength of the evidence, data can be arrayed in a variety of ways. Using fractures as an example of integration, the types of summaries from systematic evidence-based reviews that were important to the committee’s conclusions are highlighted in The committee next focused on specifying a dose-response relationship between serum 25(OH)D concentrations and bone health based on the identified measures. Compiling and integrating data led the IOM committee to conclude that the strongest evidence linked a concentration of 16 ng/mL (40 nmol/L) serum 25(OH)D to an average requirement for bone health , the valFinally, the committee specified the total dietary intake that is needed to achieve the EAR- and RDA-linked values for serum 25(OH)D concentrations . Newer sA goal of DRI development is to ensure that the conclusions can stand the test of time. That is, reference values should be based on endpoints with data that are not likely to be quickly reversed with a few additional studies. As an example of this concern, at the time of the committee’s work efforts to link the relationship between reduced risk of falls in older individuals and high doses of vitamin D (presumably due to improvements in muscle strength and lower extremity function), was gaining momentum that was based on both observational data and clinical trials. The committee considered that the available evidence was derived from small, underpowered randomized trials, and appeared to be contradictory among the observational data ,13. In 2Reference values are also established by authoritative bodies in other countries, including the Scientific Advisory Committee on Nutrition (SACN) in the United Kingdom and the European Union’s European Food Safety Authority (EFSA). Comparison of the IOM outcomes for vitamin D with those from SACN  and EFSAFinally, the effort to establish DRIs highlighted data gaps in the field of vitamin D research that are particularly germane to the process of establishing nutrient requirements. Examples of these are shown in Science, of course, continues to advance. An important factor in arguing for further research relative to vitamin D is the notable expansion of interest in the topic given the many receptors in the human body coupled with the mixed nature of available data to date, the number of health benefits that have been hypothesized, the numerous confounding factors that complicate interpretation of the data, and its unique role as a nutrient that is also a hormone. The topic of cancer and vitamin D illustrates the continued progression of understandings that have evolved following the development of DRIs and the need for further research, and, in turn, it serves to reflect similar needs for other vitamin D health relationships. 2D) may be protective against cancer. To date, preclinical studies usually have demonstrated the protective effects of vitamin D against cancer through the modulation of many different molecular targets and biological processes that are dysregulated during carcinogenesis, including cell proliferation, apoptosis, inflammation, cell differentiation, angiogenesis, invasion, and metastasis [The hypothesis that vitamin D might exert cancer protective effects was first suggested 30 years ago by ecologic or geographic correlation studies, which demonstrated lower cancer mortality in regions with greater exposure to solar UV-B radiation ,18. Becatastasis . Similartastasis ,21. In ctastasis . p = 0.88). The authors of this analysis concluded “There is currently no firm evidence that vitamin D supplementation decreases or increases cancer occurrence in predominantly elderly community-dwelling women [This disparity between the preclinical literature on vitamin D supplementation and cancer and the epidemiologic literature on vitamin D status and cancer can best be resolved by randomized controlled trials investigating the relationship between vitamin D supplementation and cancer. A Cochrane review was conducted to assess the beneficial and harmful effects of vitamin D supplementation for the prevention of cancer in adults . Eighteeng women .” HoweveVITamin D and OmegA-3 TriaL (VITAL) and D-Health have been successful in recruitment [Internationally, four large  randomized controlled trials that are investigating the effect of vitamin D supplementation on the primary prevention of cancer can be found in clinical trial registries  23,24,2,26. Whilruitment , and it The VITAL study , which wAt baseline, 16,956 participants or 65.5% of the total study population provided blood samples . Blood sIn addition to assessing total 25(OH)D concentrations of subjects, the VITAL study is also assessing other potential 25(OH)D-related measures of vitamin D status. The VITAL study investigators plan to use a nested case-control study to measure vitamin D binding protein and free 25(OH)D and to calculate the bioavailable 25(OH)D. It will comprise 2000 incident cases of cancer and cardiovascular disease and 1000 controls, and will assess whether baseline levels of these emerging measures are related to the risk of these outcomes or modify the effect of the vitamin D intervention. Thus, as an important example of efforts to advance understandings about vitamin D, the VITAL study should clarify a number of gaps in the literature, such as whether vitamin D supplementation is protective for the primary prevention of cancer, whether there are ethnic differences in the relationship between vitamin D supplementation and cancer risk, what is the relationship between baseline vitamin D status and the response to vitamin D supplementation and subsequent cancer risk, and what is the utility of evolving biomarkers of vitamin D status. Efforts both to clarify the basic biological activities of vitamin D and to enhance the applicability of the existing research are often at the forefront of discussions about vitamin D. As funding allows and in collaboration with the institutes and centers at NIH, ODS supports research on topics related to dietary supplements, including vitamin D. Proposals from interested parties are solicited via program announcements, requests for applications, and other mechanisms. A complete listing of ODS co-funded grants can be found on the ODS website . As illuAlthough such grants help to build an important foundation for conclusions about vitamin D, ODS also works to enhance the multiplier effect, which expands and enhances collaborative and follow-on research and activities. This includes dialogues to identify and increase awareness of research needs and knowledge gaps, such as a 2014 conference on evidence-based decision making for vitamin D in primary care , as wellLeveraging expertise is an important component of addressing uncertainties, especially given the reality of limited resources. One such ODS-driven collaborative activity is the Vitamin D Standardization Program (VDSP). Currently, there is an international debate regarding the interpretation of serum 25(OH)D concentrations, especially related to questions of dose-response and to determining status ,15,29. ATo address the problem of assay variation, ODS established VDSP in 2010 with the objective to promote the standardized measurement of 25(OH)D worldwide . The VDSA standardized laboratory measurement is one that is accurate and comparable over time, location, and laboratory procedure. In this context, the standardized measurement of 25(OH)D is one in which all of the laboratories using different assays at different times and in different locations obtain the same results—within specified statistical criteria—for the same sample . MoreoveTo accomplish the goals of standardization, the VDSP, sponsored by NIH/ODS, has worked with its collaborators to assemble a set of tools that can be used to standardize 25(OH)D measurements now and in the future . Those tAt these point standardization programs nearly always stop. However, given the wealth of published data, ODS and its collaborators considered it important to standardize 25(OH)D data from national health surveys, clinical trials, and other key completed studies where properly banked serum samples exist ,39. ThusIn any field of study, emerging science with its surrounding uncertainties will offer an array of challenges relative to interpretation and application in the public health arena. Perhaps one of the most important lessons to be learned in addressing emerging science is the need to be clear about its nature—its strengths and weaknesses—and to be clear about what is needed to clarify the questions that it raises. The natural tendency to rush to strong conclusions should be avoided when based on limited or contradictory data that are available or on data that are appealing. Rather, the goal should be to make the best conclusions given the totality of the evidence that is appropriately caveated and presented in a transparent manner. Likewise, the desirable research strategy is to actively identify the specific data gaps and systematically work to close them. Vitamin D—and the work of the ODS—offers examples of how such strategies can be employed.In addition to those data gaps identified in


Several factors have made hepatectomy an increasingly safe surgery and new drugs allowed surgical treatment for patients who initially were not candidates for resection. Lesions often require resection, which can be performed by open, laparoscopic, or robotic assisted hepatectomy. Compare the surgical techniques in open, laparoscopic, and robotic assisted hepatectomy for resection of liver tumors. Literature review based on scientific papers published on Lilacs/Pubmed/Scielo in the last 17 years regarding the indications of these techniques for liver tumor resections and on papers comparing such techniques. The comparative study shows the benefits of laparoscopic surgery over open surgery, such as smaller incisions, less postoperative pain, shorter recovery time, smaller immune and metabolic response, and quicker restoration of oral ingestion as well as lower morbidity rates. However, the need for a specialized surgical team and the reduction in handling area still remain as disadvantages in the laparoscopic technique. It is yet not clear whether robotic assistance presents considerable benefits over the laparoscopic technique considering that high acquisition and maintenance costs are limiting factors.Despite all challenges, laparoscopic hepatectomy presents many benefits over open surgery. The robotic assisted technique is still in evolution as many centers in the world perform hepatic resections with the platforms but only after a thorough patient selection. Thus, laparoscopy stands as the best option, unless there is some contraindication to the procedure. Over the last years, several factors have made hepatectomy an increasingly safe surgery. A better knowledge of liver anatomy, the development of imaging techniques, a more complete preoperative assessment of the patient and his liver function with multidisciplinary work as well as the improvement in surgical and anesthetic techniques have contributed to thisAccording to Lopes-Junior et al. (2014), some strategies have been developed to increase the resection rate in patients with liver primary tumors and metastases. As chemotherapy evolved, new drugs were developed, mostly for treatment of metastases, providing better responses and allowing surgical treatment in patients who initially were not candidates for resection.Hepatic lesions can be benign or malignant and both may require resectionThe National Cancer Institute (INCA) develops yearly an estimate of cancer incidence in Brazil. The Estimate/2014 doesn’t present data regarding liver and biliary tract cancer but highlights the importance of these lesions due to their high lethality and sensitivity to preventive actions, such as immunization coverageAs for the workup, tests such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), angiography, and biopsy can be performed to aid in the diagnosis of liver cancer.Surgery is the best treatment for primary liver tumors without distant metastases and metastatic liver tumors in which the primary lesion was resected or is likely to be resected in a curative way. The indication for hepatic resection depends on the clinical conditions of the patient and the expected amount of remaining liver parenchyma, which should be around 10% of the patient’s body weight. In cirrhotic patients, only the ones with a Child A classification (early cirrhosis) are candidates for safe liver resectionAnother possible treatment is liver transplant, but only a small proportion of patients are good candidates for it since the criteria is based on the size and number of tumors. Currently, transplants are indicated for small tumors - three or less nodes up to 3 cm each or single nodes up to 5 cm in which there was no invasion of blood vessels or for cases where the tumor cannot be completely removed or the liver is too far compromisedSo, the aim of this article was to compare the surgical techniques in open, laparoscopic, and robotic assisted hepatectomy for resection of liver tumors.This literature review is based on scientific papers published regarding the indications for open, laparoscopic, and robotic assisted hepatectomy in resection of liver tumors and on papers comparing these techniques. The research was conducted using the databases Lilacs/Pubmed/Scielo with selection of articles published in the last 17 years related to the topic.A correct preoperative prepare must take into account the nature of the liver disease, its severity, and the type of operation to be performedThe assessment of liver function is essential and the classification of Child-Turcotte-Pugh is the simplest form to do that. Even small liver resections are not possible in most patients with B or C stages of this classificationThe presence of portal hypertension  should always be evaluated since it is a better predictor of bad prognosis than the Child-Turcotte-Pugh criteria in patients undergoing liver resectionsThe MELD (Model for End Stage Liver Disease) score, which uses INR, creatinine, and bilirubin levels, can also be used as a pre-surgical evaluation parameter. What favors the use of this score is the fact that it is continuous, being performed numerous times throughout patient care. A reduction in the score indicates that the patient’s condition has improved, being, thus, possible to recommend the surgical procedure once the MELD is below 10. When the MELD score is between 10 and 15, surgery should be performed with caution and only when strictly necessary. In people with a MELD score above 15, surgical procedures are not recommendedThe preoperative preparation can also include fasting, indwelling urinary catheter, prophylactic antibiotics , and two peripheral venous access, varying among casesThe open operation is performed with the patient in a supine 15º Trendelenburg position with the right arm at a 90º angle. The surgical incision is made across the superior abdomen, following the curvature of the ribs. It can be bilateral subcostal for larger resections or only extended to the left for minor resections. When the mass to be addressed is very large, one can combine access between the abdomen and the chestThe use of intraoperative ultrasound is essential to identify the location of the nodules during surgery as well as their relationship to the blood vessels of the liver. It is also possible to identify new nodules not visualized on CT or MRIIt’s important to consider bleeding control methods, especially the Pringle maneuver  and total hepatic vascular exclusion . After vascular control, the compromised part of the liver is removed. At the end of surgery, a drain may be left near the area where the liver was cut to monitor bleeding and bile leakage14, 2, 9.The extent of the resection depends on the hepatic function of the patient. If there is no cirrhosis up to two thirds of the liver can be removed surgically. When lesions are large, patients must undergo, whenever possible, major liver resection, which is related to an increased progression-free survivalThere is no consensus regarding the optimal surgical resection margins. Some studies show that segmental resections of any segment or sector where the tumor is located, including its portal pedicle, showed better results than enucleations but other papers do not demonstrate this superiority. Several studies show that resection margins larger than 1 cm are associated with higher survival ratesWhen there is macroscopic vascular invasion, resection is contraindicated, as this is known to be a poor prognostic factor associated with high recurrence and an overall survival rate of less than 10%The surgery lasts 3-4 h and the patient must stay in the ICU (24 h) for monitoring of bleeding and liver function, returning to the ward when stable. After this, the patient may remain hospitalized for as much as 10 days. After surgical removal of part of the liver , the remaining tissue starts to regenerate 48 h later and reaches a size similar to normal within 3-4 weeks. The function returns to normal in about 6-8 weeksThe most common clinical complications are pneumonia, deep vein thrombosis, pulmonary embolism, and liver failure. Regarding surgical complications, bleeding and bile leakage on the liver resected surface can occur. It’s important to note that liver resection has a high tumor recurrence rate of up to 50%. This may be related to metastasis of the resected tumor or to the appearance of new foci since the remaining hepatic parenchyma remains diseased. However, hepatic resection preserves the possibility of liver transplant, ablation techniques, or following resections in cases of recurrenceThe most common contraindications for surgery are: patients with compromised cardiopulmonary function, severe malnutrition, impaired liver function, extrahepatic metastatic disease, and invasion of the portal vein bifurcation or of the hepatic veins trifurcationHepatic resection through open surgery was the treatment of choice for many years but was limited due to high rates of morbidity, mortality, and recurrence of the underlying liver diseaseSome advantages of hepatic resection that can be cited are: a) immediate availability in specialized center; b) low risk in well-selected patients; c) precise histological evaluation; d) overall survival rates comparable to those with the intention of transplanting; e) possibility of rescue liver transplant in cases of relapse, as long as patients are monitored closely for early diagnosis of recurrences; and f) reduction of costs on the global economy of liver transplantThe technical advances in laparoscopy have revolutionized surgical treatment for many diseases. In recent years, these advances have enabled video-assisted resection of solid organs such as the kidney and the spleen. However, some surgeries, such as liver resection, are still viewed with skepticism, since factors such as the transection of the parenchyma, the potential for intra-operative bleeding, and the risk of air embolism make the procedure a controversial themeLaparoscopic hepatectomy is a difficult and laborious procedure, requiring the availability of proper equipment and professionals with technical training in advanced laparoscopic surgery and liver surgeryMost of the studies indicate this technique for resecting benign hepatic tumors or treating hepatic cysts. The best candidates would be young patients with superficial or peripheral benign tumors with indication of limited parenchyma resection. It is also recommended that the method be employed in resections of the anterolateral portions of the liver, segments II, III, IV b, V, VI, or of the left portion of the caudate lobe. Within these criteria, the results are encouraging, with minimal morbidity and no complications such as bleeding or air embolismThe technical standardization, with use of conventional surgery technology adapted for laparoscopy is, according to Buell et al. (2005), an important aspect to facilitate the procedure. Among the new technologies available, laparoscopic ultrasound transducers should be highlighted as well as the use of hand assisted equipment, which consists of a ring set on a small skin incision of about 7 cm connected to a plastic bag, through which you can reach into the abdominal cavity without leaking gas from the pneumoperitoneum. Fong et al. (2005) reinforces that, with the use of this technology, the procedure becomes easier and safer, the confidence in obtaining safe margins is increased, and the removal of the specimen is facilitatedBleeding is the major complication and the biggest challenge intraoperatively. Most conversions to open surgery, about 70%, happen due to intraoperative bleeding. Proper patient selection, meticulous technique, and clamping methods of the hepatic pedicle can reduce this dreaded complication. Hence, vascular control is a major concern in hepatectomies, especially in resection of tumors close to large vessels or in major resections. The clamping of the hepatic pedicle, Pringle maneuver, can be done easily by placing a shoelace around the hepatic hilum, which creates a tourniquet to control the hepatic flowAnother concern is the possibility of spreading tumor cells during removal of the fragment. The specimen should always be introduced into a sturdy material bag and its removal should be done through the umbilical incision, when it has less than 3 cm, or through an appendectomy or suprapubic incision, when it is a larger piece. There is no doubt that for the treatment of benign tumors, especially liver adenomas that affect young women, laparoscopic hepatectomy has an important role. The whole debate should be reserved for cases of cancer in which laparoscopic surgery could increase the risk of neoplasic cells implantation, a fact that has not yet been demonstratedRobotics was introduced in medicine nearly two decades ago as a way of overcoming the limitations of movement of the laparoscopic instruments and providing better visualization of the surgical field. The Da Vinci station, the most used equipment for this type of surgery, was introduced in 2000. It has a three-dimensional view camera that allows a better sense of depth and is capable of more movements than the human hand is naturally capable ofIn robotic assisted surgery, the patient is placed in a supine Trendeleburg position with legs apart. Commonly, five entrance points are positioned along a semicircular arc. The procedure then follows three phases: portal dissection, liver mobilization, and parenchyma transection. The main surgeon sits in front of the robotic device as the assistant surgeon stands next to the patient’s right sideIn the first phase, the liver is retracted cephalically to expose the hilar region. The portal pedicle is dissected and its components are exposed. How the procedure will continue depends on which segment will be removed. Thus, the respective branches of the portal vein and hepatic artery are divided. The liver is mobilized after transection of the falciform and triangular ligaments, but other structures can also be sectioned depending on the procedureAfter these steps, the capsule is incised through cauterization and the hepatic trasection begins. Two robotic arms can make the transection easier by retracting the liver and opening the surgical site. The other two arms carry a device of ultrassonic dissection and a diathermic scissor. Then a titanium clip or an endostapler is positioned to clamp the main vascular branches and biliar ducts. After the parenchyma transection is complete, the surface is inspected for any bile leakage or exudation. The specimen is then obtained through a Pfannenstiel incision inside a bag called endobagRobotic technique can also occur with fluorescence guidance through application of indocyanine green that can be injected into the bloodstream and becomes fluorescent once it gets in contact with light of a specific wavelength near the infrared spectrum (around 820 nm) or a laser beam. The fluorescence can be detected inside specific rooms and chambers and then transmitted to a standard monitor that allows the identification of anatomical structures in which the dye is presentThe robotic platform has proven to be an effective tool, particularly in the urological and gynecological field. The major drawback so far are the high costs and the difficulties in providing on board training for surgeons. Many centers in the world have performed liver resections using the Da Vinci platform but only in highly selected patientsAmong laparoscopic surgeries, hepatectomies were one of the last to be carried out. The surgery was viewed with some skepticism due to concerns about bile leakage, incomplete resection, and, particularly, bleeding control, as blood loss is almost inevitable in the resection of liver tumors. Moreover, hilar dissection, liver mobilization, and parenchyma transection demand advanced technical skills and an accurate knowledge of anatomy, being, thus, potentially more dangerous than other laparoscopic proceduresDespite the many obstacles and challenges, laparoscopic hepatectomy shows numerous benefits over open hepatectomy. These are the same as in all laparoscopic surgical procedures, among which we can highlight the fact that the patient reports less pain postoperatively, has a lower incidence of ileus, less scarring, a shorter recovery time and hospital stay, and a lower rate of complicationsA case-control study conducted by Lee et al. in 2007 helps support this view since it showed that laparoscopic hepatectomy caused less blood loss, lower morbidity rate, and less overall operative complications. In another study conducted in 2009, Zhang et al. observed 78 patients who underwent laparoscopic hepatectomies. The procedure was successful in all patients, without conversion to open procedures, and only four required blood transfusions.Fonseca et al. (2003) and Machado et al. (2013) conducted studies with, respectively, 57 and 107 patients who underwent laparoscopic hepatectomies. Blood transfusion was required in 29.8% and 18.7% of patients, respectively. There was no operative mortality in both studies. The rate of postoperative complications was 57.9% in the first study and 14.9% in the second. It is clear, therefore, that there has been an advance in the art of laparoscopic hepatectomy, as the percentage of complications and the volume of blood loss have been decreasing.Alhomaidhi et al. (2012) conducted a comparative study through a literature review that showed that, between 1990 and 2010, 751 open hepatectomies and 4207 laparoscopic hepatectomies were conducted. On average, it took 65 min less to perform the laparoscopic surgery. Blood loss volume was 260 ml in patients undergoing laparoscopic hepatectomy, while the loss at laparotomy was of 1290 ml on average. Postoperative morbidity was relatively low on both operations. The length of stay and mortality were also reduced.Franken et al. (2014) conducted a comparative study of 104 patients, in which 52 underwent laparoscopic hepatectomy (group 1) and 52 underwent open hepatectomy (group 2). They noted that the estimated blood loss average was lower in patients undergoing laparoscopy (237 ml) than in those undergoing open surgery (387 ml). The average hospital stay was five days in group 1 and six days in group 2. Although blood loss decreased with laparoscopic hepatectomy, the need for blood transfusion was not significantly different and the severity of complications was not different between the groups.Koffron et al. (2007) conducted a study in which 300 laparoscopic liver resections were compared to open procedures. They noted that the laparoscopic approach was superior to the open technique. The benefits were significant in the following aspects: duration of surgery (99 vs. 182 min), blood loss (102 vs. 325 ml), need for transfusion (two out of 300 cases vs. eight out of 100 cases), hospitalization (1.9 compared to 5.4 days), overall postoperative complications (9.3 vs. 22%), and local recurrence of malignancy (2 vs. 3%).Wakabayashi et al. (2014) and Wang et al. (2015) also conducted comparative studies indicating that laparoscopic hepatectomy is better than the open technique. It was noticed that the exposure of the region is better, the hospital stay is shorter, the size of the incision and the blood loss was smaller, and the cost to the hospital is lower. Despite all these advantages, it was elucidated by Wakabayashi et al. that the restriction in the handling area is a considerable disadvantage. Wang et al. also noted that the possibility of tumor dissemination and the difficulties in maintaining adequate margins are potential disadvantages. According to Machado et al. (2012), in patients with a previously identified technical difficulty for the exclusive use of laparoscopy, hybrid techniques may be used with hand assistance or laparoscopic release followed by liver section through a small incision. The use of hand assisted techniques makes it easier to display the liver, to section the parenchyma, especially in cirrhotic livers, and also allows the surgeon the tactile sensation lost in laparoscopy. However, it is believed that a frequent use of this technique is not required, as it should be a step prior to complete conversion to laparotomy, or an option when difficulties for the realization of a total laparoscopic technique are expected.The literature review shows an exponential growth in the number of and indications for laparoscopic hepatectomies. In a review of all published cases of laparoscopic hepatectomies, held in 2009, in which 2804 cases were identified, the mortality rate was only 0.3% and morbidity 10.5%Therefore, if there is indication for a hepatectomy, provided there is no contraindication for the method , laparoscopy should be the technique of choiceWhen comparing laparoscopic and robotic techniques, in accordance with Montalti et al. (2015), it’s noticeable that, despite laparoscopy’s worldwide spread since its introduction, robotics have not had the same evolution, possibly due to the significant initial costs and the different levels of required learning. Studies show that there is no significant difference in morbidity rate between the two techniques, although it was observed a tendency for fewer complications in the robotic group.In a systematic review and meta-analysis, Montalti et al. (2015) states that the robotic platform is a tool with which many of the limitations of conventional liver laparoscopic surgery could be overcome, like image amplification, two-dimensional tremor, fulcrum effect, limited freedom of movement, and ergonomics. Furthermore, the increased dexterity activated by the endowristed movements, the filter software for the surgeon movements, and the high definition 3-D vision provided by a stereoscopic camera allows a constant and careful dissection of structures. All of this leads to minimal biliary leakage and overall reduction in postoperative complicationsDespite all these advantages, robotic assisted hepatectomy has evolved slowly over the years and it is currently unable to provide useful tools to fully exploit the potential of the movements and the vision offered by the robot, especially when the resection space is limited.It is important to note that to perform the robotic technique, an additional surgeon responsible for the procedure is required and the costs with the robot, the instrumentation, and the annual maintenance are high. In addition, there are few centers in the world that perform robotic liver resections and they always go through a thorough patient selection, which limits the number of procedures performed, and keeps it as non-standard, even if these centers can surpass the learning curve.The results of the meta-analysis made by Montalti et al. (2015) show a significant rise in bleedings during robotic assisted hepatectomies, which can be explained by the different techniques used to execute the liver transection. The most used technique for laporoscopic hepatic transection requires the use of a harmonic scalpel for superficial liver trasection and Cavitron Ultasonic Surgical Aspirator for deeper cuts, to provide a more meticulous and precise parenchymal structure dissection. In turn, in robotic resection the technique is based on crushing fixation, requiring, in most cases, the use of an intermittent occlusion of blood flow (Pringle’s Maneuver).Another important factor regards the operation time, which was significantly higher in robotic hepatectomy. This may be due to the technique itself buy may also be a result of robotics being new and requiring, therefore, greater experience and refinement.As it is known, one of the principles of oncologic resection of malignant tumors is the maintenance of free margin to avoid incomplete resection of the tumor and possible iatrogenic spread. That is why the previously mentioned meta-analysis aimed to observe the margins width in each technique. As a result, no significant difference was observed, although there was a tendency for smaller margins in laparoscopic hepatectomies, which suggests a greater difficulty in identifying the lesion through robotic intraoperative ultrasound. This can be explained by the fact that the surgeon who performs the ultrasound is not the one responsible for the robotic hepatectomy. However, further studies are necessary for a better data analysis. The study of Montalti et al. (2015) considers that laparoscopic hepatectomies have a reduced blood loss and a shorter operative time compared to robotic hepatectomies.Thus, it is not clear whether robotic assistance demonstrates substantial advantage over laparoscopic techniques since both approaches are considered minimally invasive, with no differences in safety or efficacyThe approach of liver tumors is considered complex as it involves factors related to the clinical condition of the patient, the function of the liver, and the stage and characteristics of malignant diseases. Some tumors develop in livers considered normal, while others arise in organs compromised by obstruction of the biliary tract or liver diseases such as steatosis, fibrosis, or cirrhosis. Each of these factors can influence the result of surgeries and, therefore, careful attention to all of these aspects must be paid in order to achieve good results. The laparoscopic approach is more beneficial when compared to the open technique, despite the barriers and mistrust that still remains. Laparoscopy has shorter procedure duration, shorter hospital stay, and lower incidence of complications. Furthermore, the local malignant recurrence rate is also reduced in the closed surgical procedure.When laparoscopic and robotic techniques are compared, it is clear that the robotic assistance can overcome many limitations that laparoscopic surgery presents. However, due to the high cost and different levels of learning required, robotic hepatectomy still hasn’t spread worldwide. It is not yet clear whether robotic assistance is an advantage over laparoscopy, since hospital stay, morbidity, and estimated blood loss are similar.


Lehoux et al provide a highly valid contribution in conceptualizing value in value propositions for new health technologies and developing an analytic framework that illustrates the interplay between health innovation supply-side logic (the logic of emergence) and demand-side logic . This commentary brings forth several considerations on this article. First, a detailed stakeholder analysis provides the necessary premonition of potential hurdles in the development, implementation and dissemination of a new technology. This can be achieved by categorizing potential stakeholder groups on the basis of the potential impact of future technology. Secondly, the conceptualization of value in value propositions of new technologies should not only embrace business/economic and clinical values but also ethical, professional and cultural values, as well as factoring in the notion of usability and acceptance of new technology. As a final note, the commentary emphasises the point that technology should facilitate delivery of care without negatively affecting doctor-patient communications, physical examination skills, and development of clinical knowledge. The authors also highlight, through the literature, qualitative research and discussion, the multifactorial complexities and challenges involved in balancing the innovation policy, namely the supply side logics as determined by financial markets and business media, and the health policy demand-side logics that include health technology assessment, reimbursement and procurement. The authors however acknowledge, “New technologies constitute an important cost-driver in healthcare, but the dynamics that lead to their emergence remains poorly understood…” (p. 1).Lehoux et al provide a highly valid contribution in conceptualizing value in value propositions for new health technologies and developing an analytic framework that illustrates the interplay between health innovation supply-side logic (the logic of emergence) and demand-side logic .In this commentary, we would like to put forward several points, as part of the commentary of this article.2 Holtkamp et al,3 and van Hoof & Verkerk4 have come up with various frameworks for the incorporation of technology philosophy in order to help identify and map the needs of patients (and other stakeholders) within different user contexts. Such frameworks, however, do not deny the complexity of the intertwined world of stakeholder needs. In particular, for technologies that are still to be made available, defining all the potential stakeholders is challenging. Moreover, in terms of user acceptance, consulting potential end-users during the pre-implementation phase of new technologies can lead to skewed representations towards the usefulness of such devices that would have been more mature and crystallised if people had the chance to experience and engage with the devices in question.5 Therefore, it is important to envisage the potential impact of future technology, and this entails primarily categorizing potential stakeholder groups that could be affected, as well as recognising the differences between pre- and post-implementation research.6Lehoux et aldecided to focus on three key stakeholders in their study. Although entrepreneurs involve clinical teams to provide valuable information regarding patient needs and health benefits of new technologies, capital investors look out for business opportunities of innovations to curb down health risks of extant technologies or clinical practice, and regulatory agencies aim towards achieving patient safety, and the efficacy and quality of technology, the minimally consulted users/patients/clients often have to take what is on offer without a choice for alternatives. In addition, the client system revolving around the patient, in particular the informal caregiver is often overlooked. In the delivery of healthcare services and technologies, the patient should be the focus of attention. Van Hoof et al,6 A robust stakeholder analysis provides the necessary premonition of potential hurdles in the development, implementation and dissemination of a new technology. A comprehensive analysis will more likely guide the course of development of technology early on, while considering affected stakeholders and the wider community.7A suggested approach is using temporal stakeholder and event analysis, which transfers learning from different stakeholder groups’ experiences with previous technologies, to new technologies or systems. This analysis provides a structure that captures the lifecycle of technologies and outlines the impact on different stakeholder groups at each stage of the lifecycle.8 On many occasions, the client’s consent is taken for granted. The example of the home telehealth solution reveals that the chronically ill and older adults, potentially identified at the end of the process, are accidental stakeholders.8On the other hand, the identification of too many stakeholders may be problematic in that these have specific interests that may separately or collectively impede the implementation of new technology, regardless of the clients’ intentions.1 The article also refers to investors, who because of their desire for a quick return on investment, and their aim to bring the venture to the most profitable exit, will only provide support for a limited period of time despite evidence of patient benefits and value creation for health systems.The manner in which the three key stakeholders mentioned in the study define value is a clear reflection of the often-limited business/economic focus adopted. The examples of innovations in the article alert us of this limitation and invite us to consider a broader and more comprehensive conceptualization of value in value propositions of new technologies. Additionally, the qualitative study highlights the vested interests of the three stakeholders, and therefore the fragmented manner in which value is conceptualized. For example, the authors lament, “Investors support technologies that generate health gains by accident, not by design.”Entrepreneurs, who tap on their healthcare experience, seem to have a more balanced consideration of not only having the proposed technology generating revenues but also a capacity to generate health benefits and therefore do have a patient focus. The regulatory agencies also have a somewhat specific remit, namely that of focusing on safety and efficacy of new technologies relying on science, expertise and judgment when executing appraisals. While the values defined are of critical consideration, we propose stakeholders to collectively consider ethical concepts apart from the business/economic and clinical values that are described in more detail below.9 Technology is considered to influence various human experiences, amongst them health.10 Although it influences social changes, and could be a source of power, vulnerability, and inequality, new technologies are still too often introduced with little critical reflection on their impacts.10 This is of particular concern in healthcare when the problematic allocation of scarce resources should leave little room for experimentation in view of the ever-rising healthcare costs and health inequalities.The first that comes to mind are the ethical values and aspects when proposing and considering new technologies.11 In particular, professionals delivering chronic care value inter-collegial respect. Additionally, clinicians do not relate technological solutions for clinical problems. Therefore, for success in the implementation of new technologies, it is essential that these values are not disrupted and that clinicians should receive solid support and education to effectively link technological solutions to care recipients’ needs.11The second concept is the consideration of professional values of healthcare professionals, whose main goal is their ability to satisfy the needs of their patients and clients.12 See, for instance, Moors and Peine,13 who discussed how to value health innovations within a broader socio-cultural context. Therefore, stakeholders should also consider the social and cultural aspects of technology in its design, implementation and dissemination.12The third concept is the consideration of the social and cultural values of the value proposition. The extent to which a technology is effective in the world does not only depend on its technical aspects but also on how successful it is to match the social and ecological contexts where it is implemented.8 If a new technology satisfies three properties, namely effectiveness, efficiency and satisfaction, then it is more likely to be high on usability. Additionally, memorability and learnability are also considered important.8The fourth concept is the consideration of usability, ie, user-oriented approach, which is considered an important determinant of acceptance.13New technologies, if introduced successfully, will always to some extent disrupt existing ethical, professional or cultural practices. This encompasses more than just meeting user needs or professional values. There will always be socio-material practices that arise during the implementation, which are the “locale” in which old values are contested and new values arise. These emerging and evolving values are critical in assessing a technology and determining its “success.” The distinction between a prosthetic logic  and a habilitating logic  might help in this regard.14 Winner argues, “The capacity and willingness to reflect on the significance of technology and to critically evaluate new technologies lags far behind our capacity for creating and disseminating technologies” (p. 48).14 Unless a more robust assessment is used that encompasses the biopsychosocial model of care, new technologies pose numerous challenges in the various stages from the development to adoption and subsequent sustainability of the uptake.The focus of technological assessments tends to be mostly on the positive and negative impacts or effects of a technology without much consideration of the manner with which they restructure our physical and social worlds.15 A potential side effect of the increased usage of technology in healthcare is the rise in costs that may hamper the overall accessibility of cure and care services, both from a patient and a professional perspective. Indeed, since clinicians are becoming more dependent on technology, in particular for accessing patient information, reaching diagnoses and delivering care, undergraduate and professional development training on using medical technology in the domains of cure and care has become a must to ensure autonomy while interfacing with medical technology.15In this commentary, we have highlighted only some aspects of how new health technologies can provide greater value to end-users and to society as a whole. The subject area is complex, challenging and continues to confound leaders of health systems. Our commentary is intended to shed more light on what Lehoux et al masterfully provided in their study. As a final note, we believe that technology should facilitate the delivery of care without negatively affecting doctor-patient communications, physical examination skills, the perception of safety and security among patients, and the development of clinical knowledge.Not applicable.Authors declare that they have no competing interests.SCB and JvH have discussed the outline for the paper. SCB has drafted the paper, which JvH has critically read and amended. Both SCB and JvH have revised after receiving reviewers’ feedback.1Faculty of Health Sciences, University of Malta, Msida, Malta. 2School of Social Policy, College of Social Sciences, University of Birmingham, Birmingham, UK. 3Institute of Allied Health Professions, Fontys University of Applied Sciences, Eindhoven, The Netherlands.


The importance of strong engagement between researchers and decision-makers in the improvement of health systems is increasingly being recognised in low- and middle-income countries (LMICs). In 2013, in India, the Ministry of Health and Family Welfare began exploring the formation of a National Knowledge Platform (NKP) for guiding and supporting public health and health systems research in the country. The development of the NKP represents an important opportunity to enhance the linkage between policy-makers and researchers from the health policy and systems research field in India. However, the development process also reflects the highly complex reality of policy-making in the Indian health sector. Our objective is to provide insight into the policy-making process for establishing a health sector knowledge platform in India, and in doing so, to analyse the enabling contextual factors, the interests and actions of stakeholders, and the varying institutional arrangements explored in the development of the NKP.We used a qualitative case study methodology, conducting 16 in-depth interviews and reviewing 42 documents. We utilised General Thematic Analysis to analyse our data. Our research team combined perspectives from both outsiders (independent researchers with no prior or current involvement with the policy) and insiders (researchers involved in the policy-making process).We found that enabling contextual factors, and a combination of government and non-governmental stakeholders with core interests in public health and health systems, were able to gain considerable momentum in moving the idea for the NKP forward. However, complex evidence-to-policy processes in the Indian health sector resulted in complications in determining the right institutional arrangement for the platform. Establishing the appropriate balance between legitimacy and independence, as well as frequent changes in institutional leadership, were found to be additional issues that stakeholders contended with in building the NKP.As interest in platforms linking health sector policy-makers and researchers grows in LMICs, our findings may allow stakeholders to learn from the Indian experience thus far, and to anticipate some of the facilitators and barriers that could potentially arise in establishing such mechanisms. The importance of strong engagement and learning between researchers and decision-makers in the improvement of health systems is increasingly being recognised in low- and middle-income countries (LMICs) –3. A varRecently, momentum has been growing in several LMICs to establish, expand and strengthen these platforms , 6–8. InEvidence from India suggests a growing movement towards strengthening linkages between researchers and decision-makers in the context of health policy and systems research (HPSR) , 12. StaTo address these gaps, in 2013, the Indian Ministry of Health and Family Welfare began to explore the formation of a National Knowledge Platform (NKP) for guiding and supporting public health and health systems research in the country (Box 1). Formalised in 2016, the NKP is meant to systematise dialogue between researchers and research users, to provide funding support for public health and health systems research in priority areas, and to support capacity-building and knowledge management , 17. OthThe policy-making process for the NKP presented several interesting questions pertaining to both the issues faced by stakeholders in initiating such a platform and the complex reality of policy-making in the Indian health sector . ExaminiWe selected a descriptive analytical case study for our study design due to its utility in gathering rich, context-specific data on contemporary, complex phenomena , 20. A smultifacted, durable social structures, made up of symbolic elements, social activities, and material resources”  willing to listen. And therefore it was a fairly happy amalgamation of people with convergent perspectives but coming from different directions.” (Domestic Researcher)“In 2013, MoHFW officials were introduced to the idea of a formal mechanism or knowledge platform during a meeting of Indian researchers who had attended the Beijing Global Health Systems symposium in November 2012 . PHFI had been designated as a Nodal Institute for AHPSR in India in 2012 , and in Simultaneously, interest was growing within PHFI around strengthening the linkage between evidence and policy. Between May 2013 and August 2013, PHFI researchers, with strong support from AHPSR, began pursuing the ideas raised at the meeting convened by MoHFW , and developed proposals for a mechanism to link researchers and decision-makers. Ideas were explored with key stakeholders, including MoHFW and leadership at NHSRC .A second, smaller meeting was held in August 2013, following which PHFI took the lead in following up on the window of opportunity presented by the Secretary  . PHFI submitted a proposal for the platform, now formally termed the NKP, in December 2013. In early drafts, the NKP was largely administered by PHFI. The Secretary largely agreed with the configuration, and importantly, initiated a file in December 2013. However, the policy process received a setback when the Secretary was transferred in February 2014.The changes in leadership at MoHFW between January 2014 and May 2014 resulted in inactivity regarding the NKP. The new Secretary (MoHFW) affirmed his interest in the platform, and a new round of discussions began between MoHFW, PHFI and NHSRC in late 2014 . The leadership at NHSRC had also changed in March 2014, and the new Executive Director became interested in the idea of NHSRC playing a central role in the NKP. By early 2015, NHSRC had emerged as the preferred option for convening the platform, with PHFI still playing a role in organising one sub-committee (D33). However, the Secretary was once again transferred and replaced in February 2015; however, this time, discussions had sufficiently progressed at MoHFW to provide momentum to the policy process.Periodic discussions between MoHFW, NHSRC and PHFI were held from January to June 2015, but did not result in formal action. A change in leadership at ICMR/DHR in August 2015 appeared to reinvigorate a discussion around the platform. The new leader of ICMR wanted to enhance the role of ICMR and DHR in supporting the linkage between research and policy-making. Once again, the possible leadership configuration of the NKP began to shift as the new ICMR leader believed that ICMR/DHR could play a convening role in the NKP.One of the most significant changes in the scope of the platform over time was a suggestion by MoHFW in January 2015 to broaden the scope beyond health systems research to encompass public health research. The proposed functions of the NKP have largely stayed intact from the initial stages of policy formulation .The arrangement of the proposed platform evolved from the early discussions in mid-2013, to its current format “Early on, some stakeholders felt that an embedded unit within MoHFW could ensure traction of research with decision-makers .…Where is the independence of that? Secondly, they may not be able to speak up with boldness to the decision makers. I mean, speaking truth to power is difficult if you are actually getting your salary from there.” (Domestic Researcher)“However, one participant noted that there was a sense within MoHFW that they might not have the capacity to house the structure internally (I6), while another participant mentioned a possible lack of bandwidth to pursue the idea within MoHFW due to other priorities (I1). A further stakeholder argued that the platform would be easier to manage if externally located, compared to the intensive effort required to make permanent changes to the bureaucracy (I15). Stakeholders also expressed a tension between ensuring independence but remaining credible and legitimate. Some researchers noted that the NKP needed to have an ‘arm’s length’ relationship with the Government in order to have independence and objectivity , similar to health sector evidence-to-policy mechanisms in Thailand such as the International Health Policy Programme . One participant shared the following concern of embedding a unit within MoHFW:Embedded…you sort of become, you think like the Government. You become more political, you become more administrative and you forget the unbiased nature of research…Embedded also means that your agenda is always the implementation agenda.” (Domestic researcher)“Another researcher participant similarly noted:…the Government never feels comfortable with anything that it cannot control or at least own. So in that sense, it would like at least one of its agencies to be actively engaged…” (Domestic researcher)“Conversely, policy-makers and one researcher expressed the need to balance ownership and buy-in from MoHFW and ensure that the findings are appropriately considered and utilised .In the period between August and December 2013, the idea for the platform evolved from a physically embedded unit to a more independent platform, a conceptualisation proposed by PHFI . Several participants noted that an independent structure with government association would be the ideal home for such a platform. Over the course of 2014 and 2015, the independent nature of the platform stayed intact; however, various additional committees and groups were considered as part of the design, including a Scientific Advisory Committee, an Executive Council (a sub-committee of the Steering Committee), a Grant-in-Aid committee, and Technical Resource Groups. However, some stakeholders reportedly became uncomfortable with the increasing complexity of the NKP as the proposal evolved, and suggested streamlining the structure (D37).Once the NKP evolved to be an independent platform outside of MoHFW, possible administrative control ‘wandered’ between PHFI, NHSRC and ICMR (I11). PHFI and NHSRC in particular discussed at length the role of each institution in administering the platform . Some of these changes were due to the leadership changes at these institutions, and the perspectives of incoming leaders regarding the preferred role for their institution in the platform.Another debate was regarding whether the Chairmanship of the Scientific Advisory Committee should be permanently given to PHFI or rotated across institutions periodically (D5). The proposed arrangement of PHFI permanently retaining the Chairmanship of the Scientific Advisory Committee was facilitated primarily by the early and ongoing interest in MoHFW in having PHFI play that role (D5). However, a few stakeholders outside PHFI expressed concerns about the conflict of interest with PHFI’s involvement given their prominent role in the country as researchers and, therefore, potential beneficiaries of research funding from the platform . Some stakeholders made MoHFW aware of their perceived need for stronger conflict of interest mechanisms. Guiding documents for the Government Order formalising the NKP continued to formally state that individuals involved in any selection process must formally recuse themselves from decision-making where they have a conflict of interest .Following data collection, a decision was taken by MoHFW for NHSRC to become the Secretariat, and PHFI to convene the Scientific Advisory Committee . ICMR woAs discussions progressed, stakeholders actively debated some key cross-cutting issues.The level of leadership of the platform was a key point of negotiation. In early versions of the NKP, the operational leadership of the mechanism was centred at the Secretary level . One participant reasoned that, while Secretaries may not be involved operationally, their buy-in to the NKP was critical (I16). In other iterations, leadership was pegged at the Additional Secretary level , and in the final format, was once again elevated to the Secretary level (D40).…first is to establish what the mandate is clearly, and then decide what the functions of this core are and how they are going to be shared around in a complementary manner between the various partners. Then you can reach out to others. If you reach out to others without having the confusion sorted out, then you are not going carry conviction to others, you are only going to disseminate the confusion and either put them off or bring them into a non-productive process.” (Domestic Researcher)“Stakeholders wrestled with how to best engage the numerous institutions involved in evidence-to-policy in the Indian health sector. One participant described the need to work out the mandate and structures, before involving other people and institutions.The formation of a knowledge translation platform focused on public health and health systems research in India was a result of a unique convergence of several factors. At the national level, various policies and reforms in the 2000s and early 2010s, most notably the initiation of NRHM in 2005, primed the Government to support a health sector knowledge platform. National and international context intertwined, with increasing global attention to HPSR in the early 2010s, and in the growing emphasis within WHO and other international health sector stakeholders on strengthening linkages between policy-makers and researchers, two factors strongly articulated in the 2012 WHO strategy on HPSR. Shaped and driven by this context, PHFI and AHPSR emerged in 2012–2013 as ‘institutional entrepreneurs’, working synergistically to establish a new KTP for health policy and systems that would address perceived lacunae in knowledge translation between policy-makers and researchers working in the health sector . Their eThe policy process to develop the NKP appears to reflect some of the underlying struggles in developing a KTP of this nature, as well as in policy-making in the Indian health sector more broadly. Our analysis of the development of the NKP suggests three areas that illuminate these issues.Complexity of the decision-making architectureThe complexity of the decision-making architecture in the Indian health sector, and particularly in the realm of linking evidence to policy, was a key challenge in the development of the NKP. The NKP represented a systemic shift in how government and researchers interact and, therefore, necessitated broad stakeholder engagement in its evolution. Yet, the number of institutions in India with some evidence-to-policy mandate, and the frequency of leadership transitions within those institutions, resulted in a complicated policy landscape, one in which policy-making and governance on this issue became challenging.Such difficulties in governance in the Indian health sector have been widely discussed in the literature and anecdotally. Patel et al.  have notBalancing independence and legitimacyno single, optimal, institutional distance between a [health policy analysis institute] and its target audience”. This ambiguity actively played out with the NKP, with the locus for convening moving between four institutions, namely MoHFW, PHFI, NHSRC and ICMR.The objective of establishing a knowledge platform such as the NKP is to ensure that the mechanism is actively used and trusted by the government – this requires that the institution that has administrative control over the mechanism have credibility and legitimacy in the eyes of the government, which might only be possible with an institution that they feel some ownership over. However, ownership actively contends with another objective of these mechanisms – independence – and a key challenge is balancing these two concepts, without diminishing the value of the platform . The varThe Secretary (MoHFW) at the time felt there was a place for an in-house mechanism within the architecture of MoHFW. However, even with committed leadership, establishing such a platform can be logistically difficult, given the array of issues facing policy-makers. Setting up such a mechanism would also require a broader base of support within MoHFW. Both El-Jardali et al.  and BermHowever, the weaknesses of a government-based approach discussed by El-Jardali et al.  and CampOne way to enhance the independence of the mechanism is to establish strong conflict of interest mechanisms within the structure. Such mechanisms were also proposed by Bennett et al.  in theirPersonalised leadership and networksMany participants highlighted the primacy of bureaucrats in policy-making in India, and the role of the Secretary (MoHFW) in this study is an excellent illustration of that point. However, as noted in other studies , 33, theThe importance of individuals and personal relationships in influencing policy  is a ‘double-edged sword’ as influence can wane if those individuals leave the organisation . Koon etWe note some limitations to this study. First, policy formulation was not yet complete by the time data collection ended and we were therefore unable to explore the formulation process in totality. Second, MoHFW officials were hesitant to be interviewed in late 2015 as policy discussions were still ongoing, resulting in an inability to incorporate these viewpoints in our analysis. We addressed this issue by speaking with a former MoHFW official and with current central government officials who were all involved in the policy process. Third, our sample was weighted towards participants who were researchers, potentially influencing our analysis; we sought to overcome this challenge by recruiting researchers who worked closely with government on policy development and could therefore provide further insight regarding internal policy discussions. Fourth, some of our participants were peripherally aware of the development of the NKP, and therefore could only comment substantively on the context and their perceptions of the actors involved, and not on the process or the content of the platform.The development of the NKP in India represents a unique opportunity to institutionally enhance and strengthen the linkages between researchers and decision-makers in the health sector. Our analysis finds that enabling contextual factors, and a combination of government and non-governmental stakeholders with core interests in public health and health systems, were able to gain considerable momentum in moving this agenda forward. However, the complex evidence-to-policy process in the Indian health sector resulted in complications to determining the right institutional arrangement for the platform. Determining the appropriate balance between legitimacy and independence, and the frequent leadership changes of the key stakeholders involved, also shaped the development of the platform. As more initiatives to strengthen linkages between researchers and policy-makers emerge in LMICs, we hope that the findings of this study support stakeholders in understanding possible trajectories of their efforts, and to anticipate some of the facilitators and barriers that they might experience in developing these mechanisms.1) Enabling regular and productive knowledge sharing and dialogue between public health and health systems researchers and research users (policy-makers and implementers) at state and national levels2) Support for public health and health systems research in priority areas through grant funding in annually identified priority thematic areas – comprising competitive research grant call; commissioned research in response to specific knowledge requirements and conference scholarships3) Facilitation of research uptake and dissemination4) Research capacity-building5) Knowledge management on an open-access platform